angiotensin converting enzyme 2

Gene Context Sentence

Table 2. Analysis of context sentence of ACE2 gene in 2065 abstracts.

PMID Gene Context Sentence
31996437 Since the SARS-CoV outbreak in 2002, extensive structural analyses have revealed key atomic-level interactions between the SARS-CoV spike protein receptor-binding domain (RBD) and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-to-human transmissions of SARS-CoV. […] First, the sequence of 2019-nCoV RBD, including its receptor-binding motif (RBM) that directly contacts ACE2, is similar to that of SARS-CoV, strongly suggesting that 2019-nCoV uses ACE2 as its receptor. […] Second, several critical residues in 2019-nCoV RBM (particularly Gln493) provide favorable interactions with human ACE2, consistent with 2019-nCoV’s capacity for human cell infection. […] Third, several other critical residues in 2019-nCoV RBM (particularly Asn501) are compatible with, but not ideal for, binding human ACE2, suggesting that 2019-nCoV has acquired some capacity for human-to-human transmission. […] Last, while phylogenetic analysis indicates a bat origin of 2019-nCoV, 2019-nCoV also potentially recognizes ACE2 from a diversity of animal species (except mice and rats), implicating these animal species as possible intermediate hosts or animal models for 2019-nCoV infections. […] Our decade-long structural studies on the receptor recognition by SARS-CoV have identified key interactions between SARS-CoV spike protein and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-to-human transmissions of SARS-CoV.
32015507 Notably, we confirmed that 2019-nCoV uses the same cell entry receptor-angiotensin converting enzyme II (ACE2)-as SARS-CoV.
32022370 Herein, we suggest four potential drug candidates (an ACE2-based peptide, remdesivir, 3CLpro-1 and a novel vinylsulfone protease inhibitor) that could be used to treat patients suffering with the 2019-nCoV.
32023682 According to current observations, 2019-nCoV is weaker than SARS in pathogenesis, but has stronger transmission competence; it’s mechanism of cross-species spread might be related with angiotensin-converting enzyme Ⅱ (ACE2), which is consistent with the receptor SARS-CoV. […] 目前数据表明:2019-nCoV比SARS-CoV毒力弱,但传播力强;造成其能够跨种传播的受体可能与SARS-CoV一致,都是血管紧张素转化酶Ⅱ(ACE2)。
32061198 The novel coronavirus 2019 (COVID-19) infected patients by binding human ACE2, leading to severe pneumonia and highly mortality rate in patients. […] ACE2 plays an important role in the RAS, and the imbalance between ACE/Ang II/AT1R pathway and ACE2/Ang (1-7)/Mas receptor pathway in the RAS system will lead to multi-system inflammation. […] The binding of COVID-19 and ACE2 resulted in the exhaustion of ACE2, and then ACE2/Ang (1-7)/Mas receptor pathway was inhibited. […] 新型冠状病毒通过与人体血管紧张素转化酶2(ACE2)结合感染产生重症肺炎,传染性强,病死率高,目前无确切有效的治疗方式。 […] ACE2是肾素-血管紧张素系统(RAS)的重要组成部分,RAS系统中ACE/Ang II/AT1R通路与ACE2/Ang (1-7)/Mas受体通路失衡将导致多系统炎症。 […] 新型冠状病毒与ACE2的结合导致ACE2耗竭,ACE2/Ang (1-7)/Mas受体通路受到抑制,RAS系统失衡,使新型冠状病毒肺炎患者病死率升高。
32065055 The epitope of CR3022 does not overlap with the ACE2 binding site within 2019-nCoV RBD. […] Interestingly, some of the most potent SARS-CoV-specific neutralizing antibodies (e.g. m396, CR3014) that target the ACE2 binding site of SARS-CoV failed to bind 2019-nCoV spike protein, implying that the difference in the RBD of SARS-CoV and 2019-nCoV has a critical impact for the cross-reactivity of neutralizing antibodies, and that it is still necessary to develop novel monoclonal antibodies that could bind specifically to 2019-nCoV RBD.
32075877 We also provide biophysical and structural evidence that the 2019-nCoV S protein binds angiotensin-converting enzyme 2 (ACE2) with higher affinity than does severe acute respiratory syndrome (SARS)-CoV S.
32077659 ACE2 expression in liver tissue for novel coronavirus was analyzed based on single cell sequencing (GSE115469) data. […] RNA-Seq method was used to analyze Ace2 expression and transcription factors related to its expression in liver tissues at various time-points after hepatectomy in mouse model of acute liver injury with partial hepatectomy. t-test or Spearman rank correlation analysis was used for statistical analysis. Results: ALT and AST were abnormally elevated in some patients with novel coronavirus infection, and the rate and extent of ALT and AST elevation in severe NCP patients were higher than those in non-severe patients. […] Liver tissue results of single cell sequencing and immunohistochemistry showed that ACE2 was only expressed in bile duct epithelial cells of normal liver tissues, and very low in hepatocytes. […] In a mouse model of acute liver injury with partial hepatectomy, Ace2 expression was down-regulated on the first day, but it was elevated up to twice of the normal level on the third day, and returned to normal level on seventh day when the liver recovered and hepatocyte proliferation stopped. […] Whether this phenomenon suggests that the bile duct epithelial cells with positive expression of Ace2 participate in the process of liver regeneration after partial hepatectomy deserves further study. […] In RNA-Seq data, 77 transcription factors were positively correlated with the expression of ACE2 (r > 0.2, FDR < 0.05), which were mainly enriched in the development, differentiation, morphogenesis and cell proliferation of glandular epithelial cells. Conclusion: We assumed that in addition to the over activated inflammatory response in patients with NCP, the up-regulation of ACE2 expression in liver tissue caused by compensatory proliferation of hepatocytes derived from bile duct epithelial cells may also be the possible mechanism of liver tissue injury caused by 2019 novel coronavirus infection. 目的: 探索和分析新型冠状病毒感染肺炎(NCP)患者发生肝损伤的可能机制。 […] 方法: 综合分析已报道文献中NCP患者的丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)等肝酶变化情况与疾病状态的相关性;基于肝组织单细胞测序数据(GSE115469)分析新冠病毒受体血管紧张素转换酶2(ACE2)在肝组织中的表达;采用RNA-seq方法分析半肝切除急性肝损伤小鼠模型肝切除后不同时间点残肝组织中Ace2的表达及与其表达相关的转录因子。 […] 肝组织单细胞测序和免疫组织化学检测结果显示,ACE2在正常肝组织中只在胆管上皮细胞表达,而在肝细胞中表达极低。 […] 在小鼠半肝切除急性肝损伤模型中,Ace2在术后第1天的急性损伤期表达下调,但在术后第3天的肝细胞增殖高峰期表达升高至正常水平的2倍以上,并在肝脏恢复、肝细胞增殖停止的第7天恢复到正常水平。 […] 这一现象是否提示ACE2表达阳性的胆管上皮细胞参与了部分肝切除后的肝再生过程,值得进一步的研究。 […] RNA-seq数据中有77个转录因子与Ace2表达呈正相关(r > 0.2,FDR < 0.05),主要富集在腺体腔管表皮细胞的发育、分化、形态生成以及细胞增殖等功能。 […] 结论: 除了NCP患者过度激活的炎症反应可导致肝损伤外,胆管上皮细胞来源肝实质细胞的代偿性增生所致病毒受体ACE2在肝组织中的表达上调,可能是新型冠状病毒感染肝细胞造成肝组织损伤的可能机制。.
32081428 Molecular modeling revealed that 2019-nCoV RBD has a stronger interaction with angiotensin converting enzyme 2 (ACE2). […] A unique phenylalanine F486 in the flexible loop likely plays a major role because its penetration into a deep hydrophobic pocket in ACE2. […] ACE2 is widely expressed with conserved primary structures throughout the animal kingdom from fish, amphibians, reptiles, birds, to mammals. […] Structural analysis suggests that ACE2 from these animals can potentially bind RBD of 2019-nCoV, making them all possible natural hosts for the virus. 2019-nCoV is thought to be transmitted through respiratory droplets. […] However, since ACE2 is predominantly expressed in intestines, testis, and kidney, fecal-oral and other routes of transmission are also possible. […] Finally, antibodies and small molecular inhibitors that can block the interaction of ACE2 with RBD should be developed to combat the virus.
32094336 It has been reported that ACE2 is the main host cell receptor of 2019-nCoV and plays a crucial role in the entry of virus into the cell to cause the final infection. […] RNA-seq profiling data of 13 organ types with para-carcinoma normal tissues from TCGA and 14 organ types with normal tissues from FANTOM5 CAGE were analyzed in order to explore and validate the expression of ACE2 on the mucosa of oral cavity. […] Further, single-cell transcriptomes from an independent data generated in-house were used to identify and confirm the ACE2-expressing cell composition and proportion in oral cavity. […] The results demonstrated that the ACE2 expressed on the mucosa of oral cavity.
32094589 We also demonstrate how different lineage B viruses can recombine to gain entry into human cells, and confirm that human ACE2 is the receptor for the recently emerging SARS-CoV-2.
32100877 In this study, we used systematic comparison and analysis to predict the interaction between the receptor-binding domain (RBD) of coronavirus spike protein and the host receptor, angiotensin-converting enzyme 2 (ACE2). […] The interaction between the key amino acids of S protein RBD and ACE2 indicated that, other than pangolins and snakes, as previously suggested, turtles (Chrysemys picta bellii, Chelonia mydas, and Pelodiscus sinensis) may act as the potential intermediate hosts transmitting SARS-CoV-2 to humans.
32117569 The proposal is a biologic that blocks 2019-nCoV entry using a soluble version of the viral receptor, angiotensin-converting enzyme 2 (ACE2), fused to an immunoglobulin Fc domain, providing a neutralizing antibody with maximal breath to avoid any viral escape, while also helping to recruit the immune system to build lasting immunity. […] The sequence of the ACE2-Fc protein is provided to investigators, allowing its possible use in recombinant protein expression systems to start producing drug today to treat patients under compassionate use, while formal clinical trials are later undertaken.
32127517 The 2019-nCoV was different from SARS-CoV, but shared the same host receptor the human angiotensin-converting enzyme 2 (ACE2).
32129518 This idea is based on observations that the angiotensin-converting enzyme 2 (ACE2) very likely serves as the binding site for SARS-CoV-2, the strain implicated in the current COVID-19 epidemic, similarly to strain SARS-CoV implicated in the 2002-2003 SARS epidemic.
32132184 Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for severe acute respiratory syndrome-coronavirus (SARS-CoV) and the new coronavirus (SARS-CoV-2) that is causing the serious coronavirus disease 2019 (COVID-19) epidemic. […] Here, we present cryo-electron microscopy structures of full-length human ACE2 in the presence of the neutral amino acid transporter B0AT1 with or without the receptor binding domain (RBD) of the surface spike glycoprotein (S protein) of SARS-CoV-2, both at an overall resolution of 2.9 angstroms, with a local resolution of 3.5 angstroms at the ACE2-RBD interface. […] The ACE2-B0AT1 complex is assembled as a dimer of heterodimers, with the collectrin-like domain of ACE2 mediating homodimerization. […] The RBD is recognized by the extracellular peptidase domain of ACE2 mainly through polar residues.
32138266 Both viruses utilize the same receptor-angiotensin-converting enzyme 2 (ACE2)-for invading human bodies.
32141569 Studies suggest that the human receptor for COVID-19 may be angiotensin-converting enzyme 2 (ACE2) receptor similar to that of SARS-CoV.
32142651 Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming.
32149769 Whether GX_P2X uses angiotensin-converting enzyme 2 (ACE2) as the cell receptor was investigated by using small interfering RNA (siRNA) -mediated silencing of ACE2. […] The spike protein of coronavirus GX_P2V shares 92.2% amino acid identity with that of 2019-nCoV isolate Wuhan-hu-1, and uses ACE2 as the receptor for infection just like 2019-nCoV.
32155444 We show that SARS-CoV-2 S uses ACE2 to enter cells and that the receptor-binding domains of SARS-CoV-2 S and SARS-CoV S bind with similar affinities to human ACE2, correlating with the efficient spread of SARS-CoV-2 among humans.
32159318 与严重急性呼吸系统综合征冠状病毒(SARS-CoV)一样,2019新型冠状病毒(2019-nCoV)亦是以血管紧张素转化酶2(ACE2)为受体感染细胞。 […] ACE2作为肾素-血管紧张素系统(RAS)的重要成员,与ACE互为拮抗,二者的平衡与失衡在维护心血管系统生理功能、机体炎症反应、肺损伤等过程中均发挥着重要作用,而其在冠状病毒感染与致病机制中亦发挥着非常重要的作用。 […] 目前为止,在7种人畜共患的冠状病毒中有3种以ACE2为受体感染细胞,即SARS-CoV、人类冠状病毒NL63(HCoV-NL63)和2019-nCoV,了解这些病毒与ACE2的相互作用对于冠状病毒感染的预防和治疗意义重大。 […] 本文对相关文献进行了梳理,总结了ACE2及RAS系统在冠状病毒感染、致病过程中发挥的作用,对于2019-nCoV防治过程中存在的争议进行了归纳,针对ACE2和RAS系统中可能存在的2019-nCoV的治疗靶点进行了展望。.
32164092 The novel coronavirus 2019 (COVID-19) infected patients by binding human ACE2, leading to severe pneumonia and highly mortality rate in patients. […] ACE2 plays an important role in the RAS, and the imbalance between ACE/Ang II/AT1R pathway and ACE2/Ang (1-7)/Mas receptor pathway in the RAS system will lead to multi-system inflammation. […] The binding of COVID-19 and ACE2 resulted in the exhaustion of ACE2, and then ACE2/Ang (1-7)/Mas receptor pathway was inhibited.
32166940 血管紧张素转化酶2(ACE2)作为受体介导2019-nCoV进入细胞,是目前最有可能防治COVID-19的靶点之一。 […] ACE2是肾素-血管紧张素系统重要的组成部分,以此系统为靶点的ACE抑制剂和血管紧张素受体阻断剂等药物,是目前临床治疗高血压、心肌重构和心力衰竭等心血管疾病的最主要的药物之一。
32167153 It has been known since the 2003 SARS epidemic that the receptor critical for SARS-CoV entry into host cells is the angiotensin-converting enzyme 2 (ACE2). […] The S1 domain of the spike protein of SARS-CoV attaches the virus to its cellular receptor ACE2 on the host cells. […] We thought that it is timely to explain the connection between the SARS-CoV, SARS-CoV-2, ACE2 and the rationale for soluble ACE2 as a potential therapy.
32167747 In a short time following the outbreak, it has been shown that, similar to SARS-CoV, COVID-19 virus exploits the angiotensin-converting enzyme 2 (ACE2) receptor to gain entry inside the cells. […] This finding raises the curiosity of investigating the expression of ACE2 in neurological tissue and determining the possible contribution of neurological tissue damage to the morbidity and mortality caused by COIVD-19. […] Here, we investigate the density of the expression levels of ACE2 in the CNS, the host-virus interaction and relate it to the pathogenesis and complications seen in the recent cases resulting from the COVID-19 outbreak.
32169119 The novel coronavirus uses the same receptor, angiotensin-converting enzyme 2 (ACE2) as that for SARS-CoV, and mainly spreads through the respiratory tract.
32170560 It has been known that, the novel Coronavirus, 2019-nCoV, which is considered similar to SARS-CoV and originated from Wuhan (China), invades human cells via the receptor angiotensin converting enzyme II (ACE2). […] Moreover, lung cells that have ACE2 expression may be the main target cells during 2019-nCoV infection.
32174094 SARS-CoV通过结合血管紧张素转换酶2(ACE2)进入细胞,病变与病程相关,DAD渗出期一般见于病程10~14 d死亡患者。
32186711 Intravenous infusions of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in experimental animals increase the numbers of angiotensin-converting enzyme 2 (ACE2) receptors in the cardiopulmonary circulation. […] ACE2 receptors serve as binding sites for SARS-CoV-2 virions in the lungs.
32187929 According to current observations, 2019-nCoV is weaker than SARS in pathogenesis, but has stronger transmission competence; it’s mechanism of cross-species spread might be related with angiotensin-converting enzyme Ⅱ (ACE2), which is consistent with the receptor SARS-CoV.
32189428 We predict that these individuals are ‘primed’ to be at higher risk because nicotine can directly impact the putative receptor for the virus (ACE2) and lead to deleterious signaling in lung epithelial cells.
32189489 由于2019-nCoV通过棘突糖蛋白与宿主呼吸道上皮细胞的血管紧张素转换酶2(ACE2)结合感染人体,ACE2已被确认为2019-nCoV的受体。 […] 另一方面,ACE2对于多种动脉粥样硬化性心血管疾病(ASCVD)和包括SARS在内的急性肺损伤具有积极的治疗作用。 […] 因此,在2019-nCoV感染背景下的ACE2究竟是人类的敌人还是朋友已成为一个激烈争论的问题。 […] 该文基于ACE2的相关研究成果,对此问题进行深入分析并提出研究展望,希望对2019-nCoV感染的认识和防治有所裨益。.
32197085 Five key amino acid residues involved in the interaction with human ACE2 are completely consistent between Pangolin-CoV and SARS-CoV-2, but four amino acid mutations are present in RaTG13.
32198163 The tissue receptor for COVID-19 is ACE2, and higher levels of ACE2 can protect against ARDS. […] Angiotensin receptor blockers and statins upregulate ACE2.
32199615 Angiotensin I converting enzyme 2 (ACE2), is the host receptor by SARS-CoV-2 to infect human cells. […] Although ACE2 is reported to be expressed in lung, liver, stomach, ileum, kidney and colon, its expressing levels are rather low, especially in the lung. […] SARS-CoV-2 may use co-receptors/auxiliary proteins as ACE2 partner to facilitate the virus entry. […] Consistent with other recent reports, we confirmed that ACE2 was mainly expressed in lung AT2, liver cholangiocyte, colon colonocytes, esophagus keratinocytes, ileum ECs, rectum ECs, stomach epithelial cells, and kidney proximal tubules. […] Intriguingly, we found that the candidate co-receptors, manifesting the most similar expression patterns with ACE2 across 13 human tissues, are all peptidases, including ANPEP, DPP4 and ENPEP.
32199943 Angiotensin converting enzyme 2 (ACE2) is the receptor of SARS-CoV-2, but only ACE2s of certain species can be utilized by SARS-CoV-2. […] Here, we evaluated and ranked the receptor-utilizing capability of ACE2s from various species by phylogenetic clustering and sequence alignment with the currently known ACE2s utilized by SARS-CoV-2. […] As a result, we predicted that SARS-CoV-2 tends to utilize ACE2s of various mammals, except murines, and some birds, such as pigeon.
32201080 ACE2 is the receptor for both SARS-CoV-2 and SARS-CoV. […] To predict the potential host range of SARS-CoV-2, we analyzed the key residues of ACE2 for recognizing S protein. […] The interaction interface between cat/dog/pangolin/Chinese hamster ACE2 and SARS-CoV/SARS-CoV-2 S protein was simulated through homology modeling. […] We identified that N82 in ACE2 showed a closer contact with SARS-CoV-2 S protein than M82 in human ACE2. […] Our finding will provide important insights into the host range of SARS-CoV-2 and a new strategy to design an optimized ACE2 for SARS-CoV-2 infection.
32203189 Here, we identified the receptor-binding domain (RBD) in SARS-CoV-2 S protein and found that the RBD protein bound strongly to human and bat angiotensin-converting enzyme 2 (ACE2) receptors. […] SARS-CoV-2 RBD exhibited significantly higher binding affinity to ACE2 receptor than SARS-CoV RBD and could block the binding and, hence, attachment of SARS-CoV-2 RBD and SARS-CoV RBD to ACE2-expressing cells, thus inhibiting their infection to host cells.
32205090 These manifestations include asymptomatic infection, a hyper-affinity to ACE2 receptors resulting in high transmissibility, false negatives, and an incubation period of up to 22 days.
32208987 Because the ACE2 (angiotensin-converting enzyme 2) protein is the receptor that facilitates coronavirus entry into cells, the notion has been popularized that treatment with renin-angiotensin system blockers might increase the risk of developing a severe and fatal severe acute respiratory syndrome coronavirus-2 infection. […] ACE2 in its full-length form is a membrane-bound enzyme, whereas its shorter (soluble) form circulates in blood at very low levels. […] As a mono-carboxypeptidase, ACE2 contributes to the degradation of several substrates including angiotensins I and II. […] ACE (angiotensin-converting enzyme) inhibitors do not inhibit ACE2 because ACE and ACE2 are different enzymes. […] Although angiotensin II type 1 receptor blockers have been shown to upregulate ACE2 in experimental animals, the evidence is not always consistent and differs among the diverse angiotensin II type 1 receptor blockers and differing organs. […] Moreover, there are no data to support the notion that ACE inhibitor or angiotensin II type 1 receptor blocker administration facilitates coronavirus entry by increasing ACE2 expression in either animals or humans. […] Indeed, animal data support elevated ACE2 expression as conferring potential protective pulmonary and cardiovascular effects.
32210742 The observed changes have significant effect on SARS-CoV-2 spike/ACE2 interaction and produce a reduction in the binding energy, compared to the one of the Bat-CoV to this receptor. […] The data presented in this study suggest a higher affinity of the SARS-Cov-2 spike protein to the human ACE2 receptor, compared to the one of Bat-CoV spike and ACE2.
32213556 Bioinformatics showed sequence mutation of SARS-CoV-2 with m6A methylation and changed binding capacity with ACE2.
32215613 In particular, activity of the angiotensin-converting enzyme 2 (ACE2) is dysregulated in cardiovascular disease, and this enzyme is used by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to initiate the infection. […] Cardiovascular disease and pharmacologic RAS inhibition both increase ACE2 levels, which may increase the virulence of SARS-CoV-2 within the lung and heart. […] Conversely, mechanistic evidence from related coronaviruses suggests that SARS-CoV-2 infection may downregulate ACE2, leading to toxic overaccumulation of Angiotensin II that induces acute respiratory distress syndrome and fulminant myocarditis.
32215622 Molecular docking on the binding between angiotensin-converting enzyme 2 (ACE2) of common laboratory mammals and the receptor-binding domain of the surface spike protein of SARS-CoV-2 suggested that the golden Syrian hamster is an option.
32215956 Studies have identified the SARS-CoV-2 RNA in stool specimens of infected patients, and its viral receptor angiotensin converting enzyme 2 (ACE2) was found to be highly expressed in gastrointestinal epithelial cells.
32219057 Both SARS-CoV and SARS-CoV-2 exhibit a high degree of genetic similarity and bind to the same host cell ACE2 receptor.
32221983 This article reviews the correlation between angiotensin-converting enzyme 2 (ACE2) and severe risk factors for coronavirus disease 2019 (COVID-19) and the possible mechanisms. […] ACE2 is a crucial component of the renin-angiotensin system (RAS). […] The classical RAS ACE-Ang II-AT1R regulatory axis and the ACE2-Ang 1-7-MasR counter-regulatory axis play an essential role in maintaining homeostasis in humans. […] ACE2 is widely distributed in the heart, kidneys, lungs, and testes. […] ACE2 antagonizes the activation of the classical RAS system and protects against organ damage, protecting against hypertension, diabetes, and cardiovascular disease. […] Similar to SARS-CoV, SARS-CoV-2 also uses the ACE2 receptor to invade human alveolar epithelial cells. […] Acute respiratory distress syndrome (ARDS) is a clinical high-mortality disease, and ACE2 has a protective effect on this type of acute lung injury. […] Because of these protective effects of ACE2 on chronic underlying diseases and ARDS, the development of spike protein-based vaccine and drugs enhancing ACE2 activity may become one of the most promising approaches for the treatment of COVID-19 in the future.
32225175 SARS-CoV-2 and SARS-CoV recognize the same receptor - human ACE2 (hACE2)3,4. […] Here we determined the crystal structure of the SARS-CoV-2 receptor-binding domain (RBD) (engineered to facilitate crystallization) in complex with hACE2. […] Compared with the SARS-CoV RBD, a hACE2-binding ridge in SARS-CoV-2 RBD takes a more compact conformation; moreover, several residue changes in SARS-CoV-2 RBD stabilize two virus-binding hotspots at the RBD/hACE2 interface. […] These structural features of SARS-CoV-2 RBD enhance its hACE2-binding affinity. […] Additionally, we show that RaTG13, a bat coronavirus closely related to SARS-CoV-2, also uses hACE2 as its receptor. […] The differences among SARS-CoV-2, SARS-CoV and RaTG13 in hACE2 recognition shed light on potential animal-to-human transmission of SARS-CoV-2.
32225176 To better understand the initial step of infection at an atomic level, we determined the crystal structure of the SARS-CoV-2 spike receptor-binding domain (RBD) bound to the cell receptor ACE2 at 2.45 Å resolution. […] The overall ACE2-binding mode of the SARS-CoV-2 RBD is nearly identical to that of the SARS-CoV RBD, which also utilizes ACE2 as the cell receptor4. […] Structural analysis identified residues in the SARS-CoV-2 RBD that are critical for ACE2 binding, the majority of which either are highly conserved or share similar side chain properties with those in the SARS-CoV RBD. […] Such similarity in structure and sequence strongly argue for convergent evolution between the SARS-CoV-2 and SARS-CoV RBDs for improved binding to ACE2, although SARS-CoV-2 does not cluster within SARS and SARS-related coronaviruses1-3,5.
32227090 Angiotensin-converting enzyme 2 (ACE2), the key host cellular receptor of SARS-CoV-2, has been identified in multiple organs, but its cellular distribution in human heart is not illuminated clearly. […] This study performed the first state-of-art single cell atlas of adult human heart, and revealed that pericytes with high expression of ACE2 might act as the target cardiac cell of SARS-CoV-2. […] And patients with basic heart failure disease showed increased ACE2 expression at both mRNA and protein levels, meaning that if infected by the virus these patients may have higher risk of heart attack and critically ill condition.
32228252 The mechanism for SARS-CoV-2 infection is the requisite binding of the virus to the membrane-bound form of angiotensin-converting enzyme 2 (ACE2) and internalization of the complex by the host cell. […] Recognition that ACE2 is the coreceptor for the coronavirus has prompted new therapeutic approaches to block the enzyme or reduce its expression to prevent the cellular entry and SARS-CoV-2 infection in tissues that express ACE2 including lung, heart, kidney, brain, and gut. […] ACE2, however, is a key enzymatic component of the renin-angiotensin-aldosterone system (RAAS); ACE2 degrades ANG II, a peptide with multiple actions that promote CVD, and generates Ang-(1-7), which antagonizes the effects of ANG II. […] Moreover, experimental evidence suggests that RAAS blockade by ACE inhibitors, ANG II type 1 receptor antagonists, and mineralocorticoid antagonists, as well as statins, enhance ACE2 which, in part, contributes to the benefit of these regimens. […] The current perspective critically examines the evidence for ACE2 regulation by RAAS blockade and statins, the cardiovascular benefits of ACE2, and whether ACE2 blockade is a viable approach to attenuate COVID-19.
32232976 ACE2 is a metalloproteinase and a homolog of carboxypeptidase ACE. […] It hydrolyzes a variety of angiotensin peptides and is the main active peptide of the renin-angiotensin system (RAS).[3] ACE2, which is made of 805 amino acids, is a type I transmembrane glycoprotein with a single extracellular catalytic domain.
32238232 Due to the shared receptor ACE2 and the pathological similarities of the SARS-CoV and 2019-nCoV diseases. […] 分析表明,由于2019-nCoV和SARS冠状病变在人体细胞上有相同的受体(ACE2),因而它们可能有相同的靶器官,如肺、心血管系统和免疫系统。
32238438 Both viruses have evolved an ability to enter host cells through direct interaction with the angiotensin converting enzyme 2 (ACE2) protein at the surface of many cells. […] Here we consider the ability of SARS-CoV2 to enter and infect the human nervous system based on the strong expression of the ACE2 target throughout the brain. […] Moreover, we predict that nicotine exposure through various kinds of smoking (cigarettes, e-cigarettes, or vape) can increase the risk for COVID19 neuroinfection based on known functional interactions between the nicotinic receptor and ACE2.
32239522 Angiotensin-converting enzyme 2 (ACE2) is the receptor for SARS-CoV-2, which determines the potential host range for SARS-CoV-2. […] On the basis of structural information of the complex of human ACE2 and SARS-CoV-2 receptor-binding domain (RBD), we analyzed the affinity to S protein of the 20 key residues in ACE2 from mammal, bird, turtle, and snake. […] Several ACE2 proteins from Primates, Bovidae, Cricetidae, and Cetacea maintained the majority of key residues in ACE2 for associating with SARS-CoV-2 RBD. […] The simulated structures indicated that ACE2 proteins from Bovidae and Cricetidae were able to associate with SARS-CoV-2 RBD. […] The simulated structures showed several key contacts with SARS-CoV-2 RBD in turtle and snake ACE2 were abolished.
32244779 We detected, amongst others, affected apoptotic and mitochondrial mechanisms, and a downregulation of the ACE2 protein receptor, notions that can be used to develop specific therapies against this new virus.
32244852 Smoking can upregulate angiotensin-converting enzyme-2 (ACE2) receptor, the known receptor for both the severe acute respiratory syndrome (SARS)-coronavirus (SARS-CoV) and the human respiratory coronavirus NL638. […] ACE2 could be a novel adhesion molecule for SARS-CoV-2 causing Covid-19 and a potential therapeutic target for the prevention of fatal microbial infections, and therefore it should be fast tracked and prioritized for research and investigation.
32246845 SARS-CoV-2 was reported to enter cells via binding to ACE2, followed by its priming by TMPRSS2. […] Here, we investigate ACE2 and TMPRSS2 expression levels and their distribution across cell types in lung tissue (twelve donors, 39,778 cells) and in cells derived from subsegmental bronchial branches (four donors, 17,521 cells) by single nuclei and single cell RNA sequencing, respectively. […] While TMPRSS2 is expressed in both tissues, in the subsegmental bronchial branches ACE2 is predominantly expressed in a transient secretory cell type.
32249956 Human ACE2 is now established as a receptor for the SARS-CoV-2 spike protein. […] Where variations in the viral spike protein, in turn, lead to the cross-species transmission of the virus, genetic variations in the host receptor ACE2 may also contribute to the susceptibility and/or resistance against the viral infection. […] This study aims to explore the binding of the proteins encoded by different human ACE2 allelic variants with SARS-CoV-2 spike protein. […] Briefly, coding variants of ACE2 corresponding to the reported binding sites for its attachment with coronavirus spike protein were selected and molecular models of these variants were constructed by homology modeling. […] The models were then superimposed over the native ACE2 and ACE2-spike protein complex, to observe structural changes in the ACE2 variants and their intermolecular interactions with SARS-CoV-2 spike protein, respectively. […] Despite strong overall structural similarities, the spatial orientation of the key interacting residues varies in the ACE2 variants compared with the wild-type molecule. […] Most ACE2 variants showed a similar binding affinity for SARS-CoV-2 spike protein as observed in the complex structure of wild-type ACE2 and SARS-CoV-2 spike protein. […] However, ACE2 alleles, rs73635825 (S19P) and rs143936283 (E329G) showed noticeable variations in their intermolecular interactions with the viral spike protein. […] In summary, our data provide a structural basis of potential resistance against SARS-CoV-2 infection driven by ACE2 allelic variants.
32255491 Angiotensin converting enzyme 2 (ACE2) is the major enzyme responsible for conversion of Ang II into Ang-(1-7). […] In recognition of the importance of ACE2 and to celebrate 20 years since its discovery, the journal will publish a focused issue on the basic science and (patho)physiological role of this multifunctional protein.
32257537 Furthermore, the gene expression profile showed MSCs were ACE2- and TMPRSS2- which indicated MSCs are free from COVID-19 infection.
32264791 Angiotensin-converting enzyme (ACE2) has a multiplicity of physiological roles that revolve around its trivalent function: a negative regulator of the renin-angiotensin system (RAS), facilitator of amino acid transport, and the SARS-CoV and SARS-CoV-2 receptor. […] ACE2 is widely expressed, including, in the lungs, cardiovascular system, gut, kidneys, central nervous system, and adipose tissue. […] ACE2 has recently been identified as the SARS-CoV-2 receptor, the infective agent responsible for COVID-19, providing a critical link between immunity, inflammation, ACE2, and cardiovascular disease. […] Although sharing a close evolutionary relationship with SARS-CoV, the receptor-binding domain of SARS-CoV-2 differs in several key amino acid residues, allowing for stronger binding affinity with the human ACE2 receptor, which may account for the greater pathogenicity of SARS-CoV-2. […] The loss of ACE2 function following binding by SARS-CoV-2 is driven by endocytosis and activation of proteolytic cleavage and processing. […] The ACE2 system is a critical protective pathway against heart failure with reduced and preserved ejection fraction including, myocardial infarction and hypertension, and against lung disease and diabetes. […] The control of gut dysbiosis and vascular permeability by ACE2 has emerged as an essential mechanism of pulmonary hypertension and diabetic cardiovascular complications. […] Recombinant ACE2, gene-delivery of Ace2, Ang 1-7 analogs, and Mas receptor agonists enhance ACE2 action and serve as potential therapies for disease conditions associated with an activated RAS. […] Recombinant human ACE2 has completed clinical trials and efficiently lowered or increased plasma angiotensin II and angiotensin 1-7 levels, respectively. […] Our review summarizes the progress over the past 20 years, highlighting the critical role of ACE2 as the novel SARS-CoV-2 receptor and as the negative regulator of the RAS, together with implications for the COVID-19 pandemic and associated cardiovascular diseases.
32266994 The authors mentioned that angiotensin-converting enzyme 2 (ACE2) is protective against novel coronavirus disease 2019 (COVID-19). […] We would like to explain how cytosolic pH increases the COVID-19 infection by affecting the ACE2.
32267499 Angiotensin-converting enzyme 2 (ACE2) has emerged as a key regulator of the renin-angiotensin system in cardiovascular (CV) disease and plays a pivotal role in infections by coronaviruses and influenza viruses. […] The present review is primarily focused on the findings to indicate the role of ACE2 in the relationship of coronaviruses and influenza viruses to CV disease. […] It is postulated that the risk of coronavirus or influenza virus infection is high, at least partly due to high ACE2 expression in populations with a high CV risk.
32268515 Previous studies reported that Angiotensin converting enzyme 2 (ACE2) is the main cell receptor of SARS-CoV and SARS-CoV-2. […] In the present study we investigated in silico the basic mechanism of ACE2 in the lung and provided evidences for new potentially effective drugs for Covid-19. […] Specifically, we used the gene expression profiles from public datasets including The Cancer Genome Atlas, Gene Expression Omnibus and Genotype-Tissue Expression, Gene Ontology and pathway enrichment analysis to investigate the main functions of ACE2-correlated genes. […] We constructed a protein-protein interaction network containing the genes co-expressed with ACE2. […] Our results demonstrate that the genes correlated with ACE2 are mainly enriched in the sterol biosynthetic process, Aryldialkylphosphatase activity, adenosylhomocysteinase activity, trialkylsulfonium hydrolase activity, acetate-CoA and CoA ligase activity.
32270559 Cardiac manifestations etiology seems to be multifactorial, comprising direct viral myocardial damage, hypoxia, hypotension, enhanced inflammatory status, ACE2-receptors downregulation, drug toxicity, endogenous catecholamine adrenergic status, among others.
32273490 It remains unclear why children and young adults are less severely affected than older individuals, but this might involve differences in immune system function in the elderly and/or differences in the expression/function of the cellular receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) - Angiotensin converting enzyme 2 (ACE2).
32275082 The conjunctival mucosa is directly exposed to infectious droplets expelled by patients during close contact and fomites when the eye is touched by contaminated hands.2, 3 More over, the mucosa of the conjunctiva and upper respiratory tract is connected by nasolacrimal duct, and share the same entry receptor of SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2), on host cell membranes.2, 3 Hence, it is reasonable to postulate that the conjunctiva may be easily involved in SARS-CoV-2 infection, and may even act as a route of transmission during SARS-CoV-2 infection.
32275855 Recently, ACE2 was reported as an entry receptor for SARS-CoV-2. […] In this study, we present the crystal structure of the C-terminal domain of SARS-CoV-2 (SARS-CoV-2-CTD) spike (S) protein in complex with human ACE2 (hACE2), which reveals a hACE2-binding mode similar overall to that observed for SARS-CoV.
32276140 Specially, we provide evidence in lupus to suggest hypomethylation and overexpression of ACE2, which is located on the X chromosome and encodes a functional receptor for the SARS-CoV-2 spike glycoprotein. […] Oxidative stress induced by viral infections exacerbates the DNA methylation defect in lupus, possibly resulting in further ACE2 hypomethylation and enhanced viremia. […] Epigenetic control of the ACE2 gene might be a target for prevention and therapy in COVID-19.
32277367 Angiotensin converting enzyme 2 (ACE2) appears important for viral entry into pneumocytes; dysbalance in ACE2 as caused by ACE inhibitors or ibuprofen may predispose to severe disease.
32278065 SARS-CoV uses the the angiotensin-converting enzyme 2 (ACE2) and the serine protease TMPRSS2 for S protein priming. […] ACE2 and TMPRSS2 are not only expressed in lung, but also in the small intestinal epithelia. […] ACE2 is expressed furthermore in the upper esophagus, liver, and colon. […] SARS-CoV-2 binding affinity to ACE2 is significantly higher (10-20 times) compared with SARS-CoV.
32279908 This observation has been related to the use of drugs that can increase the cellular expression of angiotensin-converting enzyme 2 (ACE2) that has been recognized as target to which the virus bind to cells.
32281327 The results showed that the research team screened out 46 active ingredients from candidate TCMs that could act on the novel coronavirus S-protein-binding site of human ACE2 protein, which were mainly attributed to 7 herbs such as Lonicerae Japonicae Flos and Mori Folium.
32281328 By combining the diagnosis and treatment scheme of Hunan province’s and angiotensin converting enzyme 2(ACE2) inhibitors screening from literature, present study also discussed the rational application of candidate herbs to this epidemic situation. […] Trichosanthis Fructus obtained by PLP inhibitors screening and Fritillaria verticillata obtained by ACE2 inhibitors screening were parts of the Sangbei Zhisou Powder and Xiaoxianxiong Decoction, which might be applicable to the syndromes of cough and dyspnea. […] Mori Folium, Lonicerae Japonicae Flos and Forsythiae Fructus obtained by ACE2 inhibitors screening were included in the Sangju Decoction and Yinqiaosan, which might be applicable to the syndromes of warm pathogen attacking lung and cough and dyspnea.
32283006 Multiple non-neuronal cell types present in the olfactory epithelium express two host receptors, ACE2 and TMPRSS2 proteases, that facilitate SARS-CoV-2 binding, replication, and accumulation.
32283711 SARS-CoV-2 shares both high sequence similarity and the use of the same cell entry receptor, angiotensin-converting enzyme 2 (ACE2), with severe acute respiratory syndrome coronavirus (SARS-CoV). […] Here, we investigate the expression pattern of ACE2 in adult human testes at the level of single-cell transcriptomes. […] The results indicate that ACE2 is predominantly enriched in spermatogonia and Leydig and Sertoli cells. […] Gene Set Enrichment Analysis (GSEA) indicates that Gene Ontology (GO) categories associated with viral reproduction and transmission are highly enriched in ACE2-positive spermatogonia, while male gamete generation related terms are downregulated. […] Cell-cell junction and immunity-related GO terms are increased in ACE2-positive Leydig and Sertoli cells, but mitochondria and reproduction-related GO terms are decreased.
32285293 Both COVID-19 and SARS-CoV belong to the coronavirus family and both invade target cells through ACE2. […] An in-depth understanding of ACE2 and a series of physiological and physiological changes caused by the virus invading the human body may help to discover and explain the corresponding clinical phenomena and then deal with them timely. […] In addition, ACE2 is a potential therapeutic target. […] This article will summarize the role of ACE2 in multiple organ damage caused by COVID-19 and SARS-CoV, targeted blocking drugs against ACE2, and drugs that inhibit inflammation in order to provide the basis for subsequent related research, diagnosis and treatment, and drug development.
32285974 SARS-CoV-2 was reported to enter cells via binding to ACE2, followed by its priming by TMPRSS2. […] Here, we investigate ACE2 and TMPRSS2 expression levels and their distribution across cell types in lung tissue (twelve donors, 39,778 cells) and in cells derived from subsegmental bronchial branches (four donors, 17,521 cells) by single nuclei and single cell RNA sequencing, respectively. […] While TMPRSS2 is strongly expressed in both tissues, in the subsegmental bronchial branches ACE2 is predominantly expressed in a transient secretory cell type.
32286790 The inhibitors are mostly formed by two sequential self-supporting α-helices (bundle) extracted from the protease domain (PD) of angiotensin-converting enzyme 2 (ACE2), which bind to the SARS-CoV-2 receptor binding domains.
32290077 Previous studies showed that SARS-CoV-2 is highly homologous to SARS-CoV and infects humans through the binding of the spike protein to ACE2. […] It was found that SARS-CoV-2 binds ACE2 with a higher affinity than SARS-CoV, which may partly explain that SARS-CoV-2 is much more infectious than SARS-CoV. […] Our computation also suggested that the RBD-ACE2 binding for SARS-CoV-2 is much more temperature-sensitive than that for SARS-CoV.
32291076 SARS-CoV-2 enters into and infects host cells through its spike glycoprotein recognizing the cell receptor Angiotensin-converting enzyme II (ACE2). […] Here, we noticed that ACE2 was further enhanced by SARS-CoV-2 infection. […] Human germ cells and early embryos express high level of ACE2. […] Notably, RNA-seq result showed that reduction of H3K27me3, but not H3K4/9/36me3, led to upregulation of Ace2 expression in mouse germ cell line GC-2. […] In agreement with this result, we found in human embryonic stem cells that ACE2 expression was significantly increased in absence of EZH2, the major enzyme catalyzing H3K27me3. […] ChIP-seq analysis further confirmed decrease of H3K27me3 signal and increase of H3K27ac signal at ACE2 promoter upon EZH2 knockout. […] Therefore, we propose that EZH2-mediated H3K27me3 at ACE2 promoter region inhibits ACE2 expression in mammalian cells. […] Our discovery provides clues for pathogenesis and targeted drug therapy towards ACE2 expression for prevention and adjuvant therapy of COVID-19.
32291526 Worse outcomes appear to be more prevalent in patients with hypertension and diabetes mellitus (DM), possibly due to overexpression of angiotensin-converting enzyme 2 (ACE2) receptor in airway alveolar epithelial cells. […] Investigators suspect that SARS-CoV-2 uses the ACE2 receptor to enter the lungs in a mechanism similar to SARS-CoV. […] Positive effects include ACE2 receptor blockade, disabling viral entry into the heart and lungs, and an overall decrease in inflammation secondary to ACEI/ARB. […] Negative effects include a possible retrograde feedback mechanism, by which ACE2 receptors are upregulated.
32292884 The SARS-CoV-2 virus uses the ACE2 receptor as the entry point to the host cells. […] ARBs/ACEIs which are widely used in elderly patients, have been found to be associated with overexpression of ACE2. […] To decrease the severity of COVID-19 infection, ARB/ACEI should be switched to another class drug not known to cause a rise in ACE2 until the COVID-19 infection subsides.
32293003 This is related to the role of angiotensin-converting enzyme 2 (ACE2) for SARS-CoV-2 entry into cells, and expression of ACE2 in the lung, cardiovascular system, kidney, and other tissues.
32293710 COVID-19 infection and its severity can be explained by the concentration of glycosylated SARS- CoV-2 viral particles in the lung epithelium, the concentration of glycosylated angiotensin converting enzyme receptor 2 (ACE2) in the lung epithelium, and the degree and control of the pulmonary immune response to the SARS-CoV-2 spike protein at approximately day 8-10 after symptom onset, which may be related to both. […] Binding of ACE2 by SARS-CoV-2 in COVID-19 also suggests that prolonged uncontrolled hyperglycemia, and not just a history of diabetes mellitus, may be important in the pathogenesis of the disease.
32293910 The virus uses the ACE2 receptor for internalization, aided by TMPRSS2 protease. […] Virus-induced ACE2 down regulation may attenuate its function, diminish its anti-inflammatory role, and heightened angiotensin II effects in the predisposed patients.
32294179 Two coronavirus receptor proteins, Angiotensin Converting Enzyme 2 (ACE2) and Dipeptidyl Peptidase-4 (DPP4) are also established transducers of metabolic signals and pathways regulating inflammation, renal and cardiovascular physiology, and glucose homeostasis. […] Here we review the basic and clinical science spanning the intersections of diabetes, coronavirus infections, ACE2, and DPP4 biology, highlighting clinical relevance and evolving areas of uncertainty underlying the pathophysiology and treatment of T2D in the context of coronavirus infection.
32298273 Angiotensin-converting enzyme 2 (ACE2) is now confirmed as the receptor of SARS-CoV-2 and plays essential roles in human infection and transmission. […] In present study, we collected the online available single-cell RNA sequencing (scRNA-seq) data to evaluate the cell specific expression of ACE2 in maternal-fetal interface as well as in multiple fetal organs. […] Our results revealed that ACE2 was highly expressed in maternal-fetal interface cells including stromal cells and perivascular cells of decidua, and cytotrophoblast and syncytiotrophoblast in placenta. […] Meanwhile, ACE2 was also expressed in specific cell types of human fetal heart, liver and lung, but not in kidney. […] And in a study containing series fetal and post-natal mouse lung, we observed ACE2 was dynamically changed over the time, and ACE2 was extremely high in neonatal mice at post-natal day 1~3.
32300101 Besides lungs, salivary glands and tongue are possibly another hosts of 2019-nCoV due to expression of ACE2.
32301766 Severe acute respiratory syndrome coronavirus-2019 (SARS-CoV-2), the causative virus of COVID-19, infects host cells through angiotensin converting enzyme 2 (ACE2). […] Pre-clinical models suggest that ACE2 upregulation confers protective effects in acute lung injury. […] Additionally, renin-angiotensin aldosterone system inhibitors reduce adverse atherosclerotic cardiovascular disease, heart failure and chronic kidney disease outcomes, but may increase ACE2 levels. […] We review current knowledge of the role of ACE2 in cardiovascular physiology and SARS-CoV-2 virology as well as clinical data to inform the management of patients with or at risk for COVID-19 who require renin-angiotensin-aldosterone system inhibitor therapy.
32302706 Angiotensin-converting enzyme 2 (ACE2) maintains the homeostasis of RAS as a negative regulator. […] Recently, ACE2 was identified as the receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the coronavirus that is causing the pandemic of Coronavirus disease 2019 (COVID-19). […] Since SARS-CoV-2 must bind with ACE2 before entering the host cells in humans, the distribution and expression of ACE2 may be critical for the target organ of the SARS-CoV-2 infection. […] Moreover, accumulating evidence has demonstrated the implication of ACE2 in the pathological progression in tissue injury and several chronic diseases, ACE2 may also be essential in the progression and clinical outcomes of COVID-19. […] Therefore, we summarized the expression and activity of ACE2 in various physiological and pathological conditions, and discussed its potential implication in the susceptibility of SARS-CoV-2 infection and the progression and prognosis of COVID-19 patients in the current review.
32303424 It has been reported that SARS-CoV-2 may use ACE2 as a receptor to gain entry into human cells, in a way similar to that of SARS-CoV. […] Analyzing the distribution and expression level of ACE2 may therefore help reveal underlying mechanisms of viral susceptibility and post-infection modulation. […] In this study, we utilized previously uploaded information on ACE2 expression in various conditions including SARS-CoA to evaluate the role of ACE2 in SARS-CoV and extrapolate that to COVID-19. […] We found that the expression of ACE2 in healthy populations and patients with underlying diseases was not significantly different. […] However, based on the elevated expression of ACE2 in cigarette smokers, we speculate that long-term smoking may be a risk factor for COVID-19. […] Analysis of ACE2 in SARS-CoV infected cells suggests that ACE2 is not only a receptor but is also involved in post-infection regulation, including immune response, cytokine secretion, and viral genome replication.
32303609 For instance, it is an important question to understand whether patients with IBD (eg, due to intestinal ACE2 expression) might be particularly susceptible to covid-19 and the cytokine release syndrome associated with lung injury and fatal outcomes.
32304747 The protective effect of ACE2 is enhanced by ARB administration.
32305401 SARS-CoV2 host cell infection is mediated by the binding to angiotensin-converting enzyme 2 (ACE2). […] Systemic dysregulation observed in SARS-CoV was previously postulated to be due to ACE2/Ang1-7/Mas axis downregulation, increased ACE2 activity was shown to mediate disease protection. […] Since angiotensin II receptor blockers (ARBs), ACE inhibitors, and mineralocorticoid receptor antagonists (MRAs) increase ACE2 receptor expression, it has been tacitly believed that the use of these agents may facilitate viral disease, thus they should not be used in high-risk patients with cardiovascular disease. […] Based on the anti-inflammatory benefits of the upregulation of the ACE2/Ang1-7/Mas axis and previously demonstrated benefits of lung function improvement in SARS-CoV infections, we hypothesize that the benefits of treatment with renin-angiotensin system inhibitors in SARS-COV2 may outweigh the risks and at the very least should not be withheld.
32305506 Angiotensin converting enzyme 2 (ACE2), a component of the renin-angiotensin system, whose expression dominates on lung alveolar epithelial cells, is the human cell receptor of SARS-CoV-2, the causative agent of COVID-19. […] We decided to use the analogy of a play and speculate about the possible impact in this tragedy of 1) air pollution via the interference of nitrogen dioxide on ACE2 expression; 2) the dual role of nicotine; 3) the hypothetical involvement of ACE2 polymorphisms, the relationships of which with ethnic factors and susceptibility to cardiovascular disease seems intriguing; 4) the impact on the severity of infection of hypertension and related medications acting on the renin/angiotensin system, and, finally, 5) the possible helpful role of chloroquine, thanks to its capacity of modifying ACE2 affinity to the viral spike protein by altering glycosylation.
32306452 Human angiotensin-converting enzyme 2 (ACE2) facilitates cellular entry of severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2 as their common receptor. […] During infection, ACE2-expressing tissues become direct targets, resulting in serious pathological changes and progressive multiple organ failure or even death in severe cases. […] However, as an essential component of renin-angiotensin system (RAS), ACE2 confers protective effects in physiological circumstance, including maintaining cardiovascular homeostasis, fluid, and electrolyte balance. […] The absence of protective role of ACE2 leads to dysregulated RAS and thus acute changes under multiple pathological scenarios including SARS. […] We reasonably speculate several potential directions of clinical management including host-directed therapies aiming to restore dysregulated RAS caused by ACE2 deficiency. […] Enriched knowledge of ACE2 learned from SARS and COVID-19 outbreaks can provide, despite their inherent tragedy, informative clues for emerging pandemic preparedness.
32307653 This process, and the possible direct viral invasion of progenitor/stem cells via CD147 or ACE2, could result in the decline of these cellular stocks and failing lung repair.
32307955 COVID-19 enters the human cell using the ACE2, an enzyme abundant in renal tubular epithelial cells. […] Moreover, medications based on RAAS inhibition, such and ACE inhibitors and ARBs, upregulate the enzyme ACE2 and could therefore hypothetically explain the high prevalence of hypertension and diabetes reported as previous diagnoses in severe cases.
32310688 The angiotensin converting enzyme-2 (ACE2) cellular receptor is responsible for the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), thus impacting the entrance and clearance of the virus. […] Studies demonstrate that upregulation of ACE2 has a protective effect on SARS-CoV-2 illness severity. […] Moreover, animal studies demonstrate that dietary intake can modulate ACE2 gene expression and function. […] A high intake of resveratrol may have a protective role, upregulating ACE2, whereas a high intake of dietary fat may have a detrimental role, downregulating ACE2. […] As such, we postulate on the biological plausibility of interactions between dietary fat and/or resveratrol and ACE2 gene variations in the modulation of SARS-CoV-2 illness severity.
32310915 ACE-inhibitors and ARBs may increase the expression of ACE2 receptors, which are the sites of viral entry into the human organism. […] ACE2 receptors are ubiquitous, although they are extremely abundant on the cell surface of type 2 pneumocytes. […] The increased expression of ACE2 for effect of ACE-inhibitors and ARBs can be detected by increased production of angiotensin1-7 and mRNA related to ACE2. […] There is the fear that the increased expression of ACE2 induced by ACE-inhibitors and ARBs may ultimately facilitate the entry and diffusion of the SARS-CoV-2 virus. […] Indeed, studies conducted in different laboratories demonstrated that ACE2 receptors show a down-regulation (i.e. the opposite of what would happen with ACE-inhibitors and ARBs) for effect of their interaction with the virus. […] In animal studies, down-regulation of ACE2 has been found as prevalent in the pulmonary areas infected by virus, but not in the surrounding areas. […] In these studies, virus-induced ACE2 down-regulation would lead to a reduced formation of angiotensin1-7 (because ACE2 degrades angiotensin II into angiotensin1-7) with consequent accumulation of angiotensin II.
32311451 ACE2, as the major known functional receptor of the 2019 novel coronavirus (2019-nCoV) attracted our attention. […] Furthermore, we used online datasets to analyze ACE2 expression in different human organs, especially in the small intestine, to explore the relationship between ACE2 expression patterns and clinical symptoms. […] The results reveal that ACE2 mRNA and protein are highly expressed in the small intestinal enterocytes but not in the goblet cells or intestinal immune cells. […] High expression of ACE2 on the surface cells in the digestive tract may lead to gastrointestinal symptoms and inflammation susceptibility. […] ACE2 expression on surface cells of the small intestine may mediate the invasion and amplification of the virus and activation of gastrointestinal inflammation.
32311651 The virus attaches to the ACE2 enzyme at low cytosolic pH values and enters into the cell and causes infection. […] Especially in the presence of diabetes mellitus and accompanying comorbid conditions such as hypertension, obesity, old age, and smoking, cytosolic pH is low, thus the virus easily may enter the cell by attaching to ACE2. […] ACEIs and ARBs lead to a reduction in angiotensin II level by increasing the ACE2 level, thus they cause a low cytosolic pH. […] Increased cardiac ACE2 levels due to ACEIs and ARBs can trigger cardiac arrhythmias and myocarditis by causing the virus to easily enter the heart tissue. […] There is ACE2 activity in the rostral ventrolateral medulla in the brain stem.
32313363 Although sequence data indicate that Chiroptera are a good candidate for the original reservoir of SARS-CoV, the structural biology of the spike protein of SARS-CoV isolated from Chiroptera suggests that these viruses are not able to interact with the human variant of the receptor of SARS-CoV, angiotensin-converting enzyme 2 (ACE2).
32314329 The new SARS-CoV-2 virus enters cells via angiotensin-converting enzyme 2 (ACE2). […] ACE2 counteracts ACE and angiotensin II in the renin-angiotensin-aldosterone system (RAAS) and has critical functions in the lung and cardiovascular system. […] SARS-CoV was found to down-regulate ACE2, leaving angiotensin II unbalanced in affected organs.
32316118 In this sense, molecular and genetic variations associated with malaria (e.g., in ACE2) might play a protective role against coronavirus infection.
32316719 Objective: Angiotensin converting enzyme 2 (ACE2) and Transmembrane serine protease 2 (TMPRSS2) are the key proteins for 2019-nCoV entry into host cells. […] To evaluate the potential infection risk of 2019-nCoV on ocular surface, we compared ACE2 and TMPRSS2 expression among different eye tissues. Methods: Experimental article. […] Real-time PCR was performed to quantify ACE2 and TMPRSS2 gene expression in conjunctiva, cornea, lacrimal gland, iris, lens, retina, lung, heart, kidney, and liver from male mice. […] Published transcriptome datasets were extracted to generate the expression comparasion of ACE2 and TMPRSS2 between human conjunctival and corneal tissues, and results were analyzed with Mann-Whitney U test. […] Female mice, aging mice, STZ-induced diabetic mice, diabetic group control mice were also subjected to ACE2 expression analysis. […] Results were analyzed using Student’s t-test. Results: The expression of ACE2 and TMPRSS2 genes were the highest in conjunctiva among all the six mice eye tissues explored. […] ACE2 and TMPRSS2 shared similar expression pattern with the staining concentrated in corneal epithelium, conjunctival epithelium and lacrimal gland serous cells. […] The expression levels of ACE2 showed sex-difference. […] Female mice had lower ACE2 in conjunctiva and cornea than male mice, with the expression levels taking only 43% (t=3.269, P=0.031) and 63% (t=4.080, P=0.015) of that in the male conjunctiva and cornea, respectively. […] Diabetic mice expressed more ACE2 in conjunctiva (1.21-fold, P>0.05) and lacrimal gland (1.10-fold, P>0.05) compared with the control group. […] No significant difference on ACE2 expression was found between the aging and young adult mice. […] The expression level of human conjunctiva ACE2 and TMPRSS2 were significantly higher than that in the cornea (P=0.007), with 5.74-fold and 12.84-fold higher in the conjunctiva than in the corneal epithelium cells, which resembled the situation in mice. Conclusion: The observation of high-level ACE2 and TMPRSS2 expression in conjunctiva among the 6 eye tissues examined suggests that conjunctiva serves as an infection target tissue of 2019-nCoV. (Chin J Ophthalmol, 2020, 56:). 目的: 分析眼部组织新型冠状病毒侵染和激活关键蛋白人血管紧张素转换酶2(ACE2)和跨膜丝氨酸蛋白酶2(TMPRSS2)的表达情况,探讨新型冠状病毒在眼部的侵染基础。 […] 使用荧光定量PCR分析小鼠结膜、角膜、泪腺、虹膜、晶状体、视网膜ACE2基因和TMPRSS2基因表达情况,并与肺脏、心脏、肾脏、肝脏中两个基因的表达量进行比较。 […] 使用免疫组化染色分析了小鼠各组织中ACE2和TMPRSS2蛋白的分布和表达情况。 […] 另取山东省眼科研究所红十字眼库接收的符合捐献条件的志愿者角膜及结膜组织切片,与小鼠眼部ACE2蛋白和TMPRSS2蛋白表达进行验证比较。 […] 同时通过分析已发表的人眼部组织转录组数据库,比较人角膜和结膜中ACE2和TMPRSS2基因的表达情况。 […] 对不同性别、年龄、及糖尿病条件下小鼠眼表组织的ACE2基因表达变化进行分析,采用独立样本t检验对数据进行统计学分析。 […] 结果: 在小鼠6种眼部组织中,结膜ACE2基因和TMPRSS2基因表达量最高,但均低于肾脏和肺脏;ACE2和TMPRSS2蛋白阳性染色集中于结膜上皮、角膜上皮和泪腺腺泡。 […] ACE2基因的表达具有性别的区别,在雌性小鼠结膜和角膜的表达显著低于雄性小鼠,分别为雄性相应组织的43% (t=3.269,P=0.031)和63% (t=4.080,P=0.015);糖尿病小鼠结膜和泪腺中的ACE2基因表达略高于非糖尿病小鼠,分别为1.21倍和1.10倍 (P>0.05);在年龄上ACE2基因表达的差异无统计学意义。 […] 与小鼠相似,人结膜ACE2和TMPRSS2基因表达量显著高于角膜(P=0.007),分别约为角膜上皮基因表达量的5.74倍和12.84倍。 […] 结论: 结膜中ACE2基因和TMPRSS2的表达在6种检测的眼部组织中最高,提示结膜是新型冠状病毒眼部感染的主要靶组织。
32317203 The virus binds and enters through angiotensin-converting enzyme 2 (ACE2).
32318865 While limited data exist, potential mechanisms of cardiac injury include direct viral entry through the angiotensin-converting enzyme 2 (ACE2) receptor and toxicity in host cells, hypoxia-related myocyte injury, and immune-mediated cytokine release syndrome.
32320478 Concerns have been raised regarding the safety of angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in patients with coronavirus disease of 2019 (COVID-19), based on the hypothesis that such medications may raise expression of ACE2, the receptor for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). […] We conducted a literature review of studies (n = 12) in experimental animals and human subjects (n = 12) and evaluated the evidence regarding the impact of administration of ACEIs and ARBs on ACE2 expression. […] We prioritized studies that assessed ACE2 protein expression data, measured directly or inferred from ACE2 activity assays. […] The findings in animals are inconsistent with respect to an increase in ACE2 expression in response to treatment with ACEIs or ARBs. […] Those studies that report increases in ACE2 expression tend to involve acute injury models and/or higher doses of ACEIs or ARBs than are typically administered to patients. […] Data from human studies overwhelmingly imply that administration of ACEIs/ARBs does not increase ACE2 expression. […] Available evidence, in particular, data from human studies, does not support the hypothesis that ACEI/ARB use increases ACE2 expression and the risk of complications from COVID-19.
32323279 Twenty years ago, an enzyme homologous to the previously known angiotensin-converting enzyme (ACE) was identified, and subsequently named ACE2. […] In the renin-angiotensin system (RAS), ACE2 has counter-regulatory functions against the classical effector peptide angiotensin II, for example in blood pressure regulation and cardiovascular remodeling. […] However, ACE2 provides an initially unexpected interesting link between virology and cardiovascular medicine. […] That is, ACE2 represents the binding receptor for the cellular uptake of SARS-CoV and SARS-CoV-2 viruses. […] Thus, ACE2 is relevant for COVID-19. […] In this context, it was suspected that therapy with RAS blockers might promote transmission and complications of COVID-19 by upregulation of ACE2 expression. […] The aim of this short review is, to describe the link between the RAS, particularly ACE2, and COVID-19.
32323565 Colocalization of angiotensin-converting enzyme 2 (ACE2) and TMPRSS2 enables severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) to enter the cells.
32325025 (Cell) identify ACE2 as a SARS-CoV-2 receptor, and the latter show its entry mechanism depends on cellular serine protease TMPRSS2.
32326602 Finally, determining the structural-functional relationships of the S protein of SARS-CoV-2 will provide new insights into inhibition of interactions between S protein and angiotensin-converting enzyme 2 (ACE2) and enable us to develop novel therapeutic approaches for novel coronavirus SARS-CoV-2.
32327202 Furthermore, the receptor of SARS-CoV-2, ACE2 was found to be upregulated in patients with COVID-19, and immunostaining with SARS-CoV nucleoprotein antibody was positive in tubules.
32330302 I would like to talk about the role of ACE2 in endothelial cell function.
32331255 The interaction of the SARS-CoV-2 spike protein with the human ACE2 (angiotensin-converting enzyme 2) receptor, and its subsequent cleavage by serine protease and fusion, are the main events in the pathophysiology. […] The serine protease inhibitors, spike protein-based vaccines, or ACE2 blockers may have therapeutic potential in the near future.
32331343 An enzymatic system involved in this different predisposition could be represented by angiotensin converting enzyme 2 (ACE2). […] ACE2 is activated and down-regulated by the spike protein of the virus and allows the penetration of SARS-CoV-2 into epithelial cells and myocardium. […] Data on the experimental animal have shown that 17ß-estradiol increases the expression and activity of ACE2 in both adipose tissue and kidney. […] Spontaneously hypertensive male mice have a higher myocardial ACE2 expression than females and its levels decrease after orchiectomy. […] Evidence that sex hormones are able to modulate the expression of ACE2 could help in interpreting epidemiological results and in designing more appropriate intervention strategies.
32332765 SARS-CoV-2 has been shown to use the same cell entry receptor as SARS-CoV, angiotensin-converting enzyme 2 (ACE2). […] In this report, we generate a recombinant protein by connecting the extracellular domain of human ACE2 to the Fc region of the human immunoglobulin IgG1. […] A fusion protein containing an ACE2 mutant with low catalytic activity is also used in this study.
32333222 Phylogenetic analysis of full-length genome sequences obtained from infected patients showed that SARS-CoV-2 is similar to severe acute respiratory syndrome coronavirus (SARS-CoV) and uses the same cell entry receptor, angiotensin-converting enzyme 2 (ACE2), as SARS-CoV.
32333398 We propose that an imbalance in the action of ACE1- and ACE2-derived peptides, thereby enhancing angiotensin II (Ang II) signalling is primary driver of COVID-19 pathobiology. […] ACE1/ACE2 imbalance occurs due to the binding of SARS-CoV-2 to ACE2, reducing ACE2-mediated conversion of Ang II to Ang peptides that counteract pathophysiological effects of ACE1-generated ANG II. […] This hypothesis suggests several approaches to treat COVID-19 by restoring ACE1/ACE2 balance: (a) AT receptor antagonists; (b) ACE1 inhibitors (ACEIs); (iii) agonists of receptors activated by ACE2-derived peptides (e.g. […] Ang (1-7), which activates MAS1); (d) recombinant human ACE2 or ACE2 peptides as decoys for the virus. […] Reducing ACE1/ACE2 imbalance is predicted to blunt COVID-19-associated morbidity and mortality, especially in vulnerable patients.
32333601 We hypothesized that the viral entry molecules angiotensin I converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) are expressed in the intestine. […] We examined the expression of Ace2 and Tmprss2 by quantitative polymerase chain reacion in animal models of IBD. […] Publicly available data from organoids and mucosal biopsies from patients with IBD were examined for expression of ACE2 and TMPRSS2. […] ACE2 and TMPRSS2 were abundantly expressed in the ileum and colon and had high expression in intestinal epithelial cells. […] In animal models, inflammation led to downregulation of epithelial Ace2. […] Expression of ACE2 and TMPRSS2 was not increased in samples from patients with compared with those of control patients. […] In CD11b-enriched cells but not T-cells, the level of expression of ACE2 and TMPRSS2 in the mucosa was comparable to other functional mucosal genes and was not affected by inflammation. […] Anti-tumor necrosis factor drugs, vedolizumab, ustekinumab, and steroids were linked to significantly lower expression of ACE2 in CD11b-enriched cells. […] The viral entry molecules ACE2 and TMPRSS2 are expressed in the ileum and colon. […] Patients with IBD do not have higher expression during inflammation; medical therapy is associated with lower levels of ACE2.
32333836 We have previously provided the first genetic evidence that angiotensin converting enzyme 2 (ACE2) is the critical receptor for severe acute respiratory syndrome coronavirus (SARS-CoV), and ACE2 protects the lung from injury, providing a molecular explanation for the severe lung failure and death due to SARS-CoV infections. […] ACE2 has now also been identified as a key receptor for SARS-CoV-2 infections, and it has been proposed that inhibiting this interaction might be used in treating patients with COVID-19. […] However, it is not known whether human recombinant soluble ACE2 (hrsACE2) blocks growth of SARS-CoV-2. […] Here, we show that clinical grade hrsACE2 reduced SARS-CoV-2 recovery from Vero cells by a factor of 1,000-5,000. […] An equivalent mouse rsACE2 had no effect. […] We also show that SARS-CoV-2 can directly infect engineered human blood vessel organoids and human kidney organoids, which can be inhibited by hrsACE2. […] These data demonstrate that hrsACE2 can significantly block early stages of SARS-CoV-2 infections.
32333993 Potential underlying mechanisms such as: (i) a compromised half-live of the virus caused by the high-altitude environment, and (ii) a hypoxia mediated down regulation of angiotensin-converting enzyme 2 (ACE2), which is the main binding target of SARS-CoV-2 virus in the pulmonary epithelium are discussed.
32334082 In this study, we explored the expression and distribution of angiotensin-converting enzyme 2 (ACE2), the receptor of SARS-CoV-2, in the pancreas.
32335281 This brief article discusses the therapeutic potential of glycyrrhizin for the treatment of COVID-19 from the perspective of its pharmacological action, including binding angiotensin-converting enzyme II (ACE2), downregulating proinflammatory cytokines, inhibiting the accumulation of intracellular reactive oxygen species (ROS), inhibiting thrombin, inhibiting the hyperproduction of airway exudates, and inducing endogenous interferon.
32335334 We could identify mutational hotspots which appear to be major drivers of diversity among strains, with RBD of spike protein emerging as the key region involved in interaction with ACE2 and consequently a major determinant of infection outcome.
32335337 Furthermore, animal studies have shown that the ACE2 receptor is a potential pathway for host infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19.
32335456 The pathogenic infectivity of the virus requires the S1 subunit of the spike (S) protein to bind the host cell receptor, angiontensin converting enzyme (ACE2).
32336612 Angiotensin converting enzyme-2 (ACE2) receptors mediate the entry into the cell of three strains of coronavirus: SARS-CoV, NL63 and SARS-CoV-2. […] ACE2 receptors are ubiquitous and widely expressed in the heart, vessels, gut, lung (particularly in type 2 pneumocytes and macrophages), kidney, testis and brain. […] ACE2 is mostly bound to cell membranes and only scarcely present in the circulation in a soluble form. […] An important salutary function of membrane-bound and soluble ACE2 is the degradation of angiotensin II to angiotensin1-7. […] Consequently, ACE2 receptors limit several detrimental effects resulting from binding of angiotensin II to AT1 receptors, which include vasoconstriction, enhanced inflammation and thrombosis. […] Unfortunately, the entry of SARS-CoV2 into the cells through membrane fusion markedly down-regulates ACE2 receptors, with loss of the catalytic effect of these receptors at the external site of the membrane. […] Clinical reports of patients infected with SARS-CoV-2 show that several features associated with infection and severity of the disease (i.e., older age, hypertension, diabetes, cardiovascular disease) share a variable degree of ACE2 deficiency. […] We suggest that ACE2 down-regulation induced by viral invasion may be especially detrimental in people with baseline ACE2 deficiency associated with the above conditions. […] The additional ACE2 deficiency after viral invasion might amplify the dysregulation between the ‘adverse’ ACE→Angiotensin II→AT1 receptor axis and the ‘protective’ ACE2→Angiotensin1-7→Mas receptor axis. […] In this setting, recombinant ACE2, angiotensin1-7 and angiotensin II type 1 receptor blockers could be promising therapeutic approaches in patients with SARS-CoV-2 infection.
32337769 Inactivation of ACE2 during virus fusion into the host cell may be one of the underlying reasons for intense immunological reaction seen in the lung tissue.
32338224 Evidence has been provided that SARSCoV proteins are cleaved into two subunits, S1 and S2, respectively, and the amino acids 318-510 of the S1 represent the receptor-binding domain (RBD) which binds to ACE2 [10, 11]. […] Quite importantly, in the context of RBD there is the receptor-binding motif (RBM) (amino acids 424- 494), which accounts for complete binding to ACE2 [11]. […] In this respect, the sequence of COVID-19 RBM is similar to that of SARSCoV, thus, implicating that ACE2 may represent the binding receptors for COVID-19. […] Furthermore, gln493 residue of COVID-19 RBM seems to allow interaction with human ACE2, thus, suggesting the ability of this virus to infect human cells. […] According, to Wan and associates structural analysis [14], COVID-19 binds to human ACE2 with a lesser efficiency than human SARS-CoV (2002) but with higher affinity than human SARS-CoV (2003). […] Furthermore, same authors predicted that a single mutation at the 501 position may enhance the COVID-19 RBD binding capacity to human ACE2 and this evolution should be monitored in infected patients [14]. […] From a pathogenic point of view, evidence has been provided that binding of S2 to ACE2 receptor leads to its down-regulation with subsequent lung damage in the course of SARS-CoV infection [17]. […] Down-regulation of ACE2 causes excessive production of angiotensin (ANG) II by the related enzyme ACE with stimulation of ANG type 1a receptor (AT1R) and enhanced lung vascular permeability [18]. […] In particular, same authors have reported that recombinant ACE2 could attenuate severe acute lung injury in mice [18]. […] Moreover, Battle and associates [19] also proposed to use already available recombinant ACE2 for intercepting COVID-19 and attenuating infection. […] In the previous paragraphs, the presence of ACE2 on immune cells has been pointed out and, by analogy to epithelial cells, this receptor may also be down-regulated following viral entry. […] Therefore, in CoV-infected animal models and in infected humans further investigations are required to clarify a possible reduced expression of ACE2 on immune cells. […] There is evidence that ACE2 protects from severe acute lung failure and operates as a negative regulator of the renin-angiotensin system (RAS) [18, 37]. […] ACE2 counterbalances the noxious effects exhibited by ANG II and AT1R via activation of AT2R which arrests cell growth, inflammation and fibrosis [39]. […] In fact, losartan as well as olmesartan, used for treating hypertension in patients, were able to increase ACE2 expression after 28 days treatment of rats with myocardial infarction [41]. […] Taken together, these evidences suggest that CoV-induced down-regulation of ACE2 activates RAS with collateral damage to organs, such as lungs, in the course of SARS-related pneumonia. […] Then, putative therapeutic measures aimed at increasing ACE2 levels on respiratory epithelial cells should be taken into serious consideration. […] In all these experimental models, RES led to an increase of ACE2 with reduction of organ damage, such as liver steatosis and aorta media thickness and decrease of adipose tissue mass, respectively. […] In turn, Sirt1 down-regulates AT1R expression via ACE2 up-regulation [43, 48]. […] The data above discussed strongly suggest, that RES, as an activators of ACE2, should be investigated in animal models of CoV-induced severe pneumonia, also taking into account the antioxidant, anti-inflammatory and immunomodulating effects exerted by polyphenols [49]. […] From a pharmacologic point of view, RAS inhibition leads to upregulation of ACE2, thus, attenuating acute respiratory syndrome and myocarditis in COVID-19-infected patients. […] Conversely, increase in ACE2 expression may facilitate the access into the host of COVID-19, thus, aggravating the clinical picture. […] In fact, there are no available data which support that ACE inhibitors or ANG II type I receptor blockers increase COVID-19 infection via its binding to ACE2. […] Finally, Kuster and associates [52] write that there are no data on the strict relationship between ACE2 activity and SARS-CoV2 mortality. […] Moreover, in the SARSCoV2, cells expressing ACE2 were not attacked by the virus, while cells lacking ACE2 were bound by the SARS-CoV2 virus [53]. […] These findings suggest that also in the case of RES effects on COVID-19 infection, the dual role of ACE2 should be taken into serious consideration.
32338605 SARS-CoV-2 enters the cell via ACE2 that next to its role in RAAS is needed to inactivate des-Arg9 bradykinin, the potent ligand of the B1R. […] Without ACE2 acting as a guardian to inactivate the ligands of B1R, the lung environment is prone for local vascular leakage leading to angioedema. […] The SARS-CoV-2 virus, which causes COVID-19, enters the lining of the lungs via an enzyme called the ACE2 receptor, which is present on the outer surface of the lungs’ cells. […] The related coronavirus that was responsible for the SARS outbreak in the early 2000s also needs the ACE2 receptor to enter the cells of the lungs. […] In SARS, the levels of ACE2 in the lung decline during the infection. […] Studies with mice have previously revealed that a shortage of ACE2 leads to increased levels of a hormone called angiotensin II, which regulates blood pressure. […] However, other mouse studies have shown that ACE2 protects against a build-up of fluid in the lungs caused by a different molecule made by the body. […] It belongs to a family of molecules known as kinins, and ACE2 is known to inactivate certain kinins. […] This led van de Veerdonk et al. to propose that the excess of fluid in the lungs seen in COVID-19 patients may be because kinins are not being neutralized due to the shortage of the ACE2 receptor.
32339157 Angiotensin-converting enzyme 2 (ACE2) is a member of the renin-angiotension system, however, the correlation between ACE2 and prognosis in UCEC (Uterine Corpus Endometrial Carcinoma) and KIRP (Kidney Renal Papillary Cell Carcinoma) is not clear. […] We analyzed the expression levels of ACE2 in the Oncomine and TIMER databases, the correlation between ACE2 and overall survival in the PrognoScan, GEPIA and Kaplan-Meier plotter databases. […] The correlation between ACE2 and immune infiltration level and the type markers of immune cells was investigated in TIMER database. […] A prognosis analysis based on the expression levels of ACE2 was further performed in related immune cells subgroup. […] The ACE2 promoter methylation profile was tested in the UALCAN database. […] In addition, we used GSE30589 and GSE52920 databases to elucidate the changes of ACE2 expression in vivo and in vitro after SARS-CoV infection. […] ACE2 was elevated in UCEC and KIRP, and high ACE2 had a favorable prognosis. […] The expression of ACE2 was positively correlated with the level of immune infiltration of macrophage in KIRP, B cell, CD4+T cell, neutrophil and dendritic cell immune infiltration levels in UCEC. […] ACE2 was significantly positively correlated with the type markers of B cells and neutrophils, macrophages in UCEC, while ACE2 in KIRP was positively correlated with the type markers of macrophages. […] High ACE2 expression level had a favorable prognosis in different enriched immune cells subgroups in UCEC and KIRP. […] And the promoter methylation levels of ACE2 in UCEC and KIRP were significantly reduced. […] What’s more, we found that the expression of ACE2 decreased in vivo and in vitro after SARS-CoV infection. […] In conclusion, ACE2 expression increased significantly in UCEC and KIRP, elevated ACE2 was positively correlated with immune infiltration and prognosis.
32339344 Angiotensin-converting enzyme 2 (ACE2) is a cellular receptor for COVID-19.
32339391 Expression of angiotensin-converting enzyme 2 (ACE2 - the functional receptor for SARS-CoV) - is upregulated in adipocytes of obese and diabetic patients, which turns adipose tissue into a potential target and viral reservoir.
32341442 Recently, angiotensin-converting enzyme 2 (ACE2) has been shown to be a functional receptor for SARS-CoV-2 to enter host target cells. […] Given that angiotensin receptor blockers (ARBs) and an ACE inhibitor (ACEI) upregulated ACE2 expression in animal studies, the concern might arise regarding whether ARBs and ACEIs would increase the morbidity and mortality of COVID-19.
32343658 Because the virus enters human cells by way of the membrane-associated angiotensin converting enzyme 2 (ACE2), keeping the virus from docking to this receptor is a conceivable treatment approach.
32344305 In the literature, SARS-CoV has been known to cause de novo diabetes by ACE2-dependent uptake on pancreatic isle cells, and furthermore dysregulate lipid autophagy in favor of the viral lifecycle.
32345124 From the binding energy and interaction studies, the Saikosaponins U and V showed the best affinity towards both the proteins suggesting them to be future research molecule as they mark the desire interaction with NSP15, which is responsible for replication of RNA and also with 2019-nCoV spike glycoprotein which manage the connection with ACE2.
32345140 The current study aimed to repurpose stilbenoid analogs, reported for some other biological activities, against SARS-CoV-2 spike protein and human ACE2 receptor complex for their affinity and stability using molecular dynamics simulation and binding free energy analysis based on molecular docking. […] However, fifty nanoseconds molecular dynamic simulation in aqueous solution revealed highly stable bound conformation of resveratrol to the viral protein: ACE2 receptor complex. […] SarmaHighlightsStilbenoid analogs could be potential disruptors of SARS-CoV-2 spike protein and human ACE2 receptor complex.In particular, resveratrol revealed highly stable conformation to the viral protein: ACE2 receptor complex.The strong interaction of resveratrol is affirmed by molecular dynamic simulation studies and better net free energies.
32345328 In this study, we investigated the gene expression of angiotensin I-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) with prognosis in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC).
32345362 SARS-CoV-2, which is the virus causing coronavirus disease 2019 (COVID-19), uses the angiotensin-converting enzyme 2 (ACE2) as a cell receptor to invade human cells. […] Thus, ACE2 is the key to understanding the mechanism of SARS-CoV-2 infection. […] This study is to investigate the ACE2 expression in various human tissues in order to provide insights into the mechanism of SARS-CoV-2 infection. […] We compared ACE2 expression levels across 31 normal human tissues between males and females and between younger (ages ≤ 49 years) and older (ages > 49 years) persons using two-sided Student’s t test. […] We also investigated the correlations between ACE2 expression and immune signatures in various tissues using Pearson’s correlation test. […] ACE2 expression levels were the highest in the small intestine, testis, kidneys, heart, thyroid, and adipose tissue, and were the lowest in the blood, spleen, bone marrow, brain, blood vessels, and muscle. […] ACE2 showed medium expression levels in the lungs, colon, liver, bladder, and adrenal gland. […] ACE2 was not differentially expressed between males and females or between younger and older persons in any tissue. […] In the skin, digestive system, brain, and blood vessels, ACE2 expression levels were positively associated with immune signatures in both males and females. […] In the thyroid and lungs, ACE2 expression levels were positively and negatively associated with immune signatures in males and females, respectively, and in the lungs they had a positive and a negative correlation in the older and younger groups, respectively. […] This study provides new insights into the role of ACE2 in the SARS-CoV-2 pandemic.
32348052 ACE inhibitors and sartans upregulate the expression of angiotensin-converting enzyme 2 (ACE2), the pulmonary receptor for SARS-CoV-2. […] Les IEC et les sartans modulent l’expression de l’enzyme de conversion de l’angiotensine 2 (ACE2), récepteur pulmonaire du SARS-CoV-2.
32348166 With the capability of inducing elevated expression of ACE2, the cellular receptor for SARS-CoV-2, angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors (ARBs/ACEIs) treatment may have a controversial role in both facilitating virus infection and reducing pathogenic inflammation.
32348692 Angiotensin converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) mediate viral infection of host cells. […] We reasoned that differences in ACE2 or TMPRSS2 gene expression in sputum cells among asthma patients may identify subgroups at risk for COVID19 morbidity. […] We analyzed gene expression for ACE2 and TMPRSS2, and for intercellular adhesion molecule 1 (ICAM-1)(rhinovirus receptor as a comparator), in sputum cells from 330 participants in the Severe Asthma Research Program-3 and 79 healthy controls. […] Gene expression of ACE2 was lower than TMPRSS2, and expression levels of both genes was similar in asthma and health. […] Among asthma patients, male gender, African Americans race, and history of diabetes mellitus, was associated with higher expression of ACE2 and TMPRSS2. […] Use of inhaled corticosteroids (ICS) was associated with lower expression of ACE2 and TMPRSS2, but treatment with triamcinolone acetonide (TA) did not decrease expression of either gene. […] Higher expression of ACE2 and TMPRSS2 in males, African Americans, and patients with diabetes mellitus provides rationale for monitoring these asthma subgroups for poor COVID19 outcomes. […] The lower expression of ACE2 and TMPRSS2 with ICS use warrants prospective study of ICS use as a predictor of decreased susceptibility to SARS-CoV-2 infection and decreased COVID19 morbidity.
32349031 It’s reported that the entry receptor of SARS-CoV-2 has been confirmed to be angiotensin converting enzymes 2 (ACE2). […] Notably, whether the ACE-related inhibitors or drugs modulated ACE2 activity in affecting with viral activity and disease severity of SARS-CoV-2 is still an open question.
32350632 SARS-CoV2, the virus responsible for COVID-19, enters the cell via ACE2 expressed in select organs.
32351121 Extensive research ensuing the outbreak of coronavirus-related severe acute respiratory syndrome in the year 2003, and COVID-19 recently revealed a role of renin-angiotensin system (RAS) components in the entry of coronavirus wherein angiotensin-converting enzyme 2 (ACE2) had garnered the significant attention. […] In this brief review, we will elaborate on the role of RAS and ACE2 in pathogenesis of COVID-19.
32352535 Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) -a homologue of ACE-to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes. […] While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis. […] Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed.
32353982 They are represented by the dynamism of the ocular surface system (e.g., the tear film turnover) and the distribution of ACE2 receptors and TMPRSS2 protein.
32354022 SARS-CoV-2 exploits ACE2 for host cell entry. […] ACE2 plays an essential role in the renin-angiotensin-aldosterone system (RAAS), which regulates blood pressure and fluid balance. […] ACE2 also protects organs from inflammatory injuries and regulates intestinal functions. […] ACE2 can be shed by two proteases, ADAM17 and TMPRSS2. […] TMPRSS2-cleaved ACE2 allows SARS-CoV-2 cell entry, whereas ADAM17-cleaved ACE2 offers protection to organs. […] SARS-CoV-2 infection-caused ACE2 dysfunction worsens COVID-19 and could initiate multi-organ failure. […] Here, we will explain the role of ACE2 in the pathogenesis of severe and critical conditions of COVID-19 and discuss auspicious strategies for controlling the disease.
32356628 There is concern about the potential of an increased risk related to medications that act on the renin-angiotensin-aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2).
32356926 The SARS-CoV-2 virus enters the airway and binds, by means of the S protein on its surface to the membrane protein ACE2 in type 2 alveolar cells. […] The S protein-ACE2 complex is internalized by endocytosis leading to a partial decrease or total loss of the enzymatic function ACE2 in the alveolar cells and in turn increasing the tissue concentration of pro-inflammatory angiotensin II by decreasing its degradation and reducing the concentration of its physiological antagonist angiotensin 1-7.
32358202 Indeed, the SARS-CoV-2 receptor angiotensin converting enzyme 2 (ACE2) is highly expressed on differentiated enterocytes.
32360480 Such drugs comprise inhibitors of TMPRSS2 serine protease and inhibitors of angiotensin-converting enzyme 2 (ACE2). […] Blockade of ACE2, the host cell receptor for the S protein of SARS-CoV-2 and inhibition of TMPRSS2, which is required for S protein priming may prevent cell entry of SARS-CoV-2.
32360608 The purpose of this article is to review and investigate further the molecular mechanism by which the SARS-CoV2 virus infection proceeds via the formation of a hetero-trimer between its protein S, the ACE2 receptor and the B0AT1 protein, which is the “entry receptor” for the infection process involving membrane fusion (Li et al., 2003).
32360703 The wide range of affected organs is presumably based on the common expression of the major SARS-CoV-2 entry-receptor angiotensin-converting enzyme 2 (ACE2). […] Physiologically, ACE2 degrades angiotensin II, the master regulator of the renin-angiotensin-aldosterone system (RAAS), thereby converting it into vasodilatory molecules, which have well-documented cardio-protective effects. […] Thus, RAAS inhibitors, which may increase the expression levels of ACE2, are commonly used for the treatment of hypertension and CVD. […] This, and the fact that SARS-CoV-2 hijacks ACE2 for cell-entry, have spurred controversial discussions on the role of ACE2 in COVID-19 patients. […] In this review, we highlight the state-of-the-art knowledge on SARS-CoV-2-dependent mechanisms and the potential interaction with ACE2 expression and cell surface localization.
32361098 The target of 2019-nCoV and severe acute respiratory syndrome coronavirus (SARS-CoV) is angiotensin-converting enzyme 2 (ACE2) positive cells. […] ACE2 is present in the salivary gland duct epithelium, and thus it could be the target of 2019-nCoV and SARS-CoV. […] SARS-CoV-related animal model experiments show that it can infect the epithelial cells on the salivary gland duct in Chinese rhesus macaques by targeting ACE2.
32361911 Angiotensin-converting enzyme 2 (ACE2), reported as a SARS-CoV-2 receptor, is also expressed in human male testes. […] However, the characteristics of ACE2-positive cells and the expression of other SARS-CoV-2 process-related genes are still worthy of further investigation. […] We found that ACE2 expressing cells existed in almost all testis cell types and Sertoli cells had highest expression level and positive cells ratio. […] Moreover, ACE2 was also expressed in human male PGCs. […] In adulthood, the level of ACE2 expression decreased with the increase of age. […] We also found that ACE2 positive cells had high expressions of stress response and immune activation-related genes. […] Furthermore, ACE2 expression level in NOA donors’ Sertoli cells was significantly decreased.
32362217 The objective of this present study is to focus on the in silico study to screen for an alternative drug that can block the activity of the angiotensin converting enzyme 2 (ACE2) as a receptor for SARS-CoV-2, potential therapeutic target of the COVID-19 virus using natural compounds (Isothymol, Thymol, Limonene, P-cymene and γ-terpinene) derived from the essential oil of the antiviral and antimicrobial plant Ammoides verticillata (Desf.) […] This study reveals that Isothymol, a major component of this plant, gives the best docking scores, compared to, the co-crystallized inhibitor β-D-mannose of the enzyme ACE2, to Captropil drug as good ACE2 inhibitor and to Chloroquine antiviral drug also involved in other mechanisms as inhibition of ACE2 cellular receptor. In silico (ADME), drug-likeness, PASS & P450 site of metabolism prediction, pharmacophore Mapper showed that the compound Isothymol has given a good tests results compared to the β-D-mannose co-crystallized inhibitor, to Captopril and Chloroquine drugs. […] The Molecular Dynamics Simulation study showed good result for the Isotymol- ACE2 docked complex. […] This study revealed for the first time that Isothymol is a functional inhibitor of angiotensin converting enzyme 2 activity and the components of essential oils Ammoides verticillata can be used as potential inhibitors to the ACE2 receptor of SARS-CoV-2.
32363137 •There is no enough evidence to indicate that ACEIs and ARBs result in ACE2 upregulation. […] •The level of ACE2 expression is not completely related with the risk of COVID-19 infection.
32363255 For the first time, using the molecular docking technique, we report the inhibitory effect of the considered compounds on the host receptor angiotensin-converting enzyme 2 (ACE2) protein in the human body that leads to a crucial foundation about coronavirus resistance of individual compounds on the main protease (PDB6LU7) protein of SARS-CoV-2. […] The results show that the 17 organosulfur compounds, accounting for 99.4% contents of the garlic essential oil, have strong interactions with the amino acids of the ACE2 protein and the main protease PDB6LU7 of SARS-CoV-2. […] Interestingly, docking results indicate the synergistic interactions of the 17 substances, which exhibit good inhibition of the ACE2 and PDB6LU7 proteins.
32364961 To enter airway and lung epithelia, SARS-CoV-2 attaches to ACE2 receptors by spike (S) glycoproteins. […] Molecular mechanisms that promote interaction between SARS-CoV-2 virus and host with particular focus on virus cell entry receptor ACE2 are described.
32365180 The virus invades the target cell by binding to angiotensin-converting enzyme (ACE) 2 and modulates the expression of ACE2 in host cells. […] ACE2, a pivotal component of the renin-angiotensin system, exerts its physiological functions by modulating the levels of angiotensin II (Ang II) and Ang-(1-7). […] We reviewed the literature that reported the distribution and function of ACE2 in the female reproductive system, hoping to clarify the potential harm of 2019-nCoV to female fertility. […] The available evidence suggests that ACE2 is widely expressed in the ovary, uterus, vagina and placenta. […] Ang II, ACE2 and Ang-(1-7) regulate follicle development and ovulation, modulate luteal angiogenesis and degeneration, and also influence the regular changes in endometrial tissue and embryo development. […] Taking these functions into account, 2019-nCoV may disturb the female reproductive functions through regulating ACE2.
32365214 There is a pool of coronavirus among bats which have the potential to infect humans through the ACE2 receptor, and new human epidemics can be expected.
32365751 To gain insight into the high infection rate of the SARS-CoV-2 virus, we compare the interaction between the human ACE2 receptor and the SARS-CoV-2 spike protein with that of other pathogenic coronaviruses using molecular dynamics simulations. […] SARS-CoV, SARS-CoV-2, and HCoV-NL63 recognize ACE2 as the natural receptor but present a distinct binding interface to ACE2 and a different network of residue-residue contacts. […] The SARS-CoV-2-ACE2 complex contains a higher number of contacts, a larger interface area, and decreased interface residue fluctuations relative to the SARS-CoV-ACE2 complex.
32366279 In addition, the expression of angiotensin converting enzyme 2 (ACE2), the receptor of COVID-19, were aberrantly expressed in many tumors. […] However, a systematic analysis of ACE2 aberration remained to be elucidated in human cancers. […] Here, we analyzed genetic alteration, RNA expression, and DNA methylation of ACE2 across over 30 tumors. […] Notably, overexpression of ACE2 have been observed in including colon adenocarcinoma (COAD), kidney renal papillary cell carcinoma (KIRP), pancreatic adenocarcinoma (PAAD), rectum adenocarcinoma (READ), stomach adenocarcinoma (STAD), and lung adenocarcinoma (LUAD). […] In addition, hypo DNA methylation of ACE2 has also been identified in most of these ACE2 highly expressed tumors. […] Conclusively, our study for the first time curated both genetic and epigenetic variations of ACE2 in human malignancies.
32366740 A concern was raised regarding the safety of ibuprofen use because of its role in increasing ACE2 levels within the Renin-Angiotensin-Aldosterone system. […] ACE2 is the coreceptor for the entry of SARS-CoV-2 into cells, and so, a potential increased risk of contracting COVID-19 disease and/or worsening of COVID-19 infection was feared with ibuprofen use. […] However, available data from limited studies show administration of recombinant ACE2 improves lung damage caused by respiratory viruses, suggesting ibuprofen use may be beneficial in COVID-19 disease.
32368531 To penetrate the body, Severe acute respiratory syndrome coronavirus 2 uses ACE2 receptors, which are present not only in respiratory epithelium but also in gastrointestinal mucosa and liver cholangiocytes.
32369211 Angiotensin-converting enzyme 2 (ACE2) removes a single residue from Ang I to yield Ang (1-9) and cleaves a single residue from Ang II to generate Ang (1-7). […] Thus ACE2 counterbalances ACE function decreasing Ang II levels1 .
32370986 Since the ACE2 (angiotensin-converting enzyme 2) enzyme is the receptor that allows SARS COV2 entry into cells, the fear was that pre-existing treatment with ACEi or ARB might increase the risk of developing severe or fatal severe acute respiratory syndrome in case of COVID-19 infection. […] ACE2 is a membrane-bound enzyme (carboxypeptidase) that contributes to the inactivation of angiotensin II and therefore physiologically counters angiotensin II effects. […] ACEis do not inhibit ACE2. […] Although ARBs have been shown to up-regulate ACE2 tissue expression in experimental animals, evidence was not always consistent in human studies. […] Moreover, to date there is no evidence that ACEi or ARB administration facilitates SARS-COV2 cell entry by increasing ACE2 tissue expression in either animal or human studies. […] Finally, some studies support the hypothesis that elevated ACE2 membrane expression and tissue activity by administration of ARB and/or infusion of soluble ACE2 could confer protective properties against inflammatory tissue damage in COVID-19 infection.
32373991 The phytochemical library was subjected to virtual screening against molecular targets; Main protease (Mpro) and Angiotensin-Converting Enzyme 2 (ACE2).
32374416 The relationship between Renin-Angiotensin system (RAS) and COVID-19 pandemic and, in particular, RAS as part of the CoV-2 infection process via Angiotensin Converting Enzyme 2 (ACE2), the entry point of SARS-CoV-2, has resulted in conflicting suggestions regarding how RAS and its role(s) should inform treating COVID-19. […] ACE inhibitors or angiotensin II (Ang)-type 1 receptor blockers (ARBs), in fact, have been suggested to be avoided as they potentially upregulate ACE2 1 and, conversely, there are suggestions that ARBs might be beneficial 2 as SARS-CoV-2 causing ACE2 downregulation slows the Ang II conversion to the vasodilatory, anti-inflammatory, antioxidant and antiatherosclerotic Ang 1-7 3-5 , and the use of ARBs by blocking the excessive Ang II type-1 receptors activation, would be beneficial upregulating ACE2 activity and increasing Ang 1-7 levels.
32374427 SARS-CoV-2 is assumed to use angiotensin-converting enzyme 2 (ACE2) and other auxiliary proteins for cell entry. […] However, it is currently unclear whether conjunctival epithelial cells express ACE2 and its cofactors. […] In this study, a total of 38 conjunctival samples from 38 patients, including 12 healthy conjunctiva, 12 melanoma, 7 squamous cell carcinoma and 7 papilloma samples, were analyzed using high-throughput RNA sequencing to assess mRNA expression of the SARS-CoV-2 receptor ACE2 and its cofactors including TMPRSS2, ANPEP, DPP4, and ENPEP. […] ACE2 protein expression was assessed in eight healthy conjunctival samples using immunohistochemistry. […] Our results show that the SARS-CoV-2 receptor ACE2 is not substantially expressed in conjunctival samples on the mRNA (median 0.0 transcripts per million (TPM), min 0.0 TPM, max 1.7 TPM) and protein levels. […] In conclusion, this study finds no evidence for a significant expression of ACE2 and its auxiliary mediators for cell entry in conjunctival samples, making conjunctival infection with SARS-CoV-2 via these mediators unlikely.
32374430 The current pandemic and its pleotropic effects can be explained in part by interaction between SARS-CoV-2 spike protein S, the ACE2/L-SIGN/CD209 receptor on the type II alveolar cell of the lung, and the DC-SIGN receptor on the respiratory dendritic cell (DC) and associated endothelial cells.
32375085 Acting as the receptor for SARS-CoV entering mammalian cells, angiotensin converting enzyme-2 (ACE2) plays a pivotal role in the regulation of cardiovascular cell function.
32376368 Additionally, the key targets of SARS-COV-2, namely 3CL hydrolase (Mpro) and angiotensin-converting enzyme 2(ACE2), were used to dock the main ingredients from the 40 kinds by the LigandFitDock method.
32376627 In this study, we firstly verified that SARS-CoV-2 uses human ACE2 as a cell receptor and its spike (S) protein mediates high membrane fusion activity.
32376634 To fulfill its function, SARS-CoV-2 spike binds to its receptor human ACE2 (hACE2) through its receptor-binding domain (RBD) and is proteolytically activated by human proteases. […] First, SARS-CoV-2 RBD has higher hACE2 binding affinity than SARS-CoV RBD, supporting efficient cell entry. […] Second, paradoxically, the hACE2 binding affinity of the entire SARS-CoV-2 spike is comparable to or lower than that of SARS-CoV spike, suggesting that SARS-CoV-2 RBD, albeit more potent, is less exposed than SARS-CoV RBD. […] The high hACE2 binding affinity of the RBD, furin preactivation of the spike, and hidden RBD in the spike potentially allow SARS-CoV-2 to maintain efficient cell entry while evading immune surveillance.
32376714 The RBD of spike protein S binds to Angiotensin Converting Enzyme 2 (ACE2) to initiate cellular entry. […] The spike protein of SARS-CoV-2 shows more than 90% amino acid similarity to the pangolin and bat CoVs and these also use ACE2 as a receptor. […] Binding of the spike protein to ACE2 exposes the cleavage sites to cellular proteases.
32378030 The SARS-CoV-2 virus binds to angiotensin-converting enzyme 2 (ACE2) present on brain endothelial and smooth muscle cells. […] ACE2 is a key part of the renin angiotensin system (RAS) and a counterbalance to angiotensin-converting enzyme 1 (ACE1) and angiotensin II. […] Depletion of ACE2 by SARS-CoV-2 may tip the balance in favor of the “harmful” ACE1/angiotensin II axis and promote tissue injury including stroke.
32378705 Spike (S) protein, one of the structural proteins of this virus plays key role in receptor (ACE2) binding and thus virus entry.
32379346 The paper of Cheng H. et al., describes an interesting hypothesis regarding the organ protective effects of ACE2 activation against the malignant effects of SARS-CoV-2 infection in humans, and describes interesting previous results reporting ACE2 higher levels in children, young people and women that is coincident with a lower morbidity and health problems associated to COVID19. […] In the present comment the treatment of COVID19 patients with ACE2 activators, such as diminazene aceturate (DIZE), which are currently used as antiparasitic drugs, is proposed.
32379417 We show that the cell surface protein ACE2 and the protease TMPRSS2 are expressed in sustentacular cells of the olfactory epithelium but not, or much less, in most olfactory receptor neurons.
32380511 Because angiotensin-converting enzyme 2 (ACE2) is the cell entry receptor of SARS-CoV5, we used transgenic mice bearing human ACE2 and infected with SARS-CoV-2 to study the pathogenicity of the virus. […] Weight loss and virus replication in lung were observed in hACE2 mice infected with SARS-CoV-2. […] Notably, we have confirmed the pathogenicity of SARS-CoV-2 in hACE2 mice.
32380565 · Immature angiotensin converting enzyme (ACE2) interferes with coronavirus entry into the cells..
32380903 Despite initial findings indicating that SARS-CoV and SARS-CoV-2 are genetically related belonging to the same virus species and that the two viruses used the same entry receptor, angiotensin-converting enzyme 2 (ACE2), our data demonstrated that there is no detectable cross-neutralization by SARS patient sera against SARS-CoV-2.
32382146 To determine the expressions of SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2) genes in human and mouse ocular cells and comparison to other tissue cells. […] The expression of ACE2 and TMPRSS2 genes was determined in human primary conjunctival and pterygium cells, human ocular and other tissue cell lines, mesenchymal stem cells as well as mouse ocular and other tissues by reverse transcription-polymerase chain reaction (RT-PCR) and SYBR green PCR. […] RT-PCR analysis showed consistent expression by 2 ACE2 gene primers in 2 out of 3 human conjunctival cells and pterygium cell lines. […] In addition, mouse cornea had comparable expression of Tmprss2 gene and lower but prominent Ace2 gene expression compared with the lung tissue. […] Considering the necessity of both ACE2 and TMPRSS2 for SARS-CoV-2 infection, our results suggest that conjunctiva would be less likely to be infected by SARS-CoV-2, whereas pterygium possesses some possibility of SARS-CoV-2 infection. […] With high and consistent expression of Ace2 and Tmprss2 in cornea, cornea rather than conjunctiva has higher potential to be infected by SARS-CoV-2.
32383269 In this connection, the present in silico study aims to understand the sequence divergence of spike protein (the major infective protein of SARS-CoV-2), its mode of interaction with the angiotensin-converting enzyme-2 receptor (ACE2) receptor of human and related animal hosts/reservoir. […] Our data indicated that the spike glycoprotein of SARS-CoV-2 is phylogenetically close to bat coronavirus and strongly binds with ACE2 receptor protein from both human and bat origin. […] Finally, this study is expected to improve our understanding on the immunobiology of SARS-CoV-2 and could be useful in adopting spike protein, ACE2, or TLR-guided intervention strategy against COVID-19 shortly.
32383624 This might be due to the fact that ACE2 is the receptor for the virus to enter human cells, but, on the contrary, that ACE2 expression is downregulated following SARS-1 infection, resulting in disproportionate activation of renin-angiotensin-aldosterone system and exacerbated pneumonia progression.
32384820 Here, we detailed how to effectively pseudotype lentiviral particles with SARS-CoV-2 Spike and infect 293T cells engineered to express the SARS-CoV-2 receptor, ACE2.
32387456 Cell entry of SARS-CoV-2 depends on binding of the viral spike (S) proteins to ACE2 and on S protein priming by TMPRSS2.
32388330 The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes angiotensin-converting enzyme II (ACE2) receptor for host cell entry.
32388331 Compromised innate immunity, pro-inflammatory cytokine milieu, reduced expression of ACE2 and use of renin-angiotensin-aldosterone system antagonists in people with diabetes mellitus contribute to poor prognosis in COVID-19.
32388451 Recent reports suggest that ACE2, which is the target protein to invade the host, has a ubiquitous presence in human organs, including lung parenchyma, gastrointestinal tract, nasal mucosa, renal and urinary tract, airway epithelia, lymphoid tissues, reproductive organs, vascular endothelium and neurons.
32388565 Angiotensin-converting enzyme 2 (ACE2) is a functional receptor for coronaviruses. […] Higher ACE2 concentrations might lead to increased vulnerability to SARS-CoV-2 in patients on RAAS inhibitors. […] We measured ACE2 concentrations in 1485 men and 537 women with heart failure (index cohort). […] The strongest predictor of elevated concentrations of ACE2 in both cohorts was male sex (estimate = 0.26, P < 0.001; and 0.19, P < 0.001, respectively). […] In the index cohort, use of ACE inhibitors, angiotensin receptor blockers (ARBs), or mineralocorticoid receptor antagonists (MRAs) was not an independent predictor of plasma ACE2. […] In the validation cohort, ACE inhibitor (estimate = -0.17, P = 0.002) and ARB use (estimate = -0.15, P = 0.03) were independent predictors of lower plasma ACE2, while use of an MRA (estimate = 0.11, P = 0.04) was an independent predictor of higher plasma ACE2 concentrations. […] In two independent cohorts of patients with heart failure, plasma concentrations of ACE2 were higher in men than in women, but use of neither an ACE inhibitor nor an ARB was associated with higher plasma ACE2 concentrations. […] These data might explain the higher incidence and fatality rate of COVID-19 in men, but do not support previous reports suggesting that ACE inhibitors or ARBs increase the vulnerability for COVID-19 through increased plasma ACE2 concentrations.
32389499 Here, we advance the hypothesis that four well-recognized features of aging contribute to the disproportionate SARS-CoV-2 mortality suffered by elderly men: i. the presence of subclinical systemic inflammation without overt disease, ii. a blunted acquired immune system and type I interferon response due to the chronic inflammation; iii. the downregulation of ACE2 (i.e. the SARS-CoV-2 receptor); and iv. accelerated biological aging.
32389847 ACE2 is a receptor of entry of SARS-CoV-2 into the host cells, and its upregulation has been implicated in increasing susceptibility of individuals to this infection. […] The clinical picture of COVID-19 suggests a role of ACE2 blockade, rather than its overexpression, in causing the pathogenesis. […] ACE2 blockade results in increased angiotensin II activity with simultaneous hampering of functions of angiotensin-(1-7)/MasR axis.
32390091 Immunohistochemical staining was used to detect the expressions of ACE2 in tissues. […] The ACE2 expression levels were up-regulated in patients of severe type and critically ill type. […] ACE2 may be the receptor of COVID-19.
32391169 Severe Acute Respiratory Syndrome-Coronavirus-1 and 2 viral surface protein is known to attach angiotensin converting enzyme 2 (ACE2) on the cell membrane to facilitate viral entry into the cytoplasm. […] Despite the theoretical concerns of increased ACE2 expression by Renin-Angiotensin-Aldosterone system (RAS) blockade, there is no evidence that RAS inhibitors are harmful during COVID-19 infection and have in fact been shown to be beneficial in animal studies.
32391242 Viral genomic sequencing has shown that SARS-CoV-2 spike protein utilizes angiotensin-converting enzyme 2 (ACE2) found on ciliated epithelial cells of the human lungs as its specific receptor.
32391742 Background Angiotensin converting enzyme 2 (ACE2), a target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), demonstrates its highest surface expression in the lung, small bowel, and vasculature, suggesting abdominal viscera may be susceptible to injury.
32392562 In this review, we provide the latest insights into the roles of angiotensin-converting enzyme II (ACE2) and Ang II receptor-1 (AT1-R) in this disease. […] Novel therapeutic strategies, including recombinant ACE2, ACE inhibitors, AT1-R blockers, and Ang 1-7 peptides, may prevent or reduce viruses-induced pulmonary, cardiac, and renal injuries. […] In addition to antiviral therapy, potential ACE2- and AT1-R-inhibiting strategies, and other supportive care, we suggest other potential JAKinibs and novel anti-inflammatory combination therapies that affect the JAK-STAT pathway in patients with COVID-19.
32392945 SARS-CoV通过结合血管紧张素转换酶2(ACE2)进入细胞,病变与病程相关,DAD渗出期一般见于病程10~14 d死亡患者。
32393136 SARS-CoV-2 possesses high-affinity for angiotensin converting enzyme 2 (ACE2) receptor, which is highly concentrated in the lungs and cardiovascular tissue, thereby provoking concern for cardiovascular involvement in COVID-19 cases.
32394467 Angiotensin-converting-enzyme 2 (ACE2) in soluble form as a recombinant protein can prevent the spread of coronavirus by restricting binding and entry. […] Favipiravir increases clinical recovery and reduces respiratory problems and has a stronger antiviral effect than LPV/r. currently, appropriate treatment for patients with COVID-19 is an ACE2 inhibitor and a clinical problem reducing agent such as favipiravir in addition to hydroxychloroquine and corticosteroids.
32394639 Cell binding and entry of betacoronaviruses is via their surface spike glycoprotein; SARS-CoV binds to the metalloprotease angiotensin-converting enzyme 2 (ACE2), MERS-CoV utilizes dipeptidyl peptidase 4 (DPP4), and recent modeling of the structure of SARS-CoV-2 spike glycoprotein predicts that it can interact with human DPP4 in addition to ACE2.
32395474 Angiotensin-converting enzyme 2 (ACE2) was recently identified to functional receptor of SARS-CoV-2. […] Previous experimental data revealed ACE2 level was increased following treatment with ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs).
32395525 The novel coronavirus 2019 (2019-nCoV) infected individuals by binding human angiotensin converting enzyme II (ACE2) receptor. […] ACE2 is widely expressed in multiple organs including respiratory, cardiovascular, digestive and urinary systems in healthy individuals. […] These tissues with high expression level of ACE2 seemed to be more vulnerable to SARS-CoV-2 infection. […] The tissue atlas database and the blood atlas were used to analyze the distribution of ACE2 in human tissues or organs of cancers and normal samples. […] Starbase dataset was applied to predict the prognosis of cancers according to expression level of ACE2. […] In this study, we demonstrated a landscape profiling analysis on expression level of ACE2 in pan-cancers and showed the risky of different type of cancers to SARS-CoV-2 according to the expression level of ACE2. […] In addition, we found that ACE2 was both differential expression and related to the prognosis only in liver hepatocellular carcinoma (LIHC). […] Relative high expression of ACE2 indicated a favorable prognosis in LIHC, but they might be more susceptible to SARS-CoV-2. […] We indeed emphasized that LIHC patients with high expression level of ACE2 should be more cautious of the virus infection.
32396773 Spike (S) glycoprotein is the structural protein of SARS-CoV-2 located on the envelope surface, involve in interaction with angiotensin converting enzyme 2 (ACE2), a cell surface receptor, followed by entry into the host cell. […] Thereby, blocking the S glycoprotein through potential inhibitor may interfere its interaction with ACE2 and impede its entry into the host cell. […] Here, we present a truncated version of human ACE2 (tACE2), comprising the N terminus region of the intact ACE2 from amino acid position 21-119, involved in binding with receptor binding domain (RBD) of SARS-CoV-2. […] We analyzed the in-silico potential of tACE2 to compete with intact ACE2 for binding with RBD. […] The protein-protein docking and molecular dynamic simulation showed that tACE2 has higher binding affinity for RBD and form more stabilized complex with RBD than the intact ACE2. […] Furthermore, prediction of tACE2 soluble expression in E. coli makes it a suitable candidate to be targeted for Covid-19 therapeutics.
32397951 The surface of host cells is covered by some receptors, known as ACE2, which mediates the binding and entry of CoV. […] A major step in exploring SARS-COV-2 pathogenesis is to determine the distribution of ACE2 proteins on tissue surface. […] In this review, the structure and origin of CoV, the role of ACE2 as a receptor of SARS-COV-2 on the surface of host cells, and the ACE2 distribution in different tissues with a focus on lung and cardiovascular system has been discussed.
32401442 ACE2 is not only an enzyme that counters the effects of the renin-angiotensin-aldosterone system (RAAS) but is also the entry receptor for SARS-CoV-2, the virus of the Covid-19 pandemic. […] Some experimental data suggest that ACE inhibitors and ARBs increase ACE2 levels, thus raising concerns on their security in Covid-19 positive patients. […] L’enzyme de conversion de l’angiotensine ACE2 est le récepteur membranaire du virus SARS-CoV-2, permettant son entrée dans les cellules cibles. […] ACE2 est également une enzyme qui contrebalance les effets de l’axe classique angiotensine II et récepteur AT1 du système rénine-angiotensine.
32401844 In addition, the virus uses angiotensin-converting enzyme (ACE) receptors, more precisely ACE2, to penetrate the cell; therefore, the use of ACE inhibitor drugs and angiotensin receptor blockers could cause an increase in these receptors, thus facilitating the entry of the virus into the cell.
32402766 During the infection of alveolar epithelial cells of the lung, the ACE2 receptor has a central function. […] The antimalarial drugs chloroquine phosphate (CQ) and hydroxychloroquine (HCQ) impair in vitro the terminal glycosylation of ACE2 without significant change of cell-surface ACE2 and, therefore, might be potent inhibitors of SARS-CoV-2 infections.
32403995 The SARS-CoV-2 infection relies on trimeric spike (S) proteins to facilitate virus entry into host cells by binding to ACE2 receptor on host cell membranes. […] From two llama VHH libraries, unique humanized VHHs that bind to S protein and block the S/ACE2 interaction were identified. […] Multi-specific antibodies with enhanced affinity and avidity, and improved S/ACE2 blocking are currently being developed using an in-silico approach that also fuses VHHs to Fc domains. […] Importantly, our current bi-specific antibody shows potent S/ACE2 blocking (KD - 0.25 nM, IC100 ∼ 36.7 nM, IC95 ∼ 12.2 nM, IC50 ∼ 1 nM) which is significantly better than individual monoclonal VHH-Fcs.
32404436 Here, we report productive infection of SARS-CoV-2 in ACE2+ mature enterocytes in human small intestinal enteroids.
32404477 B38 and H4 block the binding between virus S-protein RBD and cellular receptor ACE2. […] The RBD-B38 complex structure revealed that most residues on the epitope overlap with the RBD-ACE2 binding interface, explaining the blocking effect and neutralizing capacity.
32404529 Here, we used X-ray structures of human ACE2 bound to the receptor-binding domain (RBD) of the spike protein (S) from SARS-CoV-2 to predict its binding to ACE2 proteins from different animals, including pets, farm animals, and putative intermediate hosts of SARS-CoV-2. […] Comparing the interaction sites of ACE2 proteins known to serve or not serve as receptor allows to define residues important for binding. […] From the 20 amino acids in ACE2 that contact S up to seven can be replaced and ACE2 can still function as the SARS-CoV-2 receptor. […] Some ACE2 proteins even tolerate the loss or the acquisition of N-glycosylation sites located near the S-interface. […] Of note, Pigs and dogs, which are not or not effectively infected and have only a few changes in the binding site, exhibit relatively low levels of ACE2 in the respiratory tract. […] However, ACE2 of pangolin exhibit seven changes relative to human ACE2, a similar number of substitutions is present in ACE2 of bats, raccoon, and civet suggesting that SARS-CoV-2 may not especially adapted to ACE2 of any of its putative intermediate hosts. […] Effective binding to the host receptor ACE2 is the first prerequisite for infection of cells and determines the host range. […] We found that ACE2 from species known to support SARS-CoV-2 infection tolerate many amino acid changes indicating that the species barrier might be low. […] An exception are dogs and especially pigs, which, however, revealed relatively low ACE2 expression levels in the respiratory tract.
32404898 Similarly, despite the recognition of angiotensin converting enzyme 2 (ACE2) as the receptor for severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), and the role of ACE2 in lung injury; there are conflicting results with the use of angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) in these patients.
32405071 Angiotensin-converting enzyme-2 (ACE2) may increase due to upregulation in patients using angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB). […] Because renin-angiotensin system blockers increase levels of ACE2, a protein that facilitates coronavirus entry into cells, there is concern that these drugs could increase the risk of developing a severe and fatal form of COVID-19.
32405117 SARS-CoV-2 and SARS-CoV recognize angiotensin-converting enzyme 2 (ACE2) receptor via the receptor-binding domain (RBD). […] The 18F3-recognizing epitopes on RBD did not overlap with the ACE2-binding sites, whereas those recognized by 7B11 were close to the ACE2-binding sites, explaining why 7B11 could, but 18F3 could not, block SARS-CoV or SARS-CoV-2 RBD binding to ACE2 receptor.
32405877 Angiotensin-converting enzyme 2 (ACE2) is a co-receptor for SARS-CoV-2, and studies thus far have not concluded a benefit or risk associated with the use of either ACE-inhibitors or angiotensin receptor antagonists.
32406140 SARS-CoV-2 binds to angiotensin converting enzyme-2 (ACE2) to facilitate infection in humans. […] There is preliminary evidence for ACE2 expression on corneal and conjunctival cells, but most of the other receptors to which coronaviruses bind appear to be found under epithelia of the ocular surface.
32406522 We address the role of ACE2, as a functional receptor for SARS-CoV-2, which also was found in the gastrointestinal tract.
32407491 Two use-case studies were demonstrated, one being on ACE2 protein which is SARS-CoV-2 Spike protein receptor. […] ACE2 binding compounds and 7 antiviral drugs were closely embedded in which two of them have been under clinical trial for COVID-19. iBioProVis and its carefully filtered dataset are available at for public use.
32408547 This enzyme facilitates viral particle entry into host cells, and its inhibition blocks virus fusion with angiotensin-converting enzyme 2 (ACE2).
32409230 Additionally, blocking the receptor, ACE2 via the neutralizing antibodies for viral escape that prevents it from entering into the cells provides another therapeutic regimen.
32409434 Concerns have been raised about the potential for renin-angiotensin system (RAS) inhibitors to upregulate expression of angiotensin-converting enzyme 2 (ACE2) and thus increase susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry. […] Currently, there is no evidence that even if RAS inhibitors increase expression and activity of ACE2, that they would increase the risk of SARS-CoV-2 infection by facilitating greater viral entry or worsen outcomes in patients with COVID-19.
32409501 Although not only ACE inhibitors and angiotensin 2 receptor blockers but also SGLT2 inhibitors, GLP-1 receptor agonists, pioglitazone, and probably insulin seem to increase the number of ACE2 receptors on the cells utilized by SARS-CoV-2 for penetration, no evidence presently exists that shows this might be harmful in terms of acquiring or worsening COVID-19.
32410141 The ACE2 gene is a receptor of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) for COVID-19 (coronavirus disease 2019). […] ACE2 was highly conserved in different species. […] In normal tissues, ACE2 expression distributions were organ-specific, mainly in the kidney, male testis and female breast, and cardiovascular and gastrointestinal systems. […] On the other side, high expression of ACE2 was correlated with increased survival rate in renal and liver cancer, indicating that ACE2 is a prognostic marker in both renal cancer and liver cancers. […] Thus, the ACE2 is a functional receptor for SARS-CoV-2 and has a potential anti-tumor role in cancer. […] Taken together, this study may not only provide potential clues for further medical pathogenesis of COVID-19 and male fertility, but also indicate the clinical significance of the role of the ACE2 gene in cancer.
32410735 Protein-protein binding assays have confirmed that Angiotensin-converting enzyme 2 (ACE2) is more likely to be the cell receptor through which the virus invades the host cell. […] In the present work, we provide an insight into the interaction of the viral spike Receptor Binding Domain (RBD) from different coronavirus isolates with host ACE2 protein. […] By calculating the binding energy score between RBD and ACE2, we highlighted the putative jump in the affinity from a progenitor form of SARS-CoV-2 to the current virus responsible for COVID-19 outbreak. […] We also highlighted the relevance of Q493 and P499 amino acid residues of SARS-CoV-2 RBD for binding to human ACE2 and maintaining the stability of the interface. […] Finally, we studied the impact of eight different variants located at the interaction surface of ACE2, on the complex formation with SARS-CoV-2 RBD.
32412156 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects human cells binding to angiotensin-converting enzyme 2 (ACE2), an enzyme responsible for the cleavage of angiotensin II into angiotensin 1-7, which has vasodilating and anti-inflammatory effects. […] Virus-mediated down-regulation of ACE2 may increase angiotensin II stimulation and contribute to the deleterious hyper-inflammatory reaction of COVID-19. […] On the other hand, ACE2 may be up-regulated in patients with cardiac disease and treated with ACE inhibitors or angiotensin receptor blockers. […] ACE2 up-regulation may increase the susceptibility to COVID-19 but may be also protective vs. angiotensin II-mediated vasoconstriction and inflammatory activation.
32412918 We used the following search terms: “Coronavirus” or “2019-nCoV” or “COVID-19” or “SARS-CoV” or “MERS-CoV” or “Bat SARS-CoV” or “ACE2 receptor”. […] Researchers are presuming the existence of angiotensin-converting enzyme 2 (ACE2) receptor binding in nCoV-2019, as in SARS-CoV.
32412919 It has been reported that women from the Chinese Han population are associated with essential hypertension due to their relation with the 5 SNPs, namely, rs1514283, rs4646155, rs4646176, rs2285666, and rs879922, which belong to the ACE2 gene. […] The level of ACE2 activity was very low in normal healthy younger persons, and was reported to be increased in patients with cardiovascular diseases.
32413300 Viral entry is mediated through viral spike protein and host ACE2 enzyme interaction.
32413319 SARS-CoV-2 spike (S) protein binds angiotensin-converting enzyme 2 (ACE2), and in concert with host proteases, principally transmembrane serine protease 2 (TMPRSS2), promotes cellular entry. […] The cell subsets targeted by SARS-CoV-2 in host tissues and the factors that regulate ACE2 expression remain unknown. […] We identify ACE2 and TMPRSS2 co-expressing cells within lung type II pneumocytes, ileal absorptive enterocytes, and nasal goblet secretory cells. […] Strikingly, we discovered that ACE2 is a human interferon-stimulated gene (ISG) in vitro using airway epithelial cells and extend our findings to in vivo viral infections. […] Our data suggest that SARS-CoV-2 could exploit species-specific interferon-driven upregulation of ACE2, a tissue-protective mediator during lung injury, to enhance infection.
32414646 Recently it was shown that the SARS-CoV-2 spike protein, binds to the human angiotensin I converting enzyme 2 (ACE2). […] Humans are not equal with respect to the expression levels of the cellular ACE2. […] Moreover, ACE2 polymorphisms were recently described in human populations. […] Here we review the most recent evidence that ACE2 expression and/or polymorphism could influence both the susceptibility of people to SARS-CoV-2 infection and the outcome of the COVID-19 disease. […] Further exploration of the relationship between the virus, the peptidase function of ACE2 and the levels of angiotensin II in SARS-CoV-2 infected patients should help to better understand the pathophysiology of the disease and the multi-organ failures observed in severe COVID-19 cases, particularly heart failure.
32414711 The SARS-CoV-2 virus enters the cell via ACE2. […] ACE2 is a component of the renin-angiotensin system (RAS) which has an important counterregulatory effect on the classical ACE-dependent pathway. […] Several antihypertensives increase ACE2 expression or activity, leading to concern that this may facilitate SARS-CoV-2 entry and worsen COVID-19 disease. […] However, ACE2 is protective against lung injury while ANG II (which is catabolised by ACE2) is associated with lung injury both in mice and humans.
32415260 The viral spike protein binds the host receptor angiotensin-converting enzyme 2 (ACE2) via the receptor-binding domain (RBD), and thus is believed to be a major target to block viral entry. […] Here we functionally analyzed the key amino acid residues located within receptor binding motif of RBD that may interact with human ACE2 and available neutralizing antibodies.
32415419 Here, we discuss different modes of action (anti-inflammatory, antioxidant, inhibition of endosomal acidification, suppression of angiotensin-converting enzyme 2 or ACE2 glycosylation, etc.) of HCQ that might be responsible for its possible anti-COVID-19 effect.
32415481 Given the SARS-CoV-2 likely uses the angiotensin-converting enzyme-2 (ACE2) receptors as its host receptor, ACE2-related signaling pathways may play a key role in mediating myocardial injury.
32415494 Scientists hypothesized that drugs such as ibuprofen or renin-angiotensin system (RAS) blockers could exacerbate the novel coronavirus disease COVID-19 by upregulating the angiotensin-converting enzyme 2 (ACE2), which serves as an entry receptor for the coronavirus SARS-CoV-2.
32416074 In contrast, RmYN02 showed low sequence identity (61.3%) to SARS-CoV-2 in the receptor-binding domain (RBD) and might not bind to angiotensin-converting enzyme 2 (ACE2).
32416259 By constant-pH Monte Carlo simulations and the PROCEEDpKa method, we have mapped the electrostatic epitopes for four monoclonal antibodies and the angiotensin-converting enzyme 2 (ACE2) on both SARS-CoV-1 and the new SARS-CoV-2 S receptor binding domain (RBD) proteins. […] We also calculated free energy of interactions and shown that the S RBD proteins from both SARS viruses binds to ACE2 with similar affinities. […] However, the affinity between the S RBD protein from the new SARS-CoV-2 and ACE2 is higher than for any studied antibody previously found complexed with SARS-CoV-1.
32416679 Such machinery encompasses SARS-CoV-2 envelope spike (S) glycoprotein required for host cell entry by binding to the ACE2 receptor, viral RNA-dependent RNA polymerase (RdRp) and 3-chymotrypsin-like main protease (3Clpro/Mpro).
32417709 Hypertensive individuals, usually grouped with other conditions, are treated with drugs to reduce blood pressure mostly through ACEi and ARB, that leads to increased ACE2 expression, used by SARS-CoV-2 for human’s cell entry.
32418199 Angiotensin-converting enzyme-2 (ACE2) has been established as the functional host receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the current devastating worldwide pandemic of coronavirus disease 2019 (COVID-19). […] ACE2 is abundantly expressed in a variety of cells residing in many different human organs. […] In human physiology, ACE2 is a pivotal counter-regulatory enzyme to ACE by the breakdown of angiotensin II, the central player in the renin-angiotensin-aldosterone system (RAAS) and the main substrate of ACE2. […] Many factors have been associated with both altered ACE2 expression and COVID-19 severity and progression, including age, sex, ethnicity, medication and several co-morbidities, such as cardiovascular disease and metabolic syndrome. […] Although ACE2 is widely distributed in various human tissues and many of its determinants have been well recognised, ACE2-expressing organs do not equally participate in COVID-19 pathophysiology, implying that other mechanisms are involved in orchestrating cellular infection resulting in tissue damage. […] Reports of pathologic findings in tissue specimens of COVID-19 patients are rapidly emerging and confirm the established role of ACE2 expression and activity in disease pathogenesis. […] In this review, we describe the role of ACE2 in COVID-19 pathophysiology, including factors influencing ACE2 expression and activity in relation to COVID-19 severity.
32418532 Recently, SARS-CoV-2 [8, 9], the causative agent of COVID-19, has been described to interfere with the RAS [2] by interacting -via its spike (S) glycoprotein- with the metallopeptidase Angiotensin-Converting Enzyme 2 (ACE2) receptor [9, 10] that is expressed at the surface of epithelial cells from blood vessels, lung, kidney (renal tubules), intestine, and heart, as well as on cerebral neurons and immune monocytes/macrophages [11-13]. […] The latter is cleaved by the Angiotensin-Converting Enzyme (ACE) to produce Angiotensin II (i.e. peptide DRVYIHPF), which is the substrate of ACE2 (SARS-CoV-2 receptor) and key player of the RAS. […] When cleaved by ACE2, Angiotensin II gives Angiotensin 1-7 (i.e. peptide DRVYIHP), targeting the vasodilatator proto-oncogene Mas receptor (MasR). […] Angiotensin II can produce Angiotensin A (i.e. peptide ARVYIHPF) via an aspartate decarboxylase, and Alamandine via an additional ACE2 cleavage. […] ACE2 can also cleave Angiotensin I to form Angiotensin 1-9 (i.e. peptide DRVYIHPFH), which targets AT2R. […] Interestingly, it appears that a ‘counter-regulatory’ RAS does exist to modulate system homeostasis; it relies on Angiotensin 1-7, Angiotensin 1-9, Alamandine, Angiotensin A, and Angiotensin IV, which are targeting the MasR, AT2R, MRGD, ACE2 and AT4R vasodilatator receptors, respectively. […] It appears that COVID-19 disorders of SARS-CoV-2-infected humans depend on the RAS over-reacted by the (ACE2-dependent) viral infection and vitamin D deficiency. […] Recombinant ACE2 (under clinical trials) is also considered as a decoy for the recognition and competitive binding to the spike (S) glycoprotein of SARS-CoV-2 [9, 10]. […] The targeted receptors would thus be MasR, AT2R, MRGD, ACE2 and AT4R.
32418550 SARS-CoV-2 and mustard gas inducing oxidative stress, immune system dysregulation, cytokine storm, and overexpression of ACE2 receptor in lungs that act as functional entry receptors for SARS-CoV-2.
32419720 We speculate that male 2D:4D is a negative correlate for expression of the SARS-CoV2 receptor (ACE2).
32419926 Moreover, the well-known SARS-CoV receptor (ACE2) might be a putative receptor for the novel virus as well.
32420049 The virus mainly targets the pulmonary epithelial cells as it’s initial site of infection by letting its surface spike protein interact and bind to the host ACE2 receptor.
32420934 Tobacco smoking seems to cause a dose-dependent upregulation of the angiotensin-converting- enzyme-2 (ACE2), the virus cellular entry receptor, which could explain the higher risk of severe COVID-19 in smokers.
32421102 The ZDOCK protein docking software was applied to dock the S-protein with the human angiotensin ACE2 protein to find out the key amino acids of the binding site. […] Taking ACE2 as the receptor, the molecular docking between the active ingredients and the target protein was studied by AutoDock molecular docking software. […] Through the protein docking between S-protein and ACE2, it is found that Glu329/Gln325 and Gln42/Asp38 in ACE2 play an important role in the binding process of the two. […] The results of molecular docking virtual calculation showed that phillyrin and chlorogenic acid could stably combine with Gln325 and Gln42/Asp38 in ACE2, respectively, which hindered the combination between S- protein and ACE2. […] Phillyrin and chlorogenic acid can effectively prevent the combination of SARS-CoV-2 S-protein and ACE2 at the molecular level.
32421367 The main host receptor of the SARS-CoV-2 is angiotensin converting enzyme 2 (ACE2), a major component of the renin-angiotensin-aldosterone system (RAAS). […] The ACE2 is also involved in testicular male regulation of steroidogenesis, and spermatogenesis. […] As the SARS-CoV-2 may have the potential to infect the testis via ACE2, and adversely affect male reproductive system, it is essential to commence with targeted studies to learn from current pandemic, with the possibility of preemptive intervention depending on findings and the time course of the continued pandemic.
32422146 To extend our work in interleukin (IL)-13 biology to determine if airway epithelial cell expression of two key mediators critical for SARS-CoV-2 infection, angiotensin-converting enzyme 2 (ACE2) and transmembrane protease, serine 2 (TMPRSS2) are modulated by IL-13. […] We determined effects of IL-13 treatment on ACE2 and TMPRSS2 expression ex vivo in primary airway epithelial cells from participants with and without type 2 asthma obtained by bronchoscopy. […] We also examined expression of ACE2 and TMPRSS2 in two datasets containing gene expression data from nasal and airway epithelial cells from children and adults with asthma and allergic rhinitis. […] IL-13 significantly reduced ACE2 and increased TMPRSS2 expression ex vivo in airway epithelial cells. […] In two independent datasets, ACE2 expression was significantly reduced and TMPRSS2 was significantly increased in the nasal and airway epithelial cells in type 2 asthma and allergic rhinitis. […] ACE2 expression was significantly negatively associated with type 2 cytokines while TMPRSS2 expression was significantly positively associated with type 2 cytokines. […] IL-13 modulates ACE2 and TMPRSS2 expression in airway epithelial cells in asthma.
32422280 Angiotensin converting enzyme 2 (ACE2), a component of the renin-angiotensin system (RAS), is the human cell receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. […] ACE2 expression increases on lung alveolar epithelial cells and adipose tissue due to obesity, smoking and air pollution. […] A significant relationship exists between air pollution and SARS-CoV-2 infection, as more severe COVID-19 symptoms occur in smokers; comorbid conditions due to obesity or excess ectopic fat accumulation as underlying risk factors for severe COVID-19 strongly encourage the virus/ACE2 receptor-ligand interaction concept.
32422320 First, angiotensin-converting enzyme 2 (ACE2) activity is lost during SARS-CoV-2 viral entry. […] ACE2 is highly expressed in the lungs and heart and converts Angiotensin II into Angiotensin 1-7. […] Loss of ACE2 upon viral entry may tip the balance towards destructive p38 signaling through Angiotensin II.
32422996 An important stage in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) life cycle is the binding of the spike (S) protein to the angiotensin converting enzyme-2 (ACE2) host cell receptor. […] In addition, the trimer cavity may function as a “bouncing spring” that may facilitate the homotrimer spike protein interactions with the ACE2 receptor.
32423094 Firstly, SARS-CoV-2 has a strong interaction with the human ACE2 receptor, which plays an essential role in cell entry together with transmembrane serine protease 2 (TMPRSS2); it is interesting to note that the ACE2 gene lays on the X-chromosome, thus allowing females to be potentially heterozygous and differently assorted compared to men who are definitely hemizygous. […] Secondly, the higher ACE2 expression rate in females, though controversial, might ascribe them the worst prognosis, in contrast with worldwide epidemiological data. […] Other genes, out from the RAS-pathway, might directly or indirectly impact on the ACE1/ACE2 balance by influencing its main actors (e.g., ABO locus, SRY, SOX3, ADAM17). […] Unexpectedly, the higher levels of ACE2 or ACE1/ACE2 rebalancing might improve the outcome of COVID-19 in both sexes by reducing inflammation, thrombosis, and death.
32423095 The four human population groups of Europeans, Africans, Asians, and Americans had specific and also a common pool of rare variants for the X-linked locus of ACE2 receptor. […] Several specific and common ACE2 variants including S19P, I21T/V, E23K, A25T, K26R, T27A, E35D/K, E37K, Y50F, N51D/S, M62V, N64K, K68E, F72V, E75G, M82I, T92I, Q102P, G220S, H239Q, G326E, E329G, G352V, D355N, H378R, Q388L, P389H, E467K, H505R, R514G/*, and Y515C were of the utmost importance to the viral entry and infection. […] Most interestingly, the analyses revealed that more than half of the variants can exist in males, i.e., as hemizygous. (4) Conclusions: The rare variants of human ACE2 seem to be one of the determinant factors associated with fitness in the battle against SARS viruses. […] The hemizygous viral-entry booster variants of ACE2 describe the higher SARS-CoV-2 mortality rate in males.
32423553 Angiotensin-converting enzyme (ACE) and its homologue, ACE2, have been mostly associated with hypertensive disorder. […] However, recent pandemia of SARS-CoV-2 has put these proteins at the center of attention, as this virus has been shown to exploit ACE2 protein to enter cells.
32425270 BD-368-2 also displayed strong therapeutic and prophylactic efficacy in SARS-CoV-2-infected hACE2-transgenic mice. […] Additionally, the 3.8Å Cryo-EM structure of a neutralizing antibody in complex with the spike-ectodomain trimer revealed the antibody’s epitope overlaps with the ACE2 binding site.
32425701 Here, we show that cigarette smoke causes a dose-dependent upregulation of Angiotensin Converting Enzyme 2 (ACE2), the SARS-CoV-2 receptor, in rodent and human lungs. […] Using single-cell sequencing data, we demonstrate that ACE2 is expressed in a subset of secretory cells in the respiratory tract. […] Chronic smoke exposure triggers the expansion of this cell population and a concomitant increase in ACE2 expression. […] In contrast, quitting smoking decreases the abundance of these secretory cells and reduces ACE2 levels. […] Finally, we demonstrate that ACE2 expression is responsive to inflammatory signaling and can be upregulated by viral infections or interferon treatment. […] Furthermore, our work identifies ACE2 as an interferon-stimulated gene in lung cells, suggesting that SARS-CoV-2 infections could create positive-feedback loops that increase ACE2 levels and facilitate viral dissemination.
32428380 SARS-CoV-2 utilises angiotensin converting enzyme 2 (ACE2) to gain cellular entry. […] We have investigated whether ACE2 bronchial epithelial expression is increased in COPD patients who are overweight compared to those who are not by RNA sequencing. […] We observed increased ACE2 expression in COPD patients who are overweight (mean BMI 29 kg/m2 ) compared to those notoverweight (mean BMI 21 kg/m2 ) (p=0.004). […] Increased ACE2 expression may cause increased SARS-CoV-2 infection of the respiratory tract.
32428864 Angiotensin-converting enzyme 2 (ACE2) is not only an entry receptor of the SARS-CoV-2 virus, the virus that causes COVID-19, but also can protect from lung injury. […] In this view, we highlighted potential approaches to address ACE2-mediated SARS-CoV-2 virus, including 1) delivering an excessive soluble form of ACE2 (recombinant human ACE2: rhACE2) and 2) inhibition of the interaction between SARS-CoV-2 virus and ACE2 by some compounds with competitive effects (morphine and codeine).
32430279 Although, SARS-Cov-2 primarily causes lung infection through binding of ACE2 receptors present on the alveolar epithelial cells, yet it was recently reported that SARS-CoV-2 RNA was found in the faeces of infected patients. […] Interestingly, the intestinal epithelial cells particularly the enterocytes of the small intestine also express ACE2 receptors.
32430459 There is good evidence that ACE2 is a receptor for SARS-CoV-2, and high expression of ACE2 may increase susceptibility to infection. […] We aimed to explore risk factors affecting susceptibility to infection and prioritize drug repositioning candidates, based on Mendelian randomization (MR) studies on ACE2 lung expression. […] We conducted a phenome-wide MR study to prioritize diseases/traits and blood proteins causally linked to ACE2 lung expression in GTEx. […] We also explored drug candidates whose targets overlapped with the top-ranked proteins in MR, as these drugs may alter ACE2 expression and may be clinically relevant. […] The most consistent finding was tentative evidence of an association between diabetes-related traits and increased ACE2 expression. […] Based on one of the largest genome-wide association studies on type 2 diabetes mellitus (T2DM) to date (N = 898,130), T2DM was causally linked to raised ACE2 expression (P = 2.91E-03; MR-IVW). […] Significant associations (at nominal level; P < 0.05) with ACE2 expression were observed across multiple diabetes data sets and analytic methods for T1DM, T2DM, and related traits including early start of insulin. […] Our analysis suggested that diabetes and related traits may increase ACE2 expression, which may influence susceptibility to infection (or more severe infection). […] Proteome-wide MR analyses might help uncover mechanisms underlying ACE2 expression and guide drug repositioning.
32430627 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells following binding with the cell surface ACE2 receptors, thereby leading to coronavirus disease 2019 (COVID-19).
32432483 The first step in SARS-CoV-2 infection is binding of the virus to angiotensin converting enzyme 2 (ACE2) on the airway epithelium. […] The objective was to gain insight into the expression of ACE2 in the human airway epithelium. […] Airway epithelium sampled by fiberoptic bronchoscopy of trachea, large airway epi-thelium (LAE) and small airway epithelium (SAE) of nonsmokers and smokers was analyzed for expression of ACE2 and other coronavirus infection-related genes using microarray, RNA-seq and 10x single cell transcriptome analysis, with associated examination of ACE2-related miRNA. […] (1) ACE2 is expressed similarly in the trachea and LAE with lower expression in the SAE; (2) in the SAE, ACE2 is expressed in basal, intermediate, club, mu-cus and ciliated cells; (3) ACE2 is up-regulated in the SAE by smoking, significantly in males; (4) levels of miR-1246 expression could play a role in ACE2 up-regulation in the SAE of smokers; and (5) ACE2 is expressed in airway epithelium differentiated in vitro on air-liquid interface cultures from primary airway basal stem/progenitor cells; this can be replicated using LAE and SAE immortalized basal cell lines derived from healthy nonsmokers. […] ACE2, the gene encoding the receptor for SARS-CoV-2, is expressed in the human airway epithelium, with variations in expression relevant to the biology of initial steps in SARS-CoV-2 infection.
32432519 We discuss the possible excess risk for COVID-19 infection in the context of the common conditions among shiftworkers, including nurses, doctors, and first responders, among others of high exposure to the contagion, of sleep imbalance and circadian disruption.Abbreviations: ACE2: Angiotensin-converting enzyme 2; APC: Antigen-presenting cells; CCL: Chemokine (C-C motif) ligand; CD+: Adhesion molecule expression; COVID-19: 2019 coronavirus disease; DCs: Dendritic cells; GH: Growth hormone; HPA: Hypothalamic-pituitary-adrenal; HSF: Heat shock factor; HSP70: Heat shock protein 70; HSP90: Heat shock protein 90; IL: Interleukin; INFγ: Interferon-gamma; LT/LB: T/B lymphocytes; MHC: Major histocompatibility complex; NK: Natural killer; RAAS: renin-angiotensin-aldosterone system; SARS: Severe acute respiratory syndrome; SCN: Suprachiasmatic nucleus;SD: Sleep deprivation; SNS: Sympathetic nervous system; Th1/Th2: T helper lymphocytes 1/2; TLR2/TLR4: Toll-like receptor 2/4; TNF-α: Tumor necrosis factor alpha; VEGF: Vascular endothelial growth factor.
32432918 Here we report that estrogen can regulate the expression of ACE2, a key component for SARS-CoV-2 cell entry, in differentiated airway epithelial cells.
32433344 The benefits are associated with the significant increase of intrarenal angiotensin-converting enzyme II (ACE2) expression and blood volume contraction. […] However, the increased ACE2 may be detrimental to patients infected with the coronavirus infection 2019 (COVID-19), which is found to invades cells via the entry receptor of ACE2.
32433465 Following immunization of mice and guinea pigs with INO-4800 we measure antigen-specific T cell responses, functional antibodies which neutralize the SARS-CoV-2 infection and block Spike protein binding to the ACE2 receptor, and biodistribution of SARS-CoV-2 targeting antibodies to the lungs.
32435607 We aim to explore the potential role of angiotensin-converting enzyme 2 (ACE2) in this regard through this literature review. […] As a crucial enzyme of renin-angiotensin-aldosterone system (RAAS), ACE2 not only mediates the virus entry but also affects the pathophysiological process of virus-induced acute lung injury (ALI), as well as other organs’ damage. […] As interaction of COVID-19 virus spike and ACE2 is essential for virus infection, COVID-19-specific vaccine based on spike protein, small molecule compound interrupting their interaction, human monoclonal antibody based on receptor-binding domain, and recombinant human ACE2 protein (rhuACE2) have aroused the interests of researchers. […] Meanwhile, ACE2 could catalyze angiotensin II (Ang II) to form angiotensin 1-7 (Ang 1-7), thus alleviates the harmful effect of Ang II and amplifies the protection effect of Ang1-7. […] ACE inhibitor and angiotensin II receptor blocker (ARB) have been shown to increase the level of expression of ACE2 and could be potential strategies in protecting lungs, heart, and kidneys. […] ACE2 plays a very important role in the pathogenesis and pathophysiology of COVID-19 infection. […] Strategies targeting ACE2 and its ligand, COVID-19 virus spike protein, may provide novel method in the prevention and management of novel coronavirus pneumonia.
32436229 As well as SARS-CoV, SARS CoV-2 uses the ‘Angiotensin Converting Enzyme-2’ (ACE2) as a receptor to enter human cells. […] It was found that ACE2, Angiotensin (1-7) and its MAS receptors are present, over in the lung, also in the testicles, in particular in Leydig and Sertoli cells. […] A second hypothesis is that the binding of the virus to the ACE2 receptor, could cause an excess of ACE2 and give rise to a typical inflammatory response.
32436995 SARS-CoV-2 appears to have neurotropic aspects with neurotoxicity through interaction with ACE2 in the medullary brainstem, causing glutamate toxicity in the rostral ventrolateral medulla (RVLM), increased sympathetic tone, hypertension and pulmonary capillary leakage of fluid into the alveoli, resulting in acute respiratory distress syndrome (ARDS).
32437004 SARS-CoV-2 can cause liver injury through systemic inflammatory response syndrome (SIRS), cytokine storms, ischemia-reperfusion injury, side effects of treatment drugs, and underlying liver disease and can attack liver cells directly via ACE2.
32437244 Angiotensin converting enzyme 2 (ACE2) acts as the receptor for severe acute respiratory syndrome coronavirus (SARS-CoV), which causes COVID-19. […] The expression of ACE2 is influenced by sex hormones; therefore, we discuss in this article that this could be one of the reasons why COVID-19 is more prevalent in men than in women.
32437926 Since SARS-CoV-2 and SARS-CoV have high similarity of their genomic sequences and share the same cellular receptor (ACE2), it is essential to learn the lessons and experiences from the development of SARS-CoV vaccines for the development of SARS-CoV-2 vaccines.
32438383 The virus gains access to the respiratory epithelium through cell surface angiotensin converting enzyme 2 (ACE2). […] Inhaled modified recombinant human ACE2, may bind SARS-CoV-2 and mitigate lung damage.
32441816 Therefore, this study aimed to assess the presence of ACE2/TMPRSS2 expression in salivary glands using publicly available databases. […] The distribution of ACE2 and TMPRSSs family in salivary gland tissue and other tissues was analyzed. […] The GTEx dataset was employed to explore the ACE2 and TMPRSS2 expression in various body organs and salivary glands in a healthy population. […] Transcriptome data analysis showed that ACE2 and TMPRSS2 were expressed in salivary glands. […] The expression levels of ACE2 and TMPRSS2 were marginal without significant differences in different age groups or between men and women.
32442315 Angiotensin-converting enzyme 2 (ACE2) plays an essential role in maintaining the balance of the renin-angiotensin system and also serves as a receptor for the SARS-CoV-2, SARS-CoV, and HCoV-NL63. […] ACE2 is a potential target for many treatment approaches for the SARS-CoV-2. […] With the help of bioinformatics, we have predicted several novel exons of the human ACE2 gene. […] The inclusion of novel exons located in the 5’UTR/intronic region in the mature transcript may remove the critical ACE2 residues responsible for the interaction with the receptor-binding domain (RBD) of SARS-CoV-2, thus preventing their binding and entry into the cell. […] Additionally, inclusion of a novel predicted exons located in the 3’UTR by alternative splicing may remove the C-terminal transmembrane domain of ACE2 and generate soluble ACE2 isoforms. […] Alternative splicing of the ACE2 gene could similarly be modulated using SSOs to exclude critical domains required for the entry of SARS-CoV-2.
32442562 Over the course of hospitalization, Bacteroides dorei, Bacteroides thetaiotaomicron, Bacteroides massiliensis, and Bacteroides ovatus, which downregulate expression of ACE2 in murine gut, correlated inversely with SARS-CoV-2 load in fecal samples from patients.
32445872 The angiotensin-converting enzyme 2 receptor (ACE2) is expressed in epithelial cells of many tissues including the kidney, and has been identified to interact with human pathogenic coronaviruses, including SARS-CoV-2. […] Interestingly, studies in rats have demonstrated that high dietary sodium intake results in down-regulation of the ACE2 expression in kidney tissue. […] We hypothesize that low sodium status makes kidney involvement during the course of COVID-19 infection more likely due to upregulation of membrane bound ACE2 in the kidneys.
32446267 As the angiotensin-converting enzyme 2 (ACE2) facilitates the entry of coronaviruses into target cells, there have been hypotheses that preexisting use of Renin-Angiotensin-Aldosterone System (RAAS) inhibitors may increase the risk of developing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. […] Given the common use of RAAS inhibitors among solid organ transplant recipients, we sought to review the RAAS cascade, the mechanism of SARS-CoV-2 entry, and pertinent data related to the effect of RAAS inhibitors on ACE2 to guide management of solid organ transplant recipients during the COVID-19 pandemic.
32446866 The virus may bind to corneal and conjunctival angiotensin converting enzyme 2 (ACE2) receptors and potentially to the lipophilic periocular skin and superficial tear film with downstream carriage into the nasopharynx and subsequent access to the lungs and gut. […] A combination such as hydroxychloroquine, azithromycin and zinc, all of which have previously been used topically in the eye and which work at least in part by blocking ACE2 receptors, may offer a safe, cost-effective and resource-sparing intervention.
32448098 The present study was designed to elucidate the structural changes, hot spot binding residues and their interactions between the nCoV S-protein RBD and ACE2 receptor through computational approaches. […] The nCoV RBD was found binding to ACE2 receptor with 11 hydrogen bonds and 1 salt bridge. […] The major hot spot amino acids involved in the binding identified by interaction analysis after simulations includes Glu 35, Tyr 83, Asp 38, Lys 31, Glu 37, His 34 amino acid residues of ACE2 receptor and Gln 493, Gln 498, Asn 487, Tyr 505 and Lys 417 residues in nCoV S-protein RBD.
32448590 Notably, in the context of coronavirus disease 2019 (COVID-19), the transcript for angiotensin I converting enzyme 2 (ACE2), a negative regulator of the angiotensin system, was the single most up-regulated gene in HCM (fold-change, 3.53; q-value =1.30×10-23), which was confirmed by qRT-PCR in triplicate (fold change, 3.78; P=5.22×10-4), and Western blot confirmed greater than 5-fold overexpression of ACE2 protein (fold change, 5.34; P=1.66×10-6). […] Importantly, ACE2 was the most up-regulated gene in HCM, indicating perhaps the heart’s compensatory effort to mount an antihypertrophic, antifibrotic response. […] However, given that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses ACE2 for viral entry, this 5-fold increase in ACE2 protein may confer increased risk for COVID-19 manifestations and outcomes in patients with increased ACE2 transcript expression and protein levels in the heart.
32450087 We have therefore explored ACE2 receptor mRNA expression, and co-factors for Sars-CoV-2 infectivity (TMPRSS2 and furin) in bronchial brushes and biopsies from people with asthma and healthy controls, and looked for relationships between asthma severity, Th2- and IL-17 dependent gene signatures, and clinical demographics (age, sex). […] The only significant association was a positive correlation between ACE2 and IL-17-dependent gene expression, and an inverse correlation between ACE2 and Th2-cytokine-dependent gene expression. […] These data suggest that differences in ACE2, TMPRSS2 and furin epithelial and airway gene expression are unlikely to confer enhanced COVID-19 pneumonia risk in patients with asthma across all treatment intensities and severity.
32450165 It is associated with the other organ damage such as cardiovascular risk via an increased level of hypertension through ACE2, gastrointestinal dysfunction, chronic kidney disease, diabetes mellitus, liver dysfunction, lung injury, CNS risk, ocular risks such as chemosis, conjunctivitis, and conjunctival hyperemia, cancer risk, venous thromboembolism, tuberculosis, aging, and cardiovascular dysfunction and reproductive risk.
32452644 The key steps of virus life cycle have been recently clarified, highlighting the role of host type 2 angiotensin converting enzyme (ACE2) and TMPRSS2 serine protease in virus-cell binding and entry, respectively. […] Importantly, major concerns derive from the androgen-dependent tissue-expression of both TMPRSS2 and ACE2, suggesting a differential clinical course of the infection between genders.
32452762 Single cell RNA-seq from 65 studies shows significant overlap between expression of ENaC-α and the viral receptor ACE2 in cell types linked to the cardiovascular-renal-pulmonary pathophysiology of COVID-19.
32453494 The expression of ACE2 and TMPRSS2 in the testis and in the male genital tract allows speculations about a possible testicular involvement during the infection, possibly mediated by local and/or systemic inflammation that might allow a high viral load to overcome the haemato-testicular barrier.
32454512 Further structural studies revealed that CB6 recognizes an epitope that overlaps with angiotensin converting enzyme 2 (ACE2)-binding sites in SARS-CoV-2 receptor binding domain (RBD), thereby interfering with the virus/receptor interactions by both steric hindrance and direct interface-residue competition.
32454513 SARS-CoV-2 entry into the target cells depends on binding between the receptor-binding domain (RBD) of the viral Spike protein and the ACE2 cell receptor2,4-6. […] We identified antibodies with potent anti-SARS-CoV-2 neutralization activity that correlates with their competitive capacity with ACE2 for RBD binding. […] Crystal structure analysis of RBD-bound antibody revealed steric hindrance that inhibits viral engagement with ACE2 and thereby blocks viral entry.
32455539 We found that the receptor and transmembrane protease necessary for SARS-CoV-2 entry into host cells, ACE2 and TMPRSS2, respectively, were upregulated in smoking samples from both lung and oral epithelial tissue. […] We then explored the mechanistic hypothesis that smoking may upregulate ACE2 expression through the upregulation of the androgen pathway. […] ACE2 and TMPRSS2 upregulation were both correlated to androgen pathway enrichment and the specific upregulation of central pathway regulatory genes. […] These data provide a potential model for the increased susceptibility of smoking patients to COVID-19 and encourage further exploration into the androgen and tobacco upregulation of ACE2 to understand the potential clinical ramifications.
32455629 Genes required for SARS-CoV-2 entry into human cells, ACE2 and FURIN, were employed as baits to build genomic-guided molecular maps of upstream regulatory elements, their expression and functions in the human body, and pathophysiologically relevant cell types. […] Repressors and activators of the ACE2 and FURIN genes were identified based on the analyses of gene silencing and overexpression experiments as well as relevant transgenic mouse models. […] Of major concern is the ACE2 and FURIN expression in many human cells and tissues, including immune cells, suggesting that SARS-CoV-2 may infect a broad range of cellular targets in the human body.
32456846 COVID-19 may enhance complications in individuals with diabetes through an imbalance in angiotension-converting enzyme 2 (ACE2) activation pathways leading to an inflammatory response. […] ACE2 imbalance in the pancreas causes acute β-cell dysfunction and a resultant hyperglycemic state.
32457038 SARS-CoV-2 shares extensive structural and functional conservation with SARS-CoV-1 including engagement of the same host cell receptor (ACE2) localized in cholesterol-rich microdomains.
32458193 In addition, SARS-CoV-2 is structurally similar to SARS-CoV, and both bind to the angiotensin-converting enzyme 2 (ACE2) receptor to enter human cells. […] Thus, cells expressing ACE2, such as neurons and glial cells may act as targets and are thus vulnerable to SARS-CoV-2 infection.
32458206 An effective prophylactic medication to prevent viral entry has to contain, at least, either a protease inhibitor or a competitive virus ACE2-binding inhibitor.
32459372 These drugs are known to induce an increased expression of Angiotensin Converting Enzyme 2 (ACE2). […] ACE2 acts as receptor for the novel SARS-Coronavirus-2 (SARS-CoV-2) which raising the important issue of possible detrimental effects that RAS blockers could exert on the natural history and pathogenesis of the COronaVIrus Disease 19 (COVID-19) and associated excessive inflammation, myocarditis, and cardiac arrhythmias.
32462267 As angiotensin-converting enzyme 2 (ACE2) is regarded as the viral receptor for cell entry and as the Coronavirus is downregulating this enzyme, which provides cardiovascular and pulmonary protection, there is ongoing discussions on whether treatment with cardiovascular drugs, which upregulate the viral receptor ACE2 should be modified.
32462701 At the time of writing, in vivo studies of SARS-CoV-2 infection have been described using macaques, cats, ferrets, hamsters, and transgenic mice expressing human angiotensin I converting enzyme 2 (ACE2).
32462996 Among the studied compounds, we found that dithymoquinone (DTQ), with binding affinity of -8.6 kcal/mol compared to a positive control (chloroquine, -7.2 kcal/mol) , has the high potential of binding at SARS-CoV-2:ACE2 interface and thus could be predicted a plausible inhibitor to disrupt viral-host interactions.
32463239 In spite of the high sequence identity of SARS-CoV-2 with its closely related SARS-CoV emerged in 2002, the atomic-level determinants underlining the molecular recognition of SARS-CoV-2 to the angiotensin-converting enzyme 2 (ACE2) receptor and, thus, the rapid virus spread into human body, remain unresolved. […] Here, multi-µs-long molecular dynamics simulations enabled us to unprecedentedly dissect the key molecular traits liable of the higher affinity/specificity of SARS-CoV-2 towards ACE2, as compared to SARS-CoV, supplying a minute per-residue contact map underlining its stunningly high infectivity.
32463365 A hypothesis-free profiling of ACE2 suggests tongue keratinocytes, olfactory epithelial cells, airway club cells and respiratory ciliated cells as potential reservoirs of the SARS-CoV-2 receptor. […] We find the gut as the putative hotspot of COVID-19, where a maturation correlated transcriptional signature is shared in small intestine enterocytes among coronavirus receptors(ACE2, DPP4, ANPEP).
32464367 Cerebrovascular disease, in particular large-vessel ischemic strokes, and less frequently cerebral venous thrombosis, intracerebral hemorrhage and subarachnoid hemorrhage, usually occur as part of a thrombotic state induced by viral attachment to ACE2 receptors in endothelium causing widespread endotheliitis, coagulopathy, arterial and venous thromboses.
32464637 Because SARS-CoV-2 enters the cell by binding to angiotensin-converting enzyme 2 (ACE2), targeting ACE2 to prevent such binding seems an obvious strategy to combat infection. […] However, ACE2 performs its functions outside the cell and was found to enter the cell only by angiotensin II type 1 receptor (AT1R)-induced endocytosis, after which ACE2 is destroyed. […] This means that preventing uptake of ACE2 into the cell by blocking AT1R would be a more logical approach to limit entry of SARS-CoV-2 into the cell. […] Since ACE2 plays an important protective role in maintaining key biological processes, treatments should not disrupt the functional capacity of ACE2, to counterbalance the negative effects of the infection. […] AT1R antagonists counterbalance the negative consequences of angiotesnin II and, in addition, they might even be involved in preventing the cellular uptake of the virus without interfering with ACE2 function.
32469114 ACE-related carboxypeptidase (ACE2), a monocarboxypeptidase that had been discovered 20 years ago, is one of the catalytically most potent enzymes known to degrade Ang II to Ang-(1-7), a peptide that is increasingly accepted to have organ -protective properties that oppose and counterbalance those of Ang II. […] In addition to its role as a RAS enzyme ACE2 is the main receptor for SARS-CoV-2. […] In this review, we discuss various strategies that have been used to achieve amplification of ACE2 activity including the potential therapeutic potential of soluble recombinant ACE2 protein and novel shorter ACE2 variants.
32469255 Angiotensin-converting enzyme 2 (ACE2), belonging to the RAS family, has received much attention during this COVID-19 pandemic, owing to the fact that SARS-CoV-2 uses ACE2 as a receptor for cellular entry.
32470767 We speculate that male 2D:4D is a negative correlate for expression of the SARS-CoV2 receptor (ACE2).
32471115 The RAS is a complicated network of G-protein coupled receptors (GPCRs) (i.e., AT1R, AT2R, MASR, and MRGD) orchestrating the effects of several hormones (i.e., angiotensin II, angiotensin (1-7), and alamandine) produced by protease-based transmembrane receptors (ACE1 and ACE2).
32471251 Vitamin D in particular may perturb viral cellular infection via interacting with cell entry receptors (angiotensin converting enzyme 2), ACE2.
32472991 Furthermore, we highlight the relationship between the virus, enzyme ACE2 and ACE inhibitors.
32475223 The virus exerts its pathogenic activity through by mechanism and gains the entry via spike proteins (S) and Angiotensin-Converting Enzyme 2 (ACE2) receptor proteins on host cells. […] The present work is an effort for a computational target to block the residual binding protein (RBP) on spike proteins (S), Angiotensin-Converting Enzyme 2 (ACE2) receptor proteins by probiotics namely Plantaricin BN, Plantaricin JLA-9, Plantaricin W, Plantaricin D along with RNA-dependent RNA polymerase (RdRp). […] The binding energies for Plantaricin W were -14.64, -11.1 and -12.68 for polymerase, RBD and ACE2 respectively comparatively very high with other compounds. […] Molecular dynamics studies further strengthen stability of the complexes of plantaricin w and SARS-CoV-2 RdRp enzyme, RBD of spike protein, and human ACE2 receptor. […] The present study present multi-way options either by blocking RBD on S proteins or interaction of S protein with ACE2 receptor proteins or inhibiting RdRp to counter any effect of COVID-19 by Plantaricin molecules paving a way that can be useful in the treatment of COVID-19 until some better option will be available.Communicated by Ramaswamy H.
32476472 SARS-CoV-2 binds to ACE2 receptors and entries into the cell through the fusion of its membrane with that of the cell. […] The loss of ACE2 receptor activity from the external site of the membrane will lead to less angiotensin II inactivation and less generation of antiotensin1-7. […] According to this line of thinking, some therapeutic approaches including recombinant ACE2, exogenous angiotensin1-7 and angiotensin receptor blockers appear particularly promising and are being actively tested.
32478523 Some of these studies showed that the mutations in the SARS-CoV spike (S) protein might be responsible for its higher affinity to the ACE2 human cell receptor. […] In this work, we used molecular dynamics simulations and Monte Carlo sampling to compare the binding affinities of the S proteins of SARS-CoV and SARS-CoV-2 to the ACE2. […] Our results show that the protein surface of the ACE2 at the receptor binding domain (RBD) exhibits negative electrostatic potential, while a positive potential is observed for the S proteins of SARS-CoV/SARS-CoV-2. […] The major contributions to the electrostatic binding energies result from the salt bridges forming between R426 and ACE-2-E329 in the case of SARS-CoV and K417 and ACE2-D30 in the SARS-CoV-2.
32482249 To describe detection of severe acute respiratory syndrome (SARS)-coronavirus 2 (CoV-2) in seminal fluid of patients recovering from coronavirus disease 2019 (COVID-19) and to describe the expression profile of angiotensin-converting enzyme 2 (ACE2) and Transmembrane Serine Protease 2 (TMPRSS2) within the testicle. […] Expression patterns of ACE2 and TMPRSS2 in the human testis are explored through previously published single-cell transcriptome datasets. […] Single-cell transcriptome analysis demonstrates sparse expression of ACE2 and TMPRSS2, with almost no overlapping gene expression. […] Angiotensin-converting enzyme 2-mediated viral entry of SARS-CoV-2 into target host cells is unlikely to occur within the human testicle based on ACE2 and TMPRSS2 expression.
32482250 Coronavirus binding to cells involves the S1 domain of the spike protein to receptors present in reproductive tissues, including angiotensin-converting enzyme-2 (ACE2), CD26, Ezrin, and cyclophilins. […] Gonadotropin-dependent expression of ACE2 was found in human ovaries, but it is unclear whether SARS-Coronavirus 2 (CoV-2) adversely affects female gametogenesis.
32485082 The SARS-CoV-2 virus binds to the angiotensin-converting enzyme 2 (ACE2) receptor for cell entry. […] It has been suggested that angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB), which are commonly used in patients with hypertension or diabetes and may raise tissue ACE2 levels, could increase the risk of severe COVID-19 infection.
32485101 Also, Ang II is considered as the products of SARS-CoV-2-attacking target, angiotensin-converting enzyme 2 (ACE2).
32485164 Human angiotensin-converting enzyme II (ACE2) has been identified as a functional receptor for SARS-CoV-2. […] In this study, we generated a mouse model expressing human ACE2 (hACE2) by using CRISPR/Cas9 knockin technology. […] In comparison with wild-type C57BL/6 mice, both young and aged hACE2 mice sustained high viral loads in lung, trachea, and brain upon intranasal infection. […] Although fatalities were not observed, interstitial pneumonia and elevated cytokines were seen in SARS-CoV-2 infected-aged hACE2 mice. […] Interestingly, intragastric inoculation of SARS-CoV-2 was seen to cause productive infection and lead to pulmonary pathological changes in hACE2 mice.
32486188 SARS-CoV-2 enters cells via ACE2 receptors which are abundant throughout the respiratory tract.
32486196 Although the pathophysiology of the SARS-CoV-2 virus affecting the cerebrovascular system has not been elucidated yet, researchers have identified several pathogenic mechanisms, including a role for the ACE2 receptor.
32487714 Like its predecessors, SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), COVID-19 binds to angiotension converting enzyme 2 (ACE2) receptors to facilitate tissue invasion, and potentially gain entry into the nervous system.1 This single-stranded RNA virus shares 75-80% identical genome sequence with MERS-CoV and SARS-CoV, but has increased virulence, persistence, and lethality.2 Amid catastrophic human suffering, severe neurological complications of COVID-19 have been identified; yet, subtle neurological manifestations have likely been under-reported.
32491073 COVID-19 acts through the angiotensin-converting enzyme 2 (ACE2) receptor.
32491829 It infects epithelial cells expressing angiotensin converting enzyme 2 (ACE2) receptor, which is crucial for viral entry.
32491949 Specifically, decreased expression of proteins, including angiotensin-converting enzyme 2 (ACE2) and Transmembrane Serine Protease 2 (TMPRSS2) in the airway epithelium in children may prevent viral entry.
32492193 Human organs known for Angiotensin-Converting Enzyme 2 (ACE2) expression including the gastrointestinal tract, kidneys, heart, adrenals, brain, and testicles are examples of extra-pulmonary tissues with confirmed invasion by SARS-CoV-2.
32492195 Hussain et al.1 identified 17 natural coding variants for human angiotensin-converting enzyme 2 (ACE2) that were found at important positions for binding of ACE2 with SARS-CoV-2 spike protein1 . […] They suggested that positive prognosis of COVID-19 may be due to the existence of ACE2 variants like rs73635825 and rs143936283 in some individuals, and to screen frequencies of candidate alleles in different populations to predict the prognosis of COVID-191 . […] We contributed with further data for these 17 ACE2 variants using other function prediction tools. […] Moreover, we searched for the minor allele frequency (MAF) for these ACE2 variants as reported in different populations and debated regarding their use in population genetic studies.
32492203 Genetic confirmation of the hypotheses regarding gene expression and mutation pattern of target genes, including angiotensin-converting enzyme-2 (ACE2), transmembrane serine protease 2 (TMPRSS2), basigin (CD147/BSG) and paired basic amino acid cleaving enzyme (FURIN/PCSK3), as well as correlation analysis, was done in relation to lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) using in silico analysis. […] Not only were gene expression and mutation patterns detected, but also there were correlation and survival analysis between ACE2 and other target genes expression levels. […] The total genetic anomaly carrying rate of target genes, including ACE2, TMPRSS2, CD147/BSG, and FURIN/PCSK3, was determined as 8.1% and 21 mutations were detected, with 7 of these mutations having pathogenic features. p.H34N on the RBD binding residues for SARS-CoV-2 was determined in our LUAD patient group. […] According to gene expression analysis results, though the TMPRSS2 level was statistically significantly decreased in the LUSC patient group compared to healthy control, the ACE2 level was determined to be high in LUAD and LUSC groups.
32492292 The spike glycoprotein on the virion surface docking onto the angiotensin-converting enzyme (ACE) 2 dimer is an essential step in the process of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in human cells-involves downregulation of ACE2 expression with systemic renin-angiotensin system (RAS) imbalance and promotion of multi-organ damage. […] In general, the RAS induces vasoconstriction, hypertension, inflammation, fibrosis, and proliferation via the ACE/Ang II/Ang II type 1 receptor (AT1R) axis and induces the opposite effects via the ACE2/Ang (1-7)/Mas axis. […] SARS-CoV-2 induces the ACE2 internalization and shedding, leading to the inactivation of the ACE2/Ang (1-7)/Mas axis. […] In brief, the first hit originates from chronic inflammation activating the ACE/Ang II/AT1R axis, and the second originates from the COVID-19 infection inactivating the ACE2/Ang (1-7)/Mas axis.
32493030 The devastating third phase is in the gas exchange units of the lung, where ACE2 expressing alveolar type II cells and perhaps type I cells are infected.
32493627 The S1 subunit of S protein facilitates ACE2 mediated virus attachment while S2 subunit promotes membrane fusion. […] The presence of glutamine, asparagine, leucine, phenylalanine and serine amino acids in SARS-CoV-2 enhances ACE2 binding.
32495299 SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) binds to the angiotensin-converting enzyme 2 (ACE2), a ubiquitous trans-membrane carboxypeptidase, to enter the cells. […] Preclinical studies have reported that angiotensin receptor blockers (ARBs) and ACE inhibitors might increase ACE2 expression in several cell types. […] Other pharmacological agents are thought to increase ACE2 expression, including statins and proliferator-activated receptor gamma (PPAR-γ) agonists. […] Besides ACE2, other unknown co-factors might be involved in cell infection. […] It has been recently observed that dipeptidyl peptidase-4 (DPP4), the receptor for MERS-CoV (Middle East respiratory syndrome-related coronavirus) and ACE2 have similar expression profiles in the lung.
32496364 Animal data and human studies have shown that angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) increase the expression of ACE2. […] ACE2 is an enzyme found in the heart, kidney, gastrointestinal tract, and lung and is a coreceptor for severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV2), the virus responsible for COVID-19. […] Therefore, one can speculate that discontinuing ACE inhibitor or ARB therapy may lead to decreased ACE2 expression, thereby attenuating the infectivity of SARS-CoV-2, and mitigating the disease progression of COVID-19. […] However, several studies have also shown that ACE2 exhibits reno- and cardioprotection and preserves lung function in acute respiratory distress syndrome, which would favor ACE inhibitor or ARB therapy.
32496587 We performed RNA sequencing and explored available RNA-Seq databases to study gene expression and co-expression of ACE2, CD147 (BSG), CD26 (DPP4) and their direct and indirect molecular partners in primary human bronchial epithelial cells, bronchial and skin biopsies, bronchoalveolar lavage fluid, whole blood, peripheral blood mononuclear cells (PBMCs), monocytes, neutrophils, DCs, NK cells, ILC1, ILC2, ILC3, CD4+ and CD8+ T cells, B cells and plasmablasts. […] ACE2 and TMPRSS2 were coexpressed at the epithelial sites of the lung and skin, whereas CD147 (BSG), cyclophilins (PPIA and PPIB), CD26 (DPP4) and related molecules were expressed in both, epithelium and in immune cells. […] Asthma, COPD, hypertension, smoking, obesity, and male gender status generally led to the higher expression of ACE2- and CD147-related genes in the bronchial biopsy, BAL or blood. […] Interestingly, we also observed higher expression of ACE2- and CD147-related genes in the lesional skin of patients with atopic dermatitis.
32497257 In the attempt to understand how the virus spreads and how to pharmacologically abolish it, it was highlighted that SARS-CoV-2 infects human cells by means of angiotensin converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2) and SARS-CoV-2 main protease (Mpro ). […] Once bound to its receptor ACE2, the other two proteases, in concert with the receptor-mediated signaling, allow virus replication and spread throughout the body. […] Our attention has been focused on the role of ACE2 in that its blockade by the virus increases Bradykinin and its metabolites, well known to facilitate inflammation in the lung (responsible for cough and fever), facilitate both the coagulation and complement system, three mechanisms that are typical of angioedema, cardiovascular dysfunction and sepsis, pathologies which symptoms occur in COVID-19 patients.
32497323 The spike (S) proteins of SARS-CoV-1 and SARS-CoV-2 may use the same host cellular receptor, angiotensin-converting enzyme 2 (ACE2), for entering into host cells. […] The affinity between ACE2 and the SARS-CoV-2 S protein is much higher than that of ACE2 binding to the SARS-CoV S protein, explaining why SARS-CoV-2 seems to be more readily transmitted from the human to human. […] Here, we report that ACE2 can be significantly upregulated after infection of various viruses, including SARS-CoV-1 and SARS-CoV-2, or by the stimulation with inflammatory cytokines such as interferons. […] We propose that SARS-CoV-2 may positively induce its cellular entry receptor, ACE2, to accelerate its replication and spread; high inflammatory cytokine levels increase ACE2 expression and act as high-risk factors for developing COVID-19, and the infection of other viruses may increase the risk of SARS-CoV-2 infection. […] Therefore, drugs targeting ACE2 may be developed for the future emerging infectious diseases caused by this cluster of coronaviruses.
32498696 Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the pathogen of COVID-19, infects the human body using angiotensin-converting enzyme 2 (ACE2) as a receptor identical to the severe acute respiratory syndrome (SARS) pandemic that occurred in 2002-2003. […] SARS-CoV-2 has a higher binding affinity to human ACE2 than to that of other species. […] Here, we review transgenic mice that express human ACE2 in the airway and other epithelia and have shown to develop a rapidly lethal infection after intranasal inoculation with SARS-CoV, the pathogen of SARS. […] This literature review aims to present the importance of utilizing the human ACE2 transgenic mouse model to better understand the pathogenesis of COVID-19 and develop both therapeutics and vaccines.
32499236 The initial mechanism for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is the binding of the virus to the membrane-bound form of ACE2, which is mainly expressed in the lung. […] Since the heart and the vessels also express ACE2, they both could become targets of the virus.
32499909 Among the many possible areas of research, it might be important to understand diet and angiotensin-converting enzyme-2 (ACE2) levels in populations with different COVID-19 death rates since dietary interventions may be of great benefit.
32499983 Upon inoculation, the surface enzyme angiotensin-converting enzyme 2 (ACE2) acts as a receptor protein for viral entry.
32500793 One of the human membrane proteins known to be docked by the virus is angiotensin-converting enzyme 2 (ACE2), proposed to be responsible for viral entry in target cells. […] Recently, the 3D structure of ACE2 has been obtained, showing its physical interaction with B0AT1 (SLC6A19), a plasma membrane transporter involved in the trafficking of amino acids in cells. […] The receptor targeted by SARS-CoV-2 is a supercomplex formed by a dimer of ACE2-B0AT1, in which ACE2 binds the viral protein and B0AT1 stabilizes the heterodimer.
32501190 COVID-19 utilizes the angiotensin-converting enzyme-2 (ACE2) pathway as a means of infection. […] Demographic and clinical comorbidities associated with the severity of infection suggest that possible variants known to influence the renin-angiotensin-aldosterone system pathway (particularly those that influence ACE2) may contribute to the heterogenous infection response. […] ACE2 and angiotensin(1-7) (the product of ACE2) seem to have a protective effect on the pulmonary and cardiac systems. […] Hypertension medication modulation, may alter ACE2 and angiotensin(1-7), particularly in variants that have been shown to influence renin-angiotensin-aldosterone system function, which could be clinically useful in patients with COVID-19.
32501810 Hence, we searched for possible genetic components of COVID-19 severity among Italians by looking at expression levels and variants in ACE2 and TMPRSS2 genes, crucial for viral infection.Exome and SNP-array data from a large Italian cohort were used to compare the rare-variants burden and polymorphisms frequency with Europeans and East Asians. […] Moreover, we looked into gene expression databases to check for sex-unbalanced expression.While we found no significant evidence that ACE2 is associated with disease severity/sex bias, TMPRSS2 levels and genetic variants proved to be possible candidate disease modulators, prompting for rapid experimental validations on large patient cohorts.
32501876 This coronavirus mainly spreads through the respiratory tract and enters cells through angiotensin-converting enzyme 2 (ACE2).
32502616 The co-expression of ACE2 receptor and entry protease TMPRSS2 was detected in the human adult conjunctival, limbal and corneal epithelium, but not in the embryonic and fetal ocular surface up to 21 post conception weeks. […] These expression patterns were corroborated by the single cell ATAC-Seq data, which revealed a permissive chromatin in ACE2 and TMPRSS2 loci in the adult conjunctival, limbal and corneal epithelium. […] Co-expression of ACE2 and TMPRSS2 was strongly detected in the superficial limbal, corneal and conjunctival epithelium, implicating these as target entry cells for SARS-CoV-2 in the ocular surface. […] Strikingly, we also identified the key pro-inflammatory signals TNF, NFKβ and IFNG as upstream regulators of the transcriptional profile of ACE2+TMPRSS2+ cells in the superficial conjunctival epithelium, suggesting that SARS-CoV-2 may utilise inflammatory driven upregulation of ACE2 and TMPRSS2 expression to enhance infection in ocular surface. […] Together our data indicate that the human ocular surface epithelium provides an additional entry portal for SARS-CoV-2, which may exploit inflammatory driven upregulation of ACE2 and TMPRSS2 entry factors to enhance infection.
32502733 Among the 26 variations detected in S, 12 variations were located at the N-terminal domain (NTD) and 6 variations at the receptor-binding domain (RBD) which might alter the interaction of S protein with the host receptor angiotensin-converting enzyme 2 (ACE2).
32502882 Angiotensin-converting enzyme-2 (ACE2) expression may increase due to upregulation in patients using angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs). […] Because renin-angiotensin system blockers increase levels of ACE2, a protein that facilitates coronavirus entry into cells, there is concern that these drugs could increase the risk of developing a severe and fatal form of COVID-19.
32503822 The mechanism for SARS-CoV-2 infection is the binding of the virus spike protein to the membrane-bound form of angiotensin-converting enzyme 2 (ACE2) and internalization of the complex by the host cell.
32503918 Molecular dynamics and free energy simulations have been carried out to elucidate the structural origin of differential protein-protein interactions between the common receptor protein angiotensin converting enzyme 2 (ACE2) and the receptor binding domains of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [A.
32504450 Human angiotensin-converting enzyme 2 (ACE2) widely expressing in arterial and venous endothelial cells and arterial smooth muscle cells has been identified as a functional receptor for SARS-CoV-2. […] Dysfunction of ACE2 leads to abnormal activation of the renin-angiotensin system and a systemic endotheliitis that may relate to abnormal coagulation and sepsis.
32504757 ACE2 plays an important physiological role, practically in all the organs and systems. […] Also, ACE2 exerts protective functions in various models of pathologies with acute and chronic inflammation. […] While ACE2 downregulation by SARS-CoV-2 spike protein leads to an overactivation of Angiotensin (Ang) II/AT1R axis and the deleterious effects of Ang II may explain the multiorgan dysfunction seen in patients.
32504925 SARS-CoV-2 enter into the host cells using the angiotensin-converting enzyme 2 (ACE2) as receptor, like its ancestor SARS-CoV. […] ACE2 is then downregulated in lung tissues with augmented serum levels of ACE2 in SARS-CoV-2 patients. […] Interestingly, ACE2+ organs reveal the symptomatic repercussions, which are signals of the infection such as dry cough, shortness of breath, heart failure, liver and kidney damage, anosmia or hyposmia, and diarrhea. […] ACE2 exerts a chief role in the renin-angiotensin system (RAS) by converting angiotensin II to angiotensin-(1-7) that activates Mas receptor, inhibits ACE1, and modulates bradykinin (BK) receptor sensitivity, especially the BK type 2 receptor (BKB2R). […] ACE2 also hydrolizes des-Arg9-bradykinin (DABK), an active BK metabolite, agonist at BK type 1 receptors (BKB1R), which is upregulated by inflammation. […] In this opinion article, we conjecture a dialogue by the figure of Sérgio Ferreira which brought together basic science of classical pharmacology and clinical repercussions in COVID-19, then we propose that in the course of SARS-CoV-2 infection: i) downregulation of ACE2 impairs the angiotensin II and DABK inactivation; ii) BK and its metabolite DABK seems to be in elevated levels in tissues by interferences in kallikrein/kinin system; iii) BK1 receptor contributes to the outbreak and maintenance of the inflammatory response; iv) kallikrein/kinin system crosstalks to RAS and coagulation system, linking inflammation to thrombosis and organ injury.
32505821 PDL might prevent the entrance of SARS-CoV-2 entry into cells by blocking the angiotensin-converting enzyme 2 (ACE2).
32506195 Virus binds to the cell surface receptor ACE2; indeed, recent evidences suggested that SARS-CoV-2 may be using as co-receptor, when entering the cells, the same one used by MERS-Co-V, namely the DPP4/CD26 receptor. […] The aforementioned observation underlined that mechanism of cell entry is supposedly similar among different coronavirus, that the co-expression of ACE2 and DPP4/CD26 could identify those cells targeted by different human coronaviruses and that clinical complications may be similar.
32506743 SARS-CoV-2 is a novel RNA virus that infects cells expressing the angiotensin-converting enzyme (ACE2) receptor and is associated with an acute respiratory disease named COVID-19. […] It has been hypothesized that ACE2 expression can be increased by Ibuprofen leading to a higher risk for severe COVID-19 (1).
32507883 After transmembrane angiotensin-converting enzyme 2 (ACE2) has been found to be SARS-CoV-2 receptor, we hypothesized an immune-hematological mechanism for Covid-19 based on renin-angiotensin system (RAS) imbalance to explain clinical, laboratory and imaging findings on disease course. […] We believe that exaggerated activation of ACE/Angiotensin II (Ang II)/Angiotensin Type 1 (AT1) receptor RAS axis in line with reduction of ACE2/Angiotensin-(1-7)/Mas receptor may exert a pivotal role in the pathogenesis of Covid-19.
32508311 Early reports have confirmed that transmembrane serine protease 2 (TMPRSS2) and angiotensin converting enzyme 2 (ACE2) are critical targets of SARS-CoV-2 that facilitate viral entry into host cells. […] TMPRSS2 and ACE2 are expressed in multiple human tissues beyond the lung including the testes where predisposition to SARS-CoV-2 infection may exist. […] In this review, we highlight the growing evidence in support of androgen regulation of TMPRSS2 and ACE2 and the potential clinical implications of using androgen suppression to downregulate TMPRSS2 to target SARS-CoV-2. […] We also discuss the future directions and controversies that need to be addressed in order to establish the viability of targeting TMPRSS2 and/or ACE2 through androgen signaling regulation for COVID-19 treatment, particularly its relevance in the context of prostate cancer management.
32510598 Recent studies have found that the pathogen of COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), shares the same cell receptor angiotensin converting enzyme II (ACE2) as SARS-CoV. […] Here, we performed an unbiased evaluation of cell-type-specific expression of ACE2 in healthy and fibrotic lungs, as well as in normal and failed adult human hearts, using published single-cell RNA-seq data. […] We found that ACE2 expression in fibrotic lungs mainly locates in arterial vascular cells, which might provide a route for bloodstream spreading of SARS-CoV-2. […] Failed human hearts have a higher percentage of ACE2-expressing cardiomyocytes, and SARS-CoV-2 might attack cardiomyocytes through the bloodstream in patients with heart failure. […] Moreover, ACE2 was highly expressed in cells infected by respiratory syncytial virus or Middle East respiratory syndrome coronavirus and in mice treated by lipopolysaccharide.
32510973 SARS-CoV-2 may manipulate mitochondrial function indirectly, first by ACE2 regulation of mitochondrial function, and once it enters the host cell, ORFS such as ORF-9b can directly manipulate mitochondrial function to evade host cell immunity and facilitate virus replication and COVID-19 disease. […] We argue that a decline in ACE2 function in aged individuals, coupled with the age-associated decline in mitochondrial functions resulting in chronic metabolic disorders like diabetes or cancer, may make the host more vulnerable to infection and health complications to mortality.
32510978 Notably, the disease course is worse in individuals with preexisting comorbidities that involve endothelial dysfunction and may be linked to elevated ACE2 (angiotensin-converting enzyme 2) expression, such as diabetes mellitus, hypertension, and cardiovascular disease.
32512122 The plausible mechanisms of myocardial injury include, 1) hyperinflammation and cytokine storm mediated through pathologic T-cells and monocytes leading to myocarditis, 2) respiratory failure and hypoxemia resulting in damage to cardiac myocytes, 3) down regulation of ACE2 expression and subsequent protective signaling pathways in cardiac myocytes, 4) hypercoagulability and development of coronary microvascular thrombosis, 5) diffuse endothelial injury and ‘endotheliitis’ in several organs including heart, and, 6) inflammation and/or stress causing coronary plaque rupture or supply-demand mismatch leading to myocardial ischemia/infarction.
32512673 The pathogenesis of COVID-19 starts with the bonding of the virus to ACE2 receptors expressed in many tissues, and the triggered excessive immune response plays a critical role in the course of the disease.
32513532 Recent studies have reported that COVID-19 has angiotensin-converting enzyme 2 (ACE2) as a functional receptor, which may lead to the development of severe cerebrovascular diseases (CVD), including strokes, in patients with risk factors for CVD such as diabetes and smoking. […] Here, we observed ACE2 expression in the brain of rat middle cerebral artery occlusion (MCAO) model and evaluated the effects of cigarette smoke extract (CSE) and diabetes on ACE2 expression in vessels. […] We showed that the levels of ACE2 expression was increased in the cortex penumbra after ischemic injuries. […] CSE treatment significantly elevated ACE2 expression in human brain vessels. […] We found that ACE2 expression was upregulated in primary cultured human blood vessels with diabetes compared to healthy controls. […] This study demonstrates that ACE2 expression is increased in ischemic brains and vessels exposed to diabetes or smoking, makes them vulnerable to COVID-19 infection.
32514935 A number of studies, mainly in animals and not involving the lungs, have indicated that these drugs can increase expression of angiotensin-converting enzyme 2 (ACE2). […] ACE2 is the cell entry receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) that is currently battering the globe.
32515982 The cell entry of SARS-CoV-2 depends on two host proteins angiotensin-converting enzyme 2 (ACE2) and TMPRSS2. […] It is suggested that H2S may block SARS-CoV-2 entry into host cells by interfering with ACE2 and TMPRSS2, inhibit SARS-CoV-2 replication by attenuating virus assembly/release, and protect SARS-CoV-2-induced lung damage by suppressing immune response and inflammation development.
32519842 In this case, nanomaterials could be used to deliver drugs to the pulmonary system to inhibit interaction between angiotensin-converting enzyme 2 (ACE2) receptors and viral S protein.
32520981 The recent emergence of SARS-CoV-2 is responsible for the current pandemic of COVID-19, which uses the human membrane protein ACE2 as a gateway to host-cell infection. […] We performed a comparative genomic analysis of 70 ACE2 placental mammal orthologues to identify variations and contribute to the understanding of evolutionary dynamics behind this successful adaptation to infect humans. […] Our results reveal that 4% of the ACE2 sites are under positive selection, all located in the catalytic domain, suggesting possibly taxon-specific adaptations related to the ACE2 function, such as cardiovascular physiology. […] Considering all variable sites, we selected 30 of them located at the critical ACE2 binding sites to the SARS-CoV-like viruses for analysis in more detail. […] Our results reveal a relatively high diversity of ACE2 between placental mammal species, while showing no polymorphism within human populations, at least considering the 30 inter-species variable sites.
32522067 In this short perspective, we discuss the roles of CQ/HCQ in the treatment of COVID-19 patients and propose new ways of possible treatment for SARS-CoV-2 infection based on the molecules that selectivity target autophagy.Abbreviation: ACE2: angiotensin I converting enzyme 2; CoV: coronavirus; CQ: chloroquine; ER: endoplasmic reticulum; HCQ: hydroxychloroquine; MERS-CoV: Middle East respiratory syndrome coronavirus; SARS-CoV: severe acute respiratory syndrome coronavirus; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2.
32522207 Although the amino acid sequences of the S-glycoprotein were found to be different between the various HCoV, the structures showed high similarity, but the best 3D structural overlap shared by SARS-CoV and SARS-CoV-2, consistent with the shared ACE2 predicted receptor.
32522617 Like SARS-CoV, ACE2 as a functional receptor for SARS-CoV2 is essential for virus to entry to the cell. […] ACE2 is a part of RAS which is expressed in several organs that opposes the AngII functions by converting Ang II to Ang (1-7), the one with vasodilation effects. […] In addition, cardiovascular involvement by SARS-CoV2 could be direct through either ACE2 receptors which are expressed tremendously in heart, or by the surge of different cytokines or by ARDS-induced hypoxia.
32522846 This article reviews the correlation between ACE2 and COVID-19 and the resulting acute respiratory distress syndrome (ARDS). […] ACE2 is a crucial component of the renin-angiotensin system (RAS). […] The classical ACE-angiotensin Ⅱ (Ang II)-angiotensin type 1 receptor (AT1R) axis and the ACE2-Ang(1-7)-Mas counter-regulatory axis play an essential role in RAS system. […] ACE2 antagonises the activation of the classical RAS ACE-Ang II-AT1R axis and protects against lung injury. […] Similar to severe acute respiratory syndrome-related coronavirus, 2019 novel coronavirus (2019-nCoV) also uses ACE2 for cell entry. […] ARDS is a clinical high-mortality disease which is probably due to the excessive activation of RAS caused by 2019-nCoV infection, and ACE2 has a protective effect on ARDS caused by COVID-19. […] Because of these protective effects of ACE2 on ARDS, the development of drugs enhancing ACE2 activity may become one of the most promising approaches for the treatment of COVID-19 in the near future.
32523925 Pancreatic exocrine tissue and endocrine islets both express angiotensin-converting enzyme 2 (ACE2), the proven receptor for SARS-CoV-2 cell internalization.
32525600 The variations within Angiotensin-converting enzyme 2 (ACE2) gene might constitute the first genetic gateway, influencing the spatial transmission dynamics of COVID-19.
32526012 Although angiotensin-converting enzyme 2 (ACE2) is crucial for SARS-CoV2 to bind and enter host cells, no study has systematically assessed the ACE2 expression in the lungs of patients with these diseases. […] Here, we analyzed over 700 lung transcriptome samples of patients with comorbidities associated with severe COVID-19 and found that ACE2 was highly expressed in these patients, compared to control individuals. […] Correlation and network analyses revealed many potential regulators of ACE2 in the human lung, including genes related to histone modifications, such as HAT1, HDAC2, and KDM5B.
32526206 High-sensitivity RNA in situ mapping revealed the highest angiotensin-converting enzyme 2 (ACE2) expression in the nose with decreasing expression throughout the lower respiratory tract, paralleled by a striking gradient of SARS-CoV-2 infection in proximal (high) versus distal (low) pulmonary epithelial cultures.
32528233 Evidences suggest that the S1 domain of the SARS-CoV-2 (causative agent of COVID-19) membrane spike has a high affinity towards the angiotensin-converting enzyme 2 (ACE2) receptor found on the host’s lung epithelium.
32528815 In the receptor-binding domain (RBD) of the S gene, 11 non-synonymous mutations were observed in the region adjacent to the angiotensin converting enzyme 2 (ACE2) binding site.
32529477 A systematic search in the literature was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science, as well as Google Scholar pre-print database using all available MeSH terms for COVID-19, Coronavirus, SARS-CoV-2, senescent cell, cytokine storm, inflame-aging, ACE2 receptor, autophagy, and Vitamin D.
32531235 Given the severity and the wide and rapid spread of the SARS-CoV-2 infection, it is very likely that the virus recognizes other receptors/co-receptors besides the ACE2.
32531372 Participants from 2 large asthma cohorts were stratified using clinically relevant parameters to identify factors related to ACE2 expression within bronchial epithelium. […] Stratifying by Type 2 inflammatory biomarkers, we identified subjects who demonstrated low peripheral blood eosinophils accompanied by increased expression of the SARS-CoV-2 receptor ACE2 in bronchial epithelium. […] Genes highly correlated with ACE2 overlapped with Type 1 and 2 interferon signatures, normally induced by viral infections. […] T cell recruitment and activation within bronchoalveolar lavage cells of ACE2-high subjects was reciprocally increased. […] ACE2 expression is linked to upregulation of viral response genes in a subset of Type-2 low asthmatics with characteristics resembling known risk factors for severe COVID-19.
32531538 Hesperidin can block coronavirus from entering host cells through ACE2 receptors which can prevent the infection.
32532094 Here we established a quantitative fusion assay dependent on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S protein, angiotensin I converting enzyme 2 (ACE2) and TMPRSS2, and found that nafamostat mesylate potently inhibited the fusion while camostat mesylate was about 10-fold less active.
32532805 The high rate of thrombotic complications associated with COVID-19 seems likely to reflect viral infection of vascular endothelial cells, which express the ACE2 protein that enables SARS-CoV-2 to invade cells.
32533197 The pathophysiology of COVID-19 associated AKI could be related to unspecific mechanisms but also to COVID-specific mechanisms such as direct cellular injury resulting from viral entry through the receptor (ACE2) which is highly expressed in the kidney, an imbalanced renin-angotensin-aldosteron system, pro-inflammatory cytokines elicited by the viral infection and thrombotic events.
32533988 Polymorphisms in ACE2 gene, ACE gene and in genes for some of the host cell proteases could affect the viral entry and replication.
32534021 Due to the cellular entry of the novel coronavirus (SARS-CoV-2) modulated by angiotensin converting enzyme 2 (ACE2), the ACE2 bearing prostate is therefore hypothesized as a susceptible organ to COVID-19.
32534337 SARS-CoV-2 binds its host cell receptor, angiotensin-converting enzyme 2 (ACE2), through the viral spike (S) protein. […] Importantly, rhein inhibits the interaction between the SARS-CoV S protein and ACE2 in a dose-dependent manner, suggesting rhein as a potential therapeutic agent for the treatment of SARS-CoV infection.
32534506 The biologic studies show that the target receptor for the virus might be angiotensin-converting enzyme 2 (ACE2). […] It is emphasized that the direct target of the virus is ACE2 underlining the obvious difference with ACE.
32535705 Levels of angiotensin-converting enzyme 2 (ACE2), a protein that facilitates entry of coronavirus into cells, may increase in patients using RAS inhibitors. […] In this review, we provide a critical review to the following questions: (1) Does hypertension influence immunity or ACE2 expression favoring viral infections? […] From the therapeutic perspective, recombinant ACE2 may serve as a potential therapy, but relevant studies in humans are lacking.
32535979 The virus enters cells, likely including those lining blood vessels, by binding to angiotensin converting enzyme 2 (ACE2) receptors on the cell surface.
32536978 Possible mechanisms of myocardial injury in COVID-19 include ischaemia due to circulatory and respiratory failure, epicardial or intramyocardial small coronary artery thrombotic obstruction due to increased coagulability, and myocarditis caused by systemic inflammation or direct binding of the virus to its receptor, angiotensin-converting enzyme-2 (ACE2), which is abundantly expressed in the heart.
32537478 It has been reported that angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) are the main cell entry proteins for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and play a critical role in causing coronavirus disease 2019 (COVID-19). […] We have found a differential expression of ACE2 and TMPRSS2 in nasal and bronchial airways relative to age and diseases status. […] Moreover, the lung airway expression of both ACE2 and TMPRSS2 was found to be significantly upregulated in smokers compared with non-smokers, and in patients with chronic obstructive pulmonary disease (COPD) compared with healthy subjects. […] No difference was observed in the blood expression levels of ACE2 and TMPRSS2 between children and adults, or in COPD or diabetic patients. […] However, a significant increase in blood expression levels of these genes was observed in patients with essential hypertension, whereas only ACE2 was upregulated in the blood of asthmatics. […] These results suggest that the observed difference in COVID-19 severity between children and adults could, in part, be attributed to the difference in ACE2 and TMPRSS2 airways tissue expression levels.
32538276 These studies reported Cefuroxime as a potential inhibitor of 3 key SARS-CoV-2 proteins; main protease, RNA dependent RNA polymerase, and ACE2-Spike complex.
32538738 We constructed complex models of SARS-CoV-2 spike protein binding to pangolin or human ACE2, the receptor for virus transmission, and estimated the binding free energy changes using molecular dynamics simulation. […] SARS-CoV-2 can bind to both pangolin and human ACE2, but has a significantly lower binding affinity for pangolin ACE2 due to the increased binding free energy (9.5 kcal mol-1). […] Human ACE2 is among the most polymorphous genes, for which we identified 317 missense single-nucleotide variations (SNVs) from the dbSNP database. […] Three SNVs, E329G (rs143936283), M82I (rs267606406) and K26R (rs4646116), had a significant reduction in binding free energy, which indicated higher binding affinity than wild-type ACE2 and greater susceptibility to SARS-CoV-2 infection for people with them.
32538775 It can be misleading to think that the new severe acute respiratory syndrome coronavirus (SARS-CoV2) which has a very strong mutation and adaptation capabilities, uses only the angiotensin-converting enzyme II (ACE2) pathway to reach target cells. […] The main reason why the ACE2 pathway comes to the fore in all scientific studies is that this receptor is located at the entry point of basic mechanisms that provide alveolo-capillary homeostasis. […] SARS-CoV-2 has to use nuclear factor-κB (NF-kB), caveloae, clathrin, lipoxin, serine protease and proteasome pathways in addition to ACE2 to enter the target cell and initiate damage.
32540268 As the viral infection is driven by increased angiotensin-converting enzyme-2 (ACE2) expression, with the kidney exhibiting the highest expression, it is crucial to gain insights into the mechanisms underlying renal cell carcinoma (RCC) and coronavirus disease 2019 (COVID-19).
32540428 The transmembrane spike (S) glycoprotein of SARS-CoV-2 directly binds to the host angiotensin-converting enzyme 2 (ACE2) and mediates viral entrance, which is therefore considered as a promising drug target. […] Through in vitro molecular interaction experiments, eltrombopag was further verified to possess a high binding affinity to S protein plus human ACE2 and could potentially affect the stability of the ACE2-S protein complex.
32540737 Medications, including pioglitazone, that upregulate tissue expression of angiotensin converting enzyme 2 (ACE2), might have a dual role in COVID-19; on the one hand they might increase risk of infection as SARS-CoV2 uses ACE2 as a coreceptor to enter alveolar cells, but on the other hand, by reducing angiotensin II levels, they can protect against acute lung injury. […] There is no evidence to date that pioglitazone upregulates ACE2 in the alveolar cells; rather, there is evidence from animal studies of upregulation of ACE2 in insulin sensitive tissues, which might have a protective effect on lung injury.
32542337 Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) share their target receptor site with the SARS-CoV-2 virus, that may cause ACE2 receptor up-regulation which raised concerns regarding ACEI and ARB use in COVID-19 patients. […] Additionally, the individual patient factors such as ACE2 polymorphisms which might confer higher risk of adverse outcomes need to be evaluated further.
32542396 As for SARS-CoV that caused the SARS 2003 epidemic, the receptor on host cells that promotes uptake, through attachment of the spike (S) protein of the virus, is angiotensin-converting enzyme 2 (ACE2). […] (Lond.) (2020) 134, 543-545) it was suggested that soluble recombinant ACE2 could be used as a novel biological therapeutic to intercept the virus, limiting the progression of infection and reducing lung injury. […] Another way, discussed here, to capture SARS-CoV-2, as an adjunct or alternative, would be to use ACE2+-small extracellular vesicles (sEVs). […] A competitive inhibition therapy could therefore be developed, using sEVs from engineered mesenchymal stromal/stem cells (MSCs), overexpressing ACE2.
32543296 It has been shown that SARS-CoV-2 spike protein shares a high similarity with SARS-CoV spike protein with a strong binding affinity to human Angiotensin Converting Enzyme 2 (ACE2) receptor.
32543348 Single-cell sequencing and ACE2-Furin co-expression results confirmed that the Furin expression was higher in the whole body, especially in glands, liver, kidneys, and colon.
32544372 Ab6 and m397 competed with ACE2 for binding to RBD, suggesting a competitive mechanism of virus neutralization.
32544563 The attachment of SARS-CoV-2 spike glycoprotein with angiotensin-converting enzyme 2 (ACE2), as its cellular receptor, triggers complex molecular events that leads to hyperinflammation. […] The virus-mediated down-regulation of ACE2 causes a burst of inflammatory cytokine release through dysregulation of the renin-angiotensin-aldosterone system (ACE/angiotensin II/AT1R axis), attenuation of Mas receptor (ACE2/MasR axis), increased activation of [des-Arg9]-bradykinin (ACE2/bradykinin B1R/DABK axis), and activation of the complement system including C5a and C5b-9 components.
32544566 We analyzed human post-mortem eyes as well as surgical specimens for the expression of ACE2 (the receptor for SARS-CoV-2) and TMPRSS2, a cell surface-associated protease that facilitates viral entry following binding of the viral spike protein to ACE2. […] Across all eye specimens, immunohistochemical analysis revealed expression of ACE2 in the conjunctiva, limbus, and cornea, with especially prominent staining in the superficial conjunctival and corneal epithelial surface. […] Surgical conjunctival specimens also showed expression of ACE2 in the conjunctival epithelium, especially prominent in the superficial epithelium, as well as the substantia propria. […] Finally, Western blot analysis of protein lysates from human corneal epithelium obtained during refractive surgery confirmed expression of ACE2 and TMPRSS2.
32544615 Extracellular vesicles may contribute to spread this virus as they transfer such receptors as CD9 and ACE2, which make recipient cells susceptible to virus docking.
32545268 Our in silico studies show that these flavonoid-based molecules can bind with high affinity to the spike protein, helicase, and protease sites on the ACE2 receptor used by the severe acute respiratory syndrome coronavirus 2 to infect cells and cause COVID-19.
32545271 We surveyed the co-expression of SARS-CoV-2 entry genes ACE2 and TMPRSS2 throughout the GI tract to assess potential sites of infection. […] Enterocytes from the small intestine and colonocytes showed the highest proportions of cells co-expressing ACE2 and TMPRSS2.
32545518 We found that the potent Nrf2-activating composition PB125® downregulates ACE2 and TMPRSS2 mRNA expression in human liver-derived HepG2 cells. ACE2 is a surface receptor and TMPRSS2 activates the spike protein for SARS-CoV-2 entry into host cells.
32546047 While the potential therapeutic utility of angiotensin-converting enzyme 2 (ACE2) is well established, the clinical development of ACE2 drugs has been limited, likely due in part to the short half-life of the protein. […] In contrast, Ig-like ACE2 fusion proteins have exhibited greatly extended plasma half-life in vivo, and they have been shown to have a potent neutralization effect against SARS-CoV-2. […] Clinical investigation of Ig-like ACE2 fusion proteins as COVID-19 interventions is thus warranted.
32546188 Ongoing trials directly and indirectly target COVID-19-related endothelial dysfunctions: i.e., a virus-cell entry using recombinant angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS-2) blockade, coagulation activation, and immunomodulatory therapies, such as anti-IL-6 strategies.
32547717 The ACE2 receptor plays a central role in severe acute respiratory syndrome coronavirus 2 host cell entry and propagation. […] It has therefore been postulated that angiotensin converting enzyme inhibitors and angiotensin receptor blockers may upregulate ACE2 expression and thus increase susceptibility to infection.
32549071 The SARS-CoV-2 uses the same host receptor, angiotensin-converting enzyme 2 (ACE2), used by SARS-CoV to infect humans.
32549125 In this opinion paper, we describe how sex-specific immunobiological factors and differences in angiotensin converting enzyme 2 (ACE2) expression may explain the increased severity and mortality of COVID-19 in males.
32549297 In this review, we have analyzed some lesser known aspects of the relationship between neoplasms and SARS-CoV-2 infection, starting from the different expression of the ACE2 receptor of the virus in the various neoplastic pathologies, and the roles that different cytokine patterns could have in vulnerability to infection and the appearance of complications.
32550040 Though its pathogenesis has not been fully elucidated, angiotensin-converting enzyme 2 (ACE2) has been recently identified as a receptor for the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the cell. […] Here, we aimed to clarify the potential role of ACE2 in SARS-CoV-2-induced acute lung injury and its underlying mechanism. […] As a receptor for coronavirus, ACE2 mediates the entry of SARS-CoV-2 into cells in a similar way as for severe acute respiratory syndrome coronavirus (SARS-CoV). […] The high binding affinity of SARS-CoV-2 to ACE2 correlates with its efficient spread among humans. […] On the other hand, ACE2 negatively regulates the renin-angiotensin-aldosterone system (RAAS) primarily by converting angiotensin II to angiotensin 1-7, which exerts a beneficial effect on coronavirus-induced acute lung injury. […] Human recombinant ACE2 has been considered as a potential therapy for SARS-CoV-2 by blocking virus entry and redressing the imbalance of RAAS in SARS-CoV-2 infection. […] The level of ACE2 expression can be upregulated by treatment with an ACE inhibitor (ACEI) or angiotensin Ⅱ type 1 receptor blocker (ARB).
32550056 It acts by attaching to the angiotensin-converting enzyme (ACE2) with the help of glycoprotein spikes, which it uses as a receptor.
32550259 The mechanism of cardiac involvement in COVID-19 patients involves direct injury to myocardial cells mediated by angiotensin-converting enzyme 2 (ACE2) receptors as suggested by some studies, while the other studies suggest that systemic inflammation causing indirect myocyte injury may also play a role.
32551560 In this study, we identified high-binding-affinity aptamers targeting SARS-CoV-2 RBD, using an ACE2 competition-based aptamer selection strategy and a machine learning screening algorithm. […] Simulated interaction modeling, along with competitive with experiments, suggests that two aptamers may have partially identical binding sites at ACE2 on SARS-CoV-2 RBD.
32551648 The viral entry and thus infectivity is based on the formation of the complex of the SARS-CoV-2 spike protein with the angiotensin-converting enzyme 2 (ACE2). […] The detection of putative allosteric sites on the viral spike protein can trace the path to develop allosteric drugs to weaken spike-ACE2 interaction and, thus, to reduce the viral infectivity. […] In this work we present results of the application of the Protein Contact Network (PCN) paradigm together with SEPAS (affinity by flexibility) and Perturbation Response Scanning (PRS) based on Elastic Network modes to the complex SARS-CoV spike - ACE2 relative to both 2003 SARS and the recent SARS-CoV-2. […] All the adopted analysis paradigms converge toward a specific region, present in both structures, that is predicted to act as allosteric site modulating the binding of the spike protein with ACE2.
32551652 In this work we used a coarse grained model to calculate the binding free energy of SARS-CoV-2 or SARS-CoV to their human receptor ACE2. […] Such evolution may facilitate the conformational change and the infection process that occurs after the virus is bound to ACE2.
32552811 Sub-chronic e-cig exposure with nicotine increased inflammatory cellular influx of macrophages and T-lymphocytes including increased pro-inflammatory cytokines in BALF and increased SARS-Cov-2 Covid-19 ACE2 receptor, whereas nAChRα7 KO mice show reduced inflammatory responses associated with decreased ACE2 receptor.
32553273 Commercially available laboratory strains of mice are not readily infected by SARS-CoV-2 because of species-specific differences in their angiotensin-converting enzyme 2 (ACE2) receptors. […] Here, we transduced replication-defective adenoviruses encoding human ACE2 via intranasal administration into BALB/c mice and established receptor expression in lung tissues. hACE2-transduced mice were productively infected with SARS-CoV-2, and this resulted in high viral titers in the lung, lung pathology, and weight loss.
32553503 These very legitimate questions are directly the consequence of the recent recognition of the fundamental role of ACE2 (angiotensin-converting enzyme 2) in COVID-19 infection. […] Indeed, SARS COV2 utilizes ACE2 as a membrane receptor to enter target cells. […] As a membrane-bound enzyme (carboxypeptidase), ACE2 inactivates angiotensin II and therefore physiologically counters its effects. […] Due to a different structure compared with ACE1, ACE2 is insensitive to ACEIs. […] In vitro, both ARBs and ACEi appear able to upregulate ACE2 tissue expression and activity but these results were not confirmed in Humans. […] Due to the crucial role of ACE2, some groups support the hypothesis that a modulation of ACE2 expression could represent a valuable therapeutic target could confer protective properties against inflammatory tissue damage in COVID-19 infection. […] So, studies are currently ongoing to test the impact of elevated ACE2 membrane expression, administration of ARB and infusion of soluble ACE2.
32553666 The postulated mechanism of viral entry is through the host ACE2 receptors that are abundantly present in type 2 alveolar cells. […] Interestingly, the expression of ACE2 receptors were identified in the gastrointestinal tract, vascular endothelium and cholangiocytes of the liver.
32553928 In this study was to develop a search for new pharmacological compounds against the angiotensin-converting enzyme 2 (ACE2), to inhibit the interaction with SARS-CoV-2. […] Docking, virtual screening using almost 500,000 compounds directed to interact in the region between the residues (Gln24, Asp30, His34, Tyr41, Gln42, Met82, Lys353, and Arg357) in ACE2. […] The average of ΔGbinding, the standard deviation value and the theoretical toxicity from compounds were analyzed. 20 best compounds directed to interact in ACE2 with a high probability to be safe in humans, validated by web servers of prediction of ADME and toxicity (ProTox-II and PreADMET), to difficult the interaction between ACE2 and region binding domain (RBD) of SARS-CoV-2. […] In this study, 20 compounds were determined by docking focused on the region of interaction between ACE2 and RBD of SARS-CoV-2 was carried out.
32554251 QFPD contained 257 specific targets in addition to HCoV, pneumonia and ACE2 co-expression proteins.
32556552 The risk to infect transplant recipients with SARS-CoV‑2 still appears very unlikely due to the experience with severe acute respiratory syndrome -coronavirus(‑1) (SARS-CoV(‑1)) and Middle East respiratory syndrome-coronavirus (MERS-CoV); however, due to the occurrence of angiotensin-converting enzyme 2 (ACE2) receptors in the cornea an infection of this tissue with SARS-CoV‑2 cannot be completely excluded.
32558150 Its pathogen, SARS-CoV-2, has been shown to use angiotensin-converting enzyme 2 (ACE2) as its host cell receptor, same as the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003. […] Here by analyzing GTEx and other public data in 30 tissues across thousands of individuals, we found a significantly higher level in Asian females, an age-dependent decrease in all ethnic groups, and a highly significant decrease in type II diabetic patients of ACE2 expression. […] Consistently, the most significant expression quantitative loci (eQTLs) contributing to high ACE2 expression are close to 100% in East Asians, >30% higher than other ethnic groups. […] A shockingly common enrichment of viral infection pathways was found among ACE2 anti-expressed genes, and multiple binding sites of virus infection related transcription factors and sex hormone receptors locate at ACE2 regulatory regions. […] Human and mice data analysis further revealed ACE2 expression is reduced in T2D patients and with inflammatory cytokine treatment and upregulated by estrogen and androgen (both decrease with age). […] Our findings revealed a negative correlation between ACE2 expression and COVID-19 fatality at both population and molecular levels. […] These results will be instrumental when designing potential prevention and treatment strategies for ACE2 binding coronaviruses in general.
32558308 We examined genetic differences in the human angiotensin-converting enzyme 2 (hACE2) gene, as its receptor serves as a cellular entry for SARS-CoV-2. […] At present, there is a paucity of data regarding the differences for ACE2 polymorphisms and expression levels between ethnicities. […] The binding free energies were calculated between S protein and hACE2. […] We also examined hACE2 gene expression in eight global populations from HapMap3. […] Molecular dynamic demonstrated that two of these variants (K26R and I468V) may affect binding characteristics between S protein of the virus and hACE2 receptor. […] Our studies reveal subtle changes in the genetics of hACE2 between human populations, but the magnitude of the difference was small and the significance is not clear in the absence of further in vitro and functional studies.
32558946 Investigation of this viral infection in the human bronchial epithelial cell line (16HBE) suggests that SARS-CoV-2 can enter these cells through interaction between its membrane-localized S protein with the ACE2 molecule on the host cell membrane.
32561270 The most potent antibody bound the RBD and prevented binding to the ACE2 receptor, while the other bound outside the RBD. […] Antibodies that disrupt the SARS-CoV-2 S-ACE2 interaction can potently neutralize the virus without undergoing extensive maturation.
32561291 SARS-CoV-2 entry starts with the binding of the spike glycoprotein expressed on the viral envelope to ACE2 on the alveolar surface followed by clathrin-dependent endocytosis of the SARS-CoV-2 and ACE2 complex.
32561317 Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are considered first-line agents in patients with diabetes because of their nephroprotective effects, but administration of these drugs leads to upregulation of angiotensin-converting enzyme 2 (ACE2), which is responsible for the viral entry of severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2).
32562137 Angiotensin converting enzyme 2 (ACE2) is a target cell receptor for internalization and proliferation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). […] When ACE2-highly expressed tissues are manipulated, SARS-CoV-2 containing aerosols may be generated.
32562276 Briefly, statins could act modulating virus entry, acting on the SARS-CoV-2 receptors, ACE2 and CD147, and/or lipid rafts engagement.
32562701 Apelin or its receptor agonists are of great potential treatment for COVID-19 through suppressing angiotensin-converting enzyme (ACE) and angiotensin II (Ang-II) production, as well as, down-regulating angiotensin receptor 1 (AT1R) and ACE2 up-regulation.
32562913 As it is evident from the recent studies that SARS-CoV-2 requires host enzyme Furin to activate receptor binding domain of its S protein and host Angiotensin Convertase Enzyme 2 (ACE2) is required as binding receptor, facilitating the entry of virus into the host cell. […] Evidence from literature shows that oral cancer tissues as well as paracarcinoma tissue exhibit higher expression of both Furin and ACE2, giving rise to the hypothesis that patients with oral cancer have higher chances of SARS CoV2 infection.
32562915 The virus attacks type II pneumocytes in the lower bronchi through the binding of the Spike protein (S protein) to viral receptors, of which the angiotensin 2 conversion enzyme (ACE2) receptor is the most important. […] ACE2 receptor is widely expressed in numerous tissues, including the oropharynx and conjunctiva, but mostly distributed in ciliated bronchial epithelial cells and type II pneumocytes in the lower bronchi.
32563970 In which, pros and cons were discussed and inferred the possible alternatives. (a) Specificity: Implicit to express the ACE2 receptors in conveyor cells to deceive SARS-CoV-2 frompreponetargets. (b) Remedy: As depletion of pulmonary surfactants causes strong acute respiratory distress syndrome, we propose an entity of a cost-effective artificialsurfactantsystem as a remedy to pulmonary complications. (c) Conveyor: We propose red blood cells (RBCs) as a conveyor with embedded artificial surfactant and protruding ACE2 receptors for the target-specific delivery.
32564046 It is known from experimental studies that SARS-Cov-2 enters the cells by interacting with the ACE2 enzyme, while it is not known whether ACE2 is the only factor that allows the virus to enter the cell. […] It has been shown that the use of recombinant ACE2 can be potentially beneficial in COVID-19 therapy by limiting the entry of the virus into the cell.
32564694 To further investigate this sex difference, we examined the role of ACE2 in Ang-[1-8] (angiotensin [1-8])-induced hypertension and regulation of the renin-angiotensin system in the kidney of WT (wild type) and Ace2 KO (knockout) mice. […] This sex difference was attenuated in ACE2 KO mice. […] Ang-[1-8] infusion reduced glomerular AT1R (angiotensin type 1 receptor) binding in WT female mice by 30%, and deletion of Ace2 abolished this effect. […] In contrast, Ang-[1-8] infusion increased glomerular AT1R binding in WT male mice by 1.2-fold, and this effect of Ang-[1-8] persisted in Ace2 KO male mice (1.3-fold). […] ACE2 also had an effect on renal protein expression of the neutral endopeptidase NEP (neprilysin), the enzyme that catabolizes Ang-[1-10] (angiotensin [1-10]), the precursor of Ang-[1-8]. […] Deletion of Ace2 resulted in lowered NEP expression after Ang-[1-8] infusion in both sexes. […] These findings suggest sex-specific ACE2 regulation of the renin-angiotensin system contributes to female protection from Ang-[1-8]-induced hypertension. […] These findings have ramifications for the current coronavirus disease 2019 (COVID-19) pandemic, especially in hypertension since ACE2 is the SARS-CoV-2 receptor and hypertension is a major risk factor for poor outcomes.
32565362 SARS-CoV-2 employs the host cell receptor ACE2 for cellular entry. […] Nonetheless, the differences in ACE2 expression pattern in lung versus other normal and solid tumor tissues remain incompletely characterized. […] Here, we analyze a large data set comprising ACE2 mRNA expression for 7592 tissue samples across 22 types of primary solid tumor and 4461 samples across matched 18 non-diseased tissues.
32566425 COVID-19, like other coronaviruses, presents with S glycoproteins on the membrane that plays an integral role in the virus binding with the angiotensin-converting enzyme 2 (ACE2) receptor. […] The ACE2 receptor is an intramembrane receptor on the type II pneumocytes, where the virus is able to replicate after getting endocytosed within the cytoplasm.
32566896 SARS-CoV-2 gains entry to human cells through its spike (S) protein binding to angiotensin-converting enzyme 2 (ACE2).
32567171 Whilst research all over the world is still struggling to provide a detailed characterization of the biology of SARS-CoV2 and its associated disease profile, it has become evident that SARS-CoV2 uses the membrane-bound form of angiotensin-converting enzyme 2 (ACE2) as a receptor for cell internalization. […] ACE2 is a protective component of the RAAS axis and is downregulated after SARS-CoV2 infection.
32567823 However, SARS-CoV-2 can affect several human organs due to high expressions of ACE2 receptor which is the main viral target and the virus may affect not only higher and lower respiratory tracts, but also heart, kidney, gastro enteric tract, liver, pancreas, nervous system and skin.
32567938 The virus binds to the cellular receptor ACE2, which in children has a structural and functional immaturity thus offering lower affinity to the pathogen; this could explain the lower incidence of infection from SARS-CoV-2 in this segment of the population.The common clinical observation is that COVID-19 is less severe in children, and in this group the disease is often asymptomatic.
32568687 Preliminary conformational analysis of the receptor (ACE2) binding site of the spike protein is carried out suggesting that while it is somewhat conserved, it appears to be more variable than KRSFIEDLLFNKV. […] However compounds like emodin that inhibit SARS entry, apparently by binding ACE2, might also have functions at several different human protein binding sites.
32569293 We seek to raise awareness about the male-biased severe outcomes from COVID-19, highlighting the mechanistic differences including in the expression and activity of angiotensin-converting enzyme 2 (ACE2) as well as in antiviral immunity.
32570174 The resemblance with SARS-CoV in spike protein suggests that SARS-CoV-2 employs spike-driven entry into angiotensin-converting enzyme 2 (ACE2)-expressing cells. […] From a stem cell perspective, this review focuses on the possible involvement of ACE2+ stem/progenitor cells from both the upper and lower respiratory tracts in coronavirus infection.
32570882 It has been shown that high cholesterol levels are associated with more lipid rafts, subdomains of the plasma membrane that can harbour angiotensin-converting enzyme 2 (ACE2) receptors for the S-protein of SARS-CoV-2.
32572334 In this study, we combined system biology and bioinformatic approaches to define the role of coexpression of angiotensin-converting enzyme 2 (ACE2), neprilysin or membrane metallo-endopeptidase (MME), and carbonic anhydrases (CAs) and their association in the pathogenesis of SARS-CoV-2. […] The results revealed that ACE2 as the cellular attachment site of SARS-CoV-2, neprilysin, and CAs have a great contribution together in the renin angiotensin system (RAS) and consequently in pathogenesis of SARS-CoV-2 in the vital organs such as respiratory, renal, and blood circulation systems. […] Any disorder in neprilysin, ACE2, and CAs can lead to increase of CO2 concentration in blood and respiratory acidosis, induction of pulmonary edema and heart and renal failures. […] Due to the presence of ACE2-Neprilysin-CA complex in most of vital organs and as a receptor of COVID-19, it is expected that most organs are affected by SARS-CoV-2 such as inflammation and fibrosis of lungs, which may conversely affect their vital functions, temporary or permanently, sometimes leading to death. […] Therefore, ACE2-Neprilysin-CA complex could be the key factor of pathogenesis of SARS-CoV-2 and may provide us useful information to find better provocative and therapeutic strategies against COVID-19.
32572383 The inhibitory capability of active compounds in the TA from Thua Thien Hue, Vietnam over the Angiotensin-Converting Enzyme 2 (ACE2) protein in human body - the host receptor for SARS-CoV-2 and the main protease (PDB6LU7) of the SARS-CoV-2 using docking simulation has been studied herein. […] The results indicate that the ACE2 and PDB6LU7 proteins were strongly inhibited by 10 out of 24 compounds accounting for 70.9% in the TA. […] Interestingly, the synergistic interactions of these 10 substances of the TA exhibit excellent inhibition into the ACE2 and PDB6LU7 proteins.
32572552 The current body of evidence indicates that SARS-CoV‑2 requires the membrane-bound angiotensin-converting enzyme 2 (ACE2) and the membrane-bound serine protease TMPRSS2 to enter cells. […] Recent studies suggest that COVID-19 patients rarely exhibit viral RNA in tear film and conjunctival smears and that, ACE2 and TMPRSS2 are only expressed in very small amounts in the conjunctiva, making conjunctival infection with SARS-CoV‑2 via these mediators unlikely.
32573351 Totally 47 bioactives identified from the medicinal plants were investigated against the structural targets of SARS-CoV-2 (Mpro and spike protein) and human ACE2 receptor.
32573711 The receptor for SARS-CoV-2 binding, ACE2, was not detected by mRNA or protein in platelets. […] Surprisingly, mRNA from the SARS-CoV-2 N1 gene was detected in platelets from 2/25 COVID-19 patients, suggesting platelets may take-up SARS-COV-2 mRNA independent of ACE2.
32573788 The SARS-CoV-2 uses the host angiotensin-converting enzyme 2 (ACE2) receptor to gain entry inside the human cells where it replicates by using the cell protein synthesis mechanisms. […] The knowledge of the tissue distribution of ACE2 in human organs is therefore important to predict the clinical course of the COVID-19. […] We performed an exhaustive search of human protein databases to establish the tissues that express ACE2 and performed an in-depth analysis like sequence alignments and homology modeling of the spike protein (S) of the SARS-CoV-2 to identify antigenic regions in the RBD that can be exploited to synthesize vaccine and mAbs. […] Our results show that ACE2 is widely expressed in human organs that may explain the pulmonary, systemic, and neurological deficits seen in COVID-19 patients.
32574107 SARS-CoV2 binding to ACE2 can lead to excessive angiotensin II signaling, which activates the STING pathway in mice.
32574196 Both ACE2 (an entry receptor) and TMPRSS2 (used by the virus for spike protein priming) are key proteins to SARS-CoV-2 cell entry, enabling progression to COVID-19 in humans. […] Comparative genomic research into critical ACE2 binding sites, associated with the spike receptor binding domain, has suggested that African and Asian primates may also be susceptible to disease from SARS-CoV-2 infection. […] To characterize potential functional variation in savanna monkey ACE2 and TMPRSS2, we inspected recently published genomic data from 245 savanna monkeys, including 163 wild monkeys from Africa and the Caribbean and 82 captive monkeys from the Vervet Research Colony (VRC). […] One missense variant in ACE2 (X:14,077,550; Asp30Gly), common in Ch. sabaeus, causes a change in amino acid residue that has been inferred to reduce binding efficiency of SARS-CoV-2, suggesting potentially reduced susceptibility. […] All missense variants observed in wild Ch. sabaeus populations are also present in the VRC, along with two splice acceptor variants (at X:14,065,076) not observed in the wild sample that are potentially disruptive to ACE2 function.
32574268 IP is caused by the viral glycoprotein spike (S) binding to the angiotensin converting enzyme 2 (ACE2) expressed on the surface of alveolar pneumocytes.
32574271 Of importance are Heparan Sulfate Proteoglycans (HSPGs) and the host receptor angiotensin-converting enzyme 2 (ACE2), as based on other activities lactoferrin might prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from attaching to the host cells.
32574272 Virus protein ligands (e.g., haemagglutinin or trimeric spike glycoprotein for Influenza and CoV, respectively) interact with cellular receptors, such as (depending on the virus) either sialic acids, Dipeptidyl peptidase 4 (DPP4), or angiotensin-converting enzyme 2 (ACE2).
32574273 The role of the ACE2 enzyme in the COVID-19 infection is 2-fold, with opposing implications for the disease development. […] The membrane bound angiotensin converting enzyme 2 (ACE2) serves as the entry point of COVID-19 2. […] ACE2 is part of the wider renin-angiotensin-aldosterone system (RAAS) and is upregulated via compounds, which inhibits the classical ACE, thereby plasma aldosterone and aldosterone receptor (MR) activation. […] MR activation may therefore protect organs from binding the COVID-19 by reducing ACE2 expression. […] Does this affect the protective effect of ACE2? […] Importantly, GL has anti-inflammatory properties by itself via toll like receptor 4 (TLR4) antagonism and therefore compensates for the reduced protection of the downregulated ACE2. […] To block the number of entry points and 2. provide an ACE2 independent anti-inflammatory mechanism.
32574336 Angiotensin-converting enzyme 2 (ACE2) is the receptor for COVID-19 (SARs-CoV-2). […] ACE2 protects the lung and heart from acute respiratory distress syndrome (ARDS) and acute myocarditis and arrhythmias, because it breaks down Angiotensin II, which has inflammatory effects in the lung and heart as well as in the kidney. […] When SARS-CoV-2 binds to ACE2, it suppresses it, so this protective action of ACE2 is lost.
32574379 These findings are applicable to a parallel strategy for the generation of polysaccharides similar to those present in the receptor-binding domain of CoViD-19, which might inhibit viral adhesion to its receptor, the angiotensin-converting enzyme-2 (ACE2) protein, thereby impairing cellular uptake of the virus itself.
32574956 Flow cytometry analyses were performed to detect the direct binding of S protein and the expression of ACE2 on the cell surface of macrophages. […] S protein of SARS-CoV-2 directly bound to the macrophage via the S-protein-ACE2 interaction.
32575476 The angiotensin-converting enzyme 2 (ACE2) receptor, a host cell receptor, has been found to play a crucial role in virus cell entry; therefore, ACE2 blockers can be a potential target for anti-viral intervention. […] In this study, we evaluated the ACE2 inhibitory effects of 10 essential oils. […] Among them, geranium and lemon oils displayed significant ACE2 inhibitory effects in epithelial cells. […] In addition, immunoblotting and qPCR analysis also confirmed that geranium and lemon oils possess potent ACE2 inhibitory effects. […] Next, we found that treatment with citronellol and limonene significantly downregulated ACE2 expression in epithelial cells.
32576357 2019 Novel coronavirus (2019-nCoV) destroys angiotensin converting enzyme 2 (ACE2) and breaks the balance of renin-angiotension system (RAS) by interacting with ACE2.
32577056 The ACE2 receptors were widely disturbed among body tissues such as lung, kidney, small intestine, heart, and others in different percent and considered a target for the nCOVID-19 virus. […] S-protein of the virus was binding to ACE2 receptors caused downregulation of endogenous anti-viral mediators, upregulation of NF-κB pathway, ROS and pro-apoptotic protein. […] We used method of analysis of the published papers with described studies about COVID-19 connected with pharmacological issues and aspects which are included in global fighting against COVID-19 infection, and how using DMF (Nrf2 activator) in clinical trial for nCOVID-19 produce positive effects in patients for reduce lung alveolar cells damage. we are found that Nrf2 activators an important medication that’s have a role in reduce viral pathogenesis via inhibit virus entry through induce SPLI gene expression as well as inhibit TRMPSS2, upregulation of ACE2 that’s make a competition with the virus on binding site, induce gene expression of anti-viral mediators such as RIG-1 and INFs, induce anti-oxidant enzymes, also they have a role in inhibit NF-κB pathway, inhibit both apoptosis proteins and gene expression of TLRs.
32577830 Similarly, a decrease in the oral viral load would diminish the amount of virus expelled and reduce the risk of transmission, since (i) during the first 10 days, the virus mainly accumulates at the nasal, oral, and pharyngeal area; (ii) the number of angiotensin-converting enzyme (ACE2) receptor is greater in the salivary glands as compared with the lungs; and (iii) salivary droplets represent the most relevant transmission route.
32578263 SARS-CoV-2 enters the cells with the help of ACE2; therefore, testicular expression of ACE2 was analysed from transcriptome sequencing studies and our unpublished data. […] We also found ACE2 expression in transcriptome sequencing data for human spermatozoa, corroborating its presence in the testicular germ cells. […] Transcriptome sequencing data from literature search revealed ACE2 expression in the germ, Sertoli and Leydig cells. […] The presence of ACE2 on almost all testicular cells and the report of a significant impact of previous SARS coronavirus on testes suggest that SARS-CoV-2 is highly likely to affect testicular tissue, semen parameters and male fertility.
32579957 Up-to-date, a number of mechanisms have been postulated for COVID-19-associated cardiovascular damage including SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) activation, cytokine storm, hypoxemia, stress and cardiotoxicity of antiviral drugs.
32580257 SARS-CoV-2 infects host cells by targeting the angiotensin-converting enzyme 2 (ACE2) receptor, which is present on endothelial cells in the lung, heart, kidney, and gastrointestinal tissue. […] These high-risk populations are often on angiotensin-modulating therapies, which are theorized to increase ACE2 expressivity, but current evidence for or against discontinuation is equivocal.
32580440 Furthermore, we analyze the positive correlation between the virus spread, PM, and angiotensin-converting enzyme 2 (ACE2), a receptor involved in the entry of the virus into pulmonary cells and inflammation.
32582134 SARS-CoV and SARS-CoV-2 have 79.5% nucleotide sequence identity and use angiotensin-converting enzyme 2 (ACE2) receptors to enter host cells. […] The distribution of ACE2 may determine how SARS-CoV-2 infects the respiratory and digestive tract. […] ACE2 regulates the gut microbiota by indirectly controlling the secretion of antimicrobial peptides.
32582222 A common denominator of all affected organs is the expression of angiotensin-converting enzyme 2 (ACE2), a protease responsible for the conversion of Angiotensin 1-8 (Ang II) to Angiotensin 1-7 (Ang 1-7). […] Unfortunately, ACE2 also serves as the binding receptor of SARS viral spike glycoprotein, enabling its attachment to host cells, with subsequent viral internalization and replication. […] Although numerous reports have linked the devastating organ injuries to viral homing and attachment to organ-specific cells widely expressing ACE2, little attention has been given to ACE-2 expressed by the immune system. […] Herein we outline potential adverse effects of SARS-CoV2 on macrophages and dendritic cells, key cells of the immune system expressing ACE2. […] It is tempting to assume that diverse expression of ACE2 in macrophages among individuals might govern the severity of SARS-CoV-2 infection.
32582302 The SARS-CoV-2 virus responsible for the infection depends on two human genes: the human receptor angiotensin converting enzyme 2 (ACE2) for cell invasion, and the serine protease TMPRSS2 for S protein priming. […] We examined 178 quantitative phenotypes including cytokines and cardio-metabolic biomarkers, as well as usage of 58 medications in 36,339 volunteers from the Lifelines population cohort, in relation to 1,273 genetic variants located in or near ACE2 and TMPRSS2. […] SNPs within the ACE2 gene were associated with (1) the use of angiotensin II receptor blockers (ARBs) combination therapies (p = 5.7 × 10-4), an association that is significantly stronger in females (p dif f = 0.01), and (2) with the use of non-steroid anti-inflammatory and antirheumatic products (p = 5.5 × 10-4).
32582574 We review the physiological functions of ACE2 in the cardiovascular system and the lungs, and how the activation of ACE2/MAS/G protein coupled receptor contributes in reducing acute injury and inhibiting fibrogenesis of the lungs and protecting the cardiovascular system. […] In this perspective, we predominantly focus on the impact of SARS-CoV-2 infection on ACE2 and dysregulation of the protective effect of ACE2/MAS/G protein pathway vs. the deleterious effect of Renin/Angiotensin/Aldosterone. […] We discuss the potential effect of invasion of SARS-CoV-2 on the function of ACE2 and the loss of the protective effect of the ACE2/MAS pathway in alveolar epithelial cells and how this may amplify systemic deleterious effect of renin-angiotensin aldosterone system (RAS) in the host. […] Furthermore, we speculate the potential of exploiting the modulation of ACE2/MAS pathway as a natural protection of lung injury by modulation of ACE2/MAS axis or by developing targeted drugs to inhibit proteases required for viral entry.
32582576 SARS-CoV-2 enters the lungs through the ACE2 enzyme, a member of the renin-angiotensin system (RAS). […] However, there are no data on sex-specific differences in ACE2 expression. […] If there is a sex difference in the expression of ACE2 in the lung, this could theoretically explain the gender disparity in COVID-19 disease. […] More importantly, although modulation of ACE2 will certainly not provide a cure for the COVID-19 disease, modulation of ACE2 by sex hormone modulators, if they affect the expression of ACE2, could potentially be developed into a supportive therapy for COVID-19 patients.
32583042 At the time of the research, angiotensin-converting enzyme 2 (ACE2) was clearly identified as the receptor and transmembrane serine protease 2 (TMPRSS2) as the necessary protease to enable the infection of human cells with SARS-CoV‑2. […] In the eye both ACE2 and TMPRSS2 are expressed, although sometimes very weakly and with varying degrees in different tissues. […] According to current state of knowledge the eye is not considered to be a high-risk tissue due to the low ACE2 and TMPRSS2 expression.
32584474 Angiotensin-converting enzyme 2 (ACE2), a part of the renin-angiotensin system (RAS), serves as the major entry point into cells for SARS-CoV-2 which attaches to human ACE2, thereby reducing the expression of ACE2 and causing lung injury and pneumonia. […] It can induce ACE2/Ang-(1-7)/MasR axis activity and inhibits renin and the ACE/Ang II/AT1R axis, thereby increasing expression and concentration of ACE2, MasR and Ang-(1-7) and having a potential protective role against acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). […] Therefore, targeting the unbalanced RAS and ACE2 down-regulation with vitamin D in SARS-CoV-2 infection is a potential therapeutic approach to combat COVID-19 and induced ARDS.
32586214 The evidence to date supports the concept that the thrombotic manifestations of severe COVID-19 is due to the ability of SARS-CoV-2 to invade endo¬thelial cells via angiotensin-converting enzyme 2 (ACE2), which is expressed on the endothelial cell surface.
32586380 First, we sought to identify existing FDA approved drugs that could block coronaviruses from entering cells by binding to ACE2 or TMPRSS2 using a high-throughput AI-based binding affinity prediction platform. […] Top results for ACE2 binding iincluded several ACE inhibitors, a beta-lactam antibiotic, two antiviral agents (Fosamprenavir and Emricasan) and glutathione. […] The platform also assessed specificity for ACE2 over ACE1, important for avoiding counterregulatory effects. […] Further studies are needed to weigh the benefit of blocking virus entry against potential counterregulatory effects and possible protective effects of ACE2.
32587077 These are based on the fact that ACE2 facilitates SARS-CoV-2 cell invasion via binding of a viral spike protein to ACE2. […] However, the effect of ACE inhibitors, ARBs and other drugs on ACE2 is unclear and all theories are based on conflicting evidence mainly from animal studies.
32587094 In characterizing viral S protein, we developed a quantitative dynamics cross-correlation matrix to gain insights into its interactions with the angiotensin I-converting enzyme 2 (ACE2)-solute carrier family 6 member 19 (SLC6A19) dimer. […] Using this quantitative matrix, we elucidated 47 potential functional missense variants from genomic databases within ACE2/SLC6A19/transmembrane serine protease 2 (TMPRSS2), warranting genomic enrichment analyses in SARS-CoV-2 patients. […] These variants had ultralow frequency but existed in males hemizygous for ACE2. […] Two ACE2 noncoding variants (rs4646118 and rs143185769) present in ~9% of individuals of African descent may regulate ACE2 expression and may be associated with increased susceptibility of African Americans to SARS-CoV-2.
32587651 Angiotensin-converting enzyme 2 (ACE2) receptors, direct viral damage, and immune-mediated damage play important roles in the pathogenesis.
32589459 The spike proteins of SARS-CoV-2 interact with ACE2 or basigin/CD147 receptors, regulating human-to-human transmissions of COVID-19 together with serine protease TMPRSS2. […] ACE2 is expressed in conjunctival samples at a low level, while BSG and TMPRSS2 are expressed at intermediate levels in both conjunctiva and cornea.
32590326 The SARS virus binds to angiotensin-converting enzyme (ACE2) receptor and causes pneumonia. […] In the lung, the ACE2 receptor sits on the top of lung cells known as alveolar epithelial type II (AE2) cells. […] On the contrary, new SARS-CoV-2 can suppress the production of surfactant that binds to the ACE2 of AE2 cells.
32591346 To facilitate proteomic research on SARS-CoV-2, this report presents deep-scale proteomes (10,000 proteins; >130,000 peptides) of common cell line models, notably Vero E6, Calu-3, Caco-2, and ACE2-A549 that characterize their protein expression profiles including viral entry factors such as ACE2 or TMPRSS2.
32591666 Another aspect of the included studies was the susceptibility of oral tissues to 2019-nCoV due to the expression of angiotensin-converting enzyme II (ACE2) as a receptor for the 2019-nCoV. […] Regarding the possibility of direct virus invasion into the oral tissues, the results suggested that ACE2+ cells in salivary glands could possibly be the target cells of 2019-nCoV and theoretically could generate infectious saliva in a sustained way.
32591762 In patients with COVID-19, epithelial cells showed an average three-fold increase in expression of the SARS-CoV-2 entry receptor ACE2, which correlated with interferon signals by immune cells.
32591839 Reports that the ACE2 receptor - critical for virus entry into lung cells - is found in different neurons supports this expectation. […] We detected the expression of the ACE2 receptor but not TMPRSS2 in the model.
32591908 Angiotensin-converting enzyme 2 (ACE2) is a key counter-regulatory component of the renin-angiotensin system. […] Here, we briefly review the mechanistic and target organ effects related to ACE2 activity, and the importance of ACE2 in SARS-CoV-2 infection. […] ACE2 converts angiotensin (Ang) II to Ang-(1-7), which directly opposes the vasoconstrictive, proinflammatory, and prothrombotic effects of Ang II. […] ACE2 also facilitates SARS-CoV-2 viral entry into host cells. […] Drugs that interact with the renin-angiotensin system may impact ACE2 expression and COVID-19 pathogenesis; however, the magnitude and direction of these effects are unknown at this time. […] High quality research is needed to improve our understanding of how agents that act on the renin-angiotensin system impact ACE2 and COVID-19-related disease outcomes.
32592038 Entrance of SARS-CoV-2 depends on the surface (S) protein interaction with host ACE2 protein and cleavage by TMPRSS2. […] ACE2 could be a species-specific barrier that interferes with bat-to-human coronavirus cross-species transmission. […] To investigate bats and pangolin as hosts in SARS-CoV-2 cross-species transmission, we perform an evolutionary analysis combining viral and host phylogenies and divergence of ACE2 and TMPRSS2 amino acid sequences between CoV hosts. […] In contrast to TMPRSS2, pangolin ACE2 amino acid sequence has low evolutionary divergence compared with humans and is more divergent from bats. […] Comparing SARS-CoV with SARS-CoV-2 origins, pangolin has yet lower ACE2 evolutionary divergence with humans than civet-the main intermediary host of SARS-CoV.
32592145 A critical step in the crosstalk between the virus and the host cell is the binding of SARS-CoV-2 spike protein to the angiotensin-converting enzyme 2 (ACE2) receptor present on the surface of the host cells. […] We have designed a novel peptide that could inhibit SARS-CoV-2 spike protein interaction with ACE2, thereby blocking the cellular entry of the virus.
32592657 However, statins may increase the risk of SARS-CoV-2 viral entry by inducing ACE2 expression.
32593613 In silico modelling has identified several natural products including quercetin as potential highly effective disruptors of the initial infection process involving binding to the interface between the SARS-CoV-2 (Covid-19) Viral Spike Protein and the epithelial cell Angiotensin Converting Enzyme-2 (ACE2) protein.
32593740 Obesity patients are more susceptible to develop COVID-19 severe outcome due to the role of angiotensin-converting enzyme 2 (ACE2) in the viral infection. […] ACE2 is regulated in the human cells by different genes associated with increased (TLR3, HAT1, HDAC2, KDM5B, SIRT1, RAB1A, FURIN and ADAM10) or decreased (TRIB3) virus replication. […] Our results, in human subcutaneous adipocytes cell culture, indicate a positive effect of irisin on the expression of multiple genes related to viral infection by SARS-CoV-2; furthermore, translatable for other tissues and organs targeted by the novel coronavirus and present, thus, promising approaches for the treatment of COVID-19 infection as therapeutic strategy to decrease ACE2 regulatory genes.
32594472 SARS-coronavirus 2 (SARS-CoV-2) enters the host-cells by binding the transmembraneous angiotensin converting enzyme 2 (ACE2) when causing coronavirus disease 2019 (COVID-19).
32594572 Herein, we performed a comprehensive review of literatures (from inception to 30 May 2020) using PubMed, CNKI, medRxiv and bioRxiv with the terms “((novel coronavirus) OR (2019 novel coronavirus) OR (2019-nCoV) OR (Coronavirus disease 2019) OR (COVID-19) OR (SARS-CoV-2)) AND ((Dermatology) OR (skin) OR (rash) OR (cutaneous))” and “((ACE2) OR (Angiotensin-converting enzyme)) AND ((skin) OR (epidermis) OR (dermis)).” […] The receptor of SARS-CoV-2, ACE2, was found to be expressed on skin, mainly on keratinocytes. […] Our review systematically presented the clinical characteristics of 507 patients and showed that skin might be the potential target of the infection according to ACE2 expression.
32594644 Angiotensin converting enzyme 2(ACE2) is the cellular receptor for SARS-CoV-2. […] The mRNA expression of ACE2 was expressed in both germ cells and somatic cells. […] Moreover, the positive rate of ACE2 in testes of infertile men was higher than normal, which indicates that SARS-CoV-2 may cause reproductive disorders through pathway activated by ACE2 and the men with reproductive disorder may easily to be infected by SARS-CoV-2. […] The expression level of ACE2 was related to the age, and the mid-aged with higher positive rate than young men testicular cells.
32595357 Current neutralizing antibody development studies primarily target the S protein among the structural elements of SARS-CoV-2, which mediates the cell entry of the virus through the angiotensin converting enzyme 2 (ACE2) receptor of host cells.
32595762 These features may be attributable to the following facts: (a) COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and its receptor angiotensin converting enzyme 2 (ACE2) was found to be highly expressed in GI epithelial cells, providing a prerequisite for SARS-CoV-2 infection; (b) SARS-CoV-2 viral RNA has been found in stool specimens of infected patients, and 20% of patients showed prolonged presence of SARS-CoV-2 RNA in faecal samples after the virus converting to negative in the respiratory system.
32596078 Although multiple drugs show promise in the treatment of COVID-19 via either inhibiting viral replication or preventing fusion of the virus to the ACE2 receptors, further investigation is still warranted and necessary before the admission of any type of pharmaceutical agent.
32598305 It has been now clearly established that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing COVID-19, infects the host cell through biding and being internalized with angiotensin converting enzyme 2 (ACE2), a surface protein expressed in a noticeable number of human cells, especially in those of upper and lower respiratory tracts, heart, kidney, testis, adipose tissue, gastrointestinal system and in lymphocytes. […] Accumulating evidence now suggests that genetic polymorphisms in the ACE2 gene may modulate intermolecular interactions with the spike protein of SARS-CoV-2 and/or contribute to pulmonary and systemic injury by fostering vasoconstriction, inflammation, oxidation and fibrosis. […] We hence argue that the development of genetic tests aimed at specifically identifying specific COVID-19-susceptible or -protective ACE2 variants in the general population may be a reasonable strategy for stratifying the risk of infection and/or unfavorable disease progression.
32599304 Furthermore, although a study found the ACE2 receptor, used by SARS-CoV-2, widely distributed in specific cell types of the maternal-fetal interface, there is no evidence of vertical transmission for any of the coronaviruses.
32600166 The possible reasons for the very low COVID-19 infection in asthma patients in China may be as follows: the expression of ACE2 in asthma patients is relatively low; the use of ICS in asthma patients may have protective effect; data bias and ethnic differences are also possible reasons, too.
32600476 It is explained how sex can affect angiotensin converting enzyme-2 (ACE2), that is a key component for the pathogenesis of COVID-19, and summarized the gender differences in immune responses and how sex hormones are involved in immune processes.
32601125 Indeed, the COVID-19 virus binds to angiotensin-converting enzyme type 2 (ACE2), which is expressed in endothelial cells. […] ACE2 could be implicated in the production of reactive oxygen species (ROS) caused by endothelial dysfunction due to viral damage.
32602046 They also expressed angiotensin-converting enzyme 2 (ACE2), a receptor for SARS-CoV and SARS-CoV-2. […] In contrast, cancer cell line did not express endogenous SLC34A3, cubilin and ACE2. […] Very interestingly, ACE2 expression was around twofold higher in 3D organoids culture compared to that in 2D CR culture condition.
32602627 Both SARS-CoV-2 and SARS-CoV enter human cells via the interactions between viral crown-like spike protein and human angiotensin-converting enzyme 2 (ACE2) receptor. […] Here, we aim to review the involvement of ACE2 in human CoV infections by discussing the roles of ACE2 in CoV evolution, cross-species transmissibility, and COVID-19 susceptibility.
32602823 Like SARS-CoV, some bat SL-CoVs, such as WIV1, also use angiotensin converting enzyme 2 (ACE2) from human and bat as entry receptor. […] However, whether these viruses can also use the ACE2 of other animal species as their receptor remains to be determined. […] We report herein that WIV1 has a broader tropism to ACE2 orthologs than SARS-CoV isolate Tor2. […] Among the 9 ACE2 orthologs examined, human ACE2 exhibited the highest efficiency to mediate the infection of WIV1 pseudotyped virus.
32603424 A critical interaction between SARS-CoV-2 and the angiotensin-converting enzyme 2 (ACE2) facilitates viral entry into the host cell. […] ACE2 is expressed in pancreatic islets, vascular endothelium, and adipose tissue, and the SARS-CoV-2 -ACE2 interaction in these tissues, along with other factors, governs the spectrum and the severity of clinical manifestations among COVID-19 patients with metabolic syndrome.
32606886 These include the different levels of the ubiquitously present human angiotensin I converting enzyme 2 (ACE2) receptors gene expression and its variant alleles, the different binding affinities of ACE2 to the virus spike (S) protein given its L- and S-subtypes and the subsequent extent of innate immunity-related hypercytokinemia.
32607393 Developing an ACE2 inhibitor could be a possible therapeutic target.
32611305 Also, ACE1 and angiotensin receptor blockers (ARB) may stimulate ACE2 expression and worse the prognosis. […] Intravenous infusions of ACEIs and ARBs in experimental animals increase the numbers of ACE2 receptors.
32611313 This pocket is found at the inter-chain interface that exists between two domains prior to the virion binding to human Angiotensin Converting Enzyme 2 (ACE2) protein. […] One of these domains is the highly mobile receptor binding domain, which must move into position to interact with ACE2, which is an essential feature for viral entry to the host cell.
32613681 Experimentally, vitamin D increases the ratio of angiotensin-converting enzyme 2 (ACE2) to ACE, thus increasing angiotensin II hydrolysis and reducing subsequent inflammatory cytokine response to pathogens and lung injury.
32613971 The antibodies also effectively suppressed SARS-CoV-2 RBD binding to soluble ACE2, indicating that RBD-mFc may be further developed as a safe and effective SARS-CoV-2 vaccine.
32617987 Understanding the variations in angiotensin-converting enzyme 2 (ACE2) and human leukocyte antigen (HLA) that may affect the severity of 2019-nCoV infection could help in identifying individuals at a higher risk from the COVID-19.
32620366 The aim of this brief communication is to describe the pathophysiology of this sex-discrepancy, based on the infectivity mechanism of the coronavirus including the Angiotensin-Converting Enzyme 2 (ACE2), the Type II transmembrane Serine Protease (TMPRSS2), and the androgen receptor.
32620513 In addition, the placenta has been shown to possess ACE2 receptors on the villous cytotrophoblast and the syncytiotrophoblast and findings suggest that the coronavirus enters the host cells via these ACE2 receptors. […] Both normal pregnancy and COVID-19 are marked by decreased lymphocytes, NKG2A inhibitory receptors, and increased ACE2, IL-8, IL-10, and IP-10 it therefore safer to conclude that pregnancy is a risk factor for COVID-19 development. […] Furthermore, the presence of the ACE2 receptors in the placenta may increase the risk of mother to baby transmission of the virus.
32622411 Identification of cell types coexpressing the key angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) genes and proteins as well as other candidates potentially involved in SARS-CoV-2 cell entry. […] On the basis of single-cell RNA sequencing data, coexpression of ACE2 and TMPRSS2 was not detected in testicular cells, including sperm. […] A subpopulation of oocytes in nonhuman primate ovarian tissue was found to express ACE2 and TMPRSS2, but coexpression was not observed in ovarian somatic cells. […] There was general agreement between publicly available bulk RNA and protein datasets in terms of ACE2 and TMPRSS2 expression patterns in testis, ovary, endometrial, and placental cells.
32623038 In addition, angiotensin-converting enzyme 2 (ACE2) is a receptor for SARS-CoV-2 in the human body.
32623480 With this aim, we performed an in silico comparative modeling analysis, which allows gaining new insights into the main conformational changes occurring in the SARS-CoV-2 spike protein, at the level of the receptor-binding domain (RBD), along interactions with human cells angiotensin-converting enzyme 2 (ACE2) receptor, that favor human cell invasion. […] Furthermore, our analysis provides (1) an ideal pipeline to identify already characterized antibodies that might target SARS-CoV-2 spike RBD, aiming to prevent interactions with the human ACE2, and (2) instructions for building new possible neutralizing antibodies, according to chemical/physical space restraints and complementary determining regions (CDR) mutagenesis of the identified existing antibodies. […] The proposed antibodies show in silico high affinity for SARS-CoV-2 spike RBD and can be used as reference antibodies also for building new high-affinity antibodies against present and future coronaviruses able to invade human cells through interactions of their spike proteins with the human ACE2. […] More in general, our analysis provides indications for the set-up of the right biological molecular context for investigating spike RBD-ACE2 interactions for the development of new vaccines, diagnostic kits, and other treatments based on the targeting of SARS-CoV-2 spike protein.
32623546 Like the severe acute respiratory syndrome coronavirus (SARS-CoV), this novel type of coronavirus, SARS-CoV-2, has been demonstrated to utilize angiotensin-converting enzyme 2 (ACE2) as an entry point to the cells. […] Using human pluripotent stem cells-derived neurons, here we show the expression of ACE2 in human neurons via immunocytochemistry.
32624360 Cellular angiotensin-converting enzyme 2 (ACE2) is the receptor of SARS-CoV-2 which is identical or similar in different species of animals such as pigs, ferrets, cats, orangutans, monkeys, and humans.
32625165 Considering the tropism of SARS-CoV-2, ACE2, is prevailing in CNS, and the neuro-invasive property of human coronavirus was widely reported, there is a need to identified the possible complications during COVID-19 for CNS.
32626626 The novel coronaviruses causing severe acute respiratory syndrome (SARS) and coronavirus disease 2019 (COVID-19) have been shown to utilize angiotensin-converting enzyme 2 (ACE2) as the receptor for entry into the host cells. […] The two enzymes of RAS, angiotensin-converting enzyme (ACE) and ACE2, serve a contrasting function. […] ACE helps in the formation of angiotensin II (AGII) from angiotensin I (AGI), and ACE2 cleaves AGI and AGII into AG (1-9) and AG (1-7) respectively. […] The ACE-induced AGII has vasoconstrictor and pro-inflammatory properties via AT1R, whereas ACE2 has been shown to protect against lung injury. […] A review of articles searched in PubMed and peer-reviewed journals of importance was done using search terms “ACE2,” “AT2,” “SARS,” and COVID-19." […] Animal studies have shown that ACE2 and AT2 receptors counter the pro-inflammatory and other effects mediated by angiotensin II by their vasodilator, anti-inflammatory, anti-fibrotic, and anti-proliferative effects. […] The instrumental role of recombinant ACE2, AT2 receptor agonists, and AT1 receptor blockers may be helpful in the treatment of COVID-19.
32627059 Our hypothesis was that intestinal SARS-CoV-2 receptor ACE2 expression depends on patients’ age. […] ACE2 gene expression was directly correlated with age (Spearman’s r = 0.317, p = 0.039). […] With each year, duodenal ACE2 expression increased by 0.083 RU. […] The higher intestinal ACE2 mRNA expression in older patients may impact on their susceptibility to develop intestinal symptoms.
32627524 Spike protein (S protein) is the virus “key” to infect cells and is able to strongly bind to the human angiotensin-converting enzyme2 (ACE2), as has been reported. […] Analysis the S protein binding to the host ACE2 receptor showed a 30% higher binding energy for SARS-CoV-2 than for the SARS-CoV S protein.
32628899 For the etiologic agent of COVID-19 (SARS-CoV-2), a receptor has been identified as angiotensin-converting enzyme-2 (ACE2). […] ACE2 modulates the intracellular signaling generated by integrins.
32628976 For this reason, we investigated the involvement of genetic factors associated with SARS-CoV-2 infection with a focus on angiotensin-converting enzyme (ACE)-related genes, because ACE2 is a receptor for SARS-CoV-2.
32629204 The disease is caused by a very small virus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is an enveloped single-stranded RNA virus with a spike-like structure on its envelope that can interact with the angiotensin-converting enzyme 2 (ACE2) receptor after cleavage. […] ACE2 receptors are present in the human lungs and other organs.
32629518 Angiotensin converting enzyme 2 (ACE2) has been identified as a key host factor, required for virus entry into cells. […] Interestingly, ACE2 is expressed not only in the respiratory system, but also in the other organs and systems including adrenal glands.
32629817 By attaching to the angiotensin converting enzyme 2 (ACE2) protein on lung and intestinal cells, Sudden Acute Respiratory Syndrome (SARS-CoV-2) can cause respiratory and homeostatic difficulties leading to sepsis.
32629875 Angiotensin converting enzyme 2 (ACE2), the receptor for SARS-CoV-2 and other coronaviruses, is a transmembrane protein expressed by lung alveolar epithelial cells, enterocytes, and vascular endothelial cells, whose physiologic role is to induce the maturation of angiotensin I to generate angiotensin 1-7, a peptide hormone that controls vasoconstriction and blood pressure.
32632717 To seek potential Chinese herbal medicine (CHM) for the treatment of coronavirus disease 2019 (COVID-19) through the molecular docking of the medicine with SARS-CoV-2 3CL hydrolytic enzyme and the angiotensin converting enzyme II(ACE2) as receptors, using computer virtual screening technique, so as to provide a basis for combination forecasting. […] The molecular docking of CHM with the SARS-Cov-2 3CL hydrolase and the ACE2 converting enzyme, which were taken as the targets, was achieved by the Autodock Vina software. […] The CHM monomers acting on 3CLpro and ACE2 receptors were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, the active ingredients were selected, and the key CHMs and compounds were speculated. […] The core drug pair of Forsythiae Fructus-Lonicerae Japonicae Flos containing multiple components and targets is easy to combine with 3CLpro and ACE2, and exerts an anti-COVID-19 pneumonia effect through multi-component and multi-target, and plays the role of anti-COVID-19 pneumonia in multi-pathway.
32633235 However, despite the theoretical concerns of possible increased ACE2 expression by RAS blockade, there is no evidence that RAS inhibitors are harmful during COVID-19 infection, and indeed they have been shown to be beneficial in some animal studies.
32633236 Moreover, viral receptor angiotensin converting enzyme 2 (ACE2) is highly expressed in the gastrointestinal tract and enables the invasion of the gastrointestinal epithelium as demonstrated in vitro and in vivo.
32633718 The entry point for the virus is ACE2, which is a component of the counteracting hypotensive axis of RAS. […] Bradykinin is a potent part of the vasopressor system that induces hypotension and vasodilation and is degraded by ACE and enhanced by the angiotensin1-9 produced by ACE2. […] Comparison with BALF from controls identifies a critical imbalance in RAS represented by decreased expression of ACE in combination with increases in ACE2, renin, angiotensin, key RAS receptors, kinogen and many kallikrein enzymes that activate it, and both bradykinin receptors.
32633728 The pathophysiology of ICH patients with SARS-CoV-2 infection includes viral invasion, dysfunction of the ACE2-Ang (1-7)-MasR and ACE-Ang II-AT1R axes, overactive immune response, cytokine storm, and excessive oxidative stress.
32633815 The alignments of RBD contact residues to ACE2 justified?
32634813 This patient had ischemic injuries in different sites as well as venous thrombosis; hence, we speculate that Sars Cov2 could have a direct role in promoting vascular accidents since its receptor ACE2 is a surface protein also expressed by endothelial cells.
32635188 Angiotensin-converting enzyme 2 (ACE2) has been recognized as the entry receptor of the novel severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). […] Structural and sequence variants in ACE2 gene may affect its expression in different tissues and determine a differential response to SARS-Cov-2 infection and the COVID-19-related phenotype. […] The present study investigated the genetic variability of ACE2 in terms of single nucleotide variants (SNVs), copy number variations (CNVs), and expression quantitative loci (eQTLs) in a cohort of 268 individuals representative of the general Italian population. […] The eQTLs analysis located in and targeting ACE2 revealed a high distribution of eQTL variants in different brain tissues, suggesting a possible link between ACE2 genetic variability and the neurological complications in patients with COVID-19. […] Further research is needed to clarify the possible relationship between ACE2 expression and the susceptibility to neurological complications in patients with COVID-19.
32635289 Angiotensin converting enzyme 2 (ACE2) is the recognized host cell receptor responsiblefor mediating infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). […] ACE2bound to tissue facilitates infectivity of SARS-CoV-2; thus, one could argue that decreasing ACE2tissue expression would be beneficial. […] However, ACE2 catalytic activity towards angiotensin I (AngI) and II (Ang II) mitigates deleterious effects associated with activation of the renin-angiotensinaldosteronesystem (RAAS) on several organs, including a pro-inflammatory status. […] At the tissuelevel, SARS-CoV-2 (a) binds to ACE2, leading to its internalization, and (b) favors ACE2 cleavage toform soluble ACE2: these actions result in decreased ACE2 tissue levels. […] Preserving tissue ACE2activity while preventing ACE2 shredding is expected to circumvent unrestrained inflammatoryresponse. […] Concerns have been raised around RAAS modulators and their effects on ACE2expression or catalytic activity. […] However, recent data from observational and meta-analysis studies in SARS-CoV-2-infected patients have concluded that RAAS modulators do not increase plasma ACE2 levels orsusceptibility to infection and are not associated with more severe diseases. […] This review presentsour current but evolving knowledge of the complex interplay between SARS-CoV-2 infection, ACE2levels, modulators of RAAS activity and the effects of RAAS modulators on ACE2 expression.
32635302 The lungs are often damaged due to the presence of Sars-CoV-2 binding receptor ACE2 on epithelial alveolar cells.
32636754 The virus uses its spike glycoprotein receptor-binding domain to interact with host cell angiotensin-converting enzyme 2 (ACE2) sites to initiate a cascade of events that culminate in severe acute respiratory syndrome in some individuals.
32638018 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly binds to ACE2 (angiotensin-converting enzyme 2) to facilitate cellular entry. […] Compared with the lung or respiratory tract, the human heart exhibits greater ACE2 expression. […] This study aims to analyse ACE2 and SARS-CoV-2 spike (S) protein proteases at the single-cell level, to explore the cardiac involvement in COVID-19 and improve our understanding of the potential cardiovascular implications of COVID-19. […] With public single-cell sequence data analysis, ACE2 expression in the adult human heart is higher than that in the lung (adjusted P < 0.0001). […] Compared with the lung, ACE2 is relatively more highly expressed in the human heart, while the key S protein priming protease, TMPRSS2, is rarely expressed. […] The low percentage of ACE2+/TMPRSS2+ cells reduced heart vulnerability to SARS-CoV-2 to some degree.
32638221 Additionally, the receptor by which the virus gains cellular entry, ACE2, has been found to be expressed in different human body systems, thereby potentiating its infection in those locations.
32639084 Since the expression profile of ACE2, a crucial cell entry receptor for SARS-CoV-2, could indicate the susceptibility to SARS-CoV-2 infection, here we systematically dissected ACE2 expression using large-scale multi-omics data from 30 organs/tissues, 33 cancer types and some common chronic diseases involving >28 000 samples. […] Strikingly, ACE2 was up-regulated in cervical squamous cell carcinoma and endocervical adenocarcinoma, colon adenocarcinoma, oesophageal carcinoma, kidney renal papillary cell carcinoma, lung adenocarcinoma and uterine corpus endometrial carcinoma compared to controls. […] Furthermore, the patients with common chronic diseases regarding angiocardiopathy, type 2 diabetes, liver, pneumonia and hypertension were also with higher ACE2 expression compared to related controls, which were validated using independent data sets. […] Collectively, our study may reveal a novel important mechanism that the patients with certain cancers and chronic diseases may express higher ACE2 expression compared to the individuals without diseases, which could lead to their higher susceptibility to multi-organ injury of SARS-CoV-2 infection.
32639848 As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects the human body through the combination of angiotensin-converting enzyme 2 (ACE2) in the gastrointestinal tract, the mechanism underlying the gastrointestinal symptoms may involve damage to the intestinal mucosal barrier and promotion of the production of inflammatory factors.
32639866 The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of pneumocytes, the hallmark of the pandemic coronavirus disease 2019 (COVID-19) involving both alveolar interstitium and capillaries, is linked to angiotensin-converting enzyme 2 (ACE2) binding and its functional downregulation. […] ACE2 is a key enzyme for the balance between the two main arms of the RAS: the ACE/angiotensin (Ang) II/Ang II type 1 receptor axis (“classic RAS”) and the ACE2/Ang(1-7)/Mas receptor (MasR) axis (“anti-RAS”). […] The ACE2 downregulation, as a result of SARS-coronaviruses binding, enhances the classic RAS, leading to lung damage and inflammation with leaky pulmonary blood vessels and fibrosis, when the attenuation mediated by the anti-RAS arm is reduced.
32640417 The extracted literatures are scrutinized by the authors. 58 literatures including original articles, case reports and case series were selected by the authors to analyze the differential distribution of neurological impairments in COVID-19 positive patients along with angiotensin-converting enzyme-2 (ACE2) expression dynamics in neuronal and non-neuronal tissue in CNS and PNS with neuroinvasive potential of SARS-CoV2.
32641214 Gene expression was high for TMPRSS4, CTSL, CTSB, FURIN, MX1, and BSG; medium for TMPRSS2; and low for ACE2. […] ACE2, TMPRSS4, CTSB, CTSL, and MX1 expression increased toward the window of implantation. […] TMPRSS4 expression was positively correlated with ACE2, CTSB, CTSL, MX1, and FURIN during several cycle phases; TMPRSS2 was not statistically significantly altered across the cycle. […] ACE2, TMPRSS4, CTSB, CTSL, BSG, and MX1 expression increased with age, especially in early phases of the cycle. […] Endometrial tissue is likely safe from SARS-CoV-2 cell entry based on ACE2 and TMPRSS2 expression, but susceptibility increases with age.
32642005 One potential therapeutic target is angiotensin converting enzyme 2 (ACE2). […] ACE2 primarily catalyzes the conversion of angiotensin I (Ang I) to a nonapeptide angiotensin or the conversion of angiotensin II (Ang II) to angiotensin 1-7 (Ang 1-7) and has direct effects on cardiac function and multiple organs via counter-regulation of the renin-angiotensin system (RAS). […] Significant to COVID-19, ACE2 is postulated to serve as a major entry receptor for SARS-CoV-2 in human cells, as it does for SARS-CoV. […] ACE2 is expressed by epithelial cells of the lungs at high level, a major target of the disease, as seen in post-mortem lung tissue of patients who died with COVID-19, which reveals diffuse alveolar damage with cellular fibromyxoid exudates bilaterally. […] Comparatively, ACE2 is expressed at low level by vascular endothelial cells of the heart and kidney but may also be targeted by the virus in severe COVID-19 cases. […] Interestingly, SARS-CoV-2 infection downregulates ACE2 expression, which may also play a critical pathogenic role in COVID-19. […] Importantly, targeting ACE2/Ang 1-7 axis and blocking ACE2 interaction with the S protein of SARS-CoV-2 to curtail SARS-CoV-2 infection are becoming very attractive therapeutics potential for treatment and prevention of COVID-19. […] Here, we will discuss the following subtopics: 1) ACE2 as a receptor of SARS-CoV-2; 2) clinical and pathological features of COVID-19; 3) role of ACE2 in the infection and pathogenesis of SARS; 4) potential pathogenic role of ACE2 in COVID-19; 5) animal models for pathological studies and therapeutics; and 6) therapeutics development for COVID-19.
32643448 The main active compounds of HSBDF were docked with SARS-CoV-2 and angiotensin converting enzyme II (ACE2). […] The results of molecular docking showed that baicalein and quercetin were the top two compounds of HSBDF, which had high affinity with ACE2. […] Baicalein and quercetin in HSBDF may regulate multiple signaling pathways through ACE2, which might play a therapeutic role on COVID-19.
32643603 Here, we overcome this difficulty by exogenous delivery of human ACE2 with a replication-deficient adenovirus (Ad5-hACE2). […] Ad5-hACE2-sensitized mice developed pneumonia characterized by weight loss, severe pulmonary pathology, and high-titer virus replication in lungs. […] Ad5-hACE2-transduced mice enabled rapid assessments of a vaccine candidate, of human convalescent plasma, and of two antiviral therapies (poly I:C and remdesivir).
32645228 SARS-CoV-2, the pathogen of COVID-19, enters into cells through binding to the Angiotensin Converting Enzyme (ACE) homolog-2 (ACE2). […] ACE2 is a regulator of two contrary pathways in renin angiotensin system (RAS): ACE-Ang-II-AT1R axis and ACE2-Ang 1-7-Mas axis. […] Viral entry process eventuate in downregulation of ACE2 and subsequent activation of ACE-Ang-II-AT1R axis. […] The link between obesity and severe COVID-19 may be attributed to ACE2 consumption and subsequent ACE-Ang-II-AT1R axis activation. […] Therefore, patients with SARS-CoV-2 infection may benefit from therapeutic strategies that activate ACE2-Ang 1-7-Mas axis, such as Ang II reseptor blockers (ARBs), ACE inhibitors (ACEIs), Mas receptor agonists and ACE2.
32645326 Moreover, a 3.4 Å cryo-electron microscopy (cryo-EM) structure of a neutralizing monoclonal Fab-spike complex revealed an epitope that blocks ACE2 receptor binding.
32645344 The spike (S) glycoprotein of betacoronavirus SARS-CoV-2 is a homotrimeric class I fusion protein that exists in a metastable conformation for cleavage by host cell proteases furin and TMPRSS2, thereby undergoing substantial structural rearrangement for ACE2 host cell receptor binding and subsequent viral entry by membrane fusion.
32645632 Recently, a cell surface protein, known as angiotensin-converting enzyme II (ACE2), has been identified to be involved in receptor-mediated endocytosis for SARS-CoV-2 entry to the cells. […] Baricitinib is expected to interrupt the passage and intracellular assembly of SARS-CoV-2 into the target cells mediated by ACE2 receptor, and treat cytokine storm caused by COVID-19.
32645974 Reports of emerging cardiovascular complications due to its clinical prescription are revealing the crucial role of angiotensin-converting enzyme 2 (ACE2), which serves as a target receptor for SARS-CoV-2. […] While starting with the crucial role of ACE2, we here discuss the impact of HCQ on systemic cardiovascular function, its associated risks, and the scope of HCQ-based regimes in current clinical settings. […] Taken together, this review provides crucial insights into the role of ACE2 in SARS-CoV-2-led cardiovascular activity, and concurrently assesses the efficacy of HCQ in contemporary clinical settings.
32647346 We also biochemically characterized their relative stabilities and affinities for the SARS-CoV-2 receptor ACE2. […] These observations suggest that cleavage at the furin-cleavage site decreases the overall stability of SARS-CoV-2 S and facilitates the adoption of the open conformation that is required for S to bind to the ACE2 receptor.
32649962 Intriguingly the receptor for SARS-CoV-2 is ACE2, a member of the angiotensin receptor family that has a relatively large tissue distribution. […] The adipose tissue also expresses ACE2, suggesting that adipocytes are potentially infected by SARS-CoV-2.
32650788 The viral spike glycoprotein is very likely to interact with host Angiotensin-Converting Enzyme 2 (ACE2) and transmits its genetic materials and hijacks host machinery with extreme fidelity for self propagation. […] Few attempts have been made to develop a suitable vaccine or ACE2 blocker or virus-receptor inhibitor within this short period of time.
32651579 Given that ACE2, the entry receptor for the causative coronavirus SARS-CoV-2, is expressed in multiple extrapulmonary tissues, direct viral tissue damage is a plausible mechanism of injury. […] In addition, endothelial damage and thromboinflammation, dysregulation of immune responses, and maladaptation of ACE2-related pathways might all contribute to these extrapulmonary manifestations of COVID-19.
32651761 The variations in sequence homology of ACE2 receptor across species is identified as one of the factors determining virulence and pathogenicity in animals.
32651900 Among the discrete data available, an important finding is that angiotensin converting enzymes 2 (ACE2) receptor, that aids the SARS-CoV-2 entry into host cells, is profoundly expressed in testicular cells. […] In addition, the endogenous androgen milieu and its receptors are associated with ACE2 activation reflecting that enhanced testosterone levels may trigger the pathogenesis of COVID-19.
32652001 It is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a coronavirus that uses angiotensin-converting enzyme 2 (ACE2) as an entry point to the cells. […] ACE2 is a transmembrane carboxypeptidase and member of the renin-angiotensin system. […] This mini-review summarizes the main findings regarding ACE2 expression and function in endocrine tissues. […] We discuss rapidly evolving knowledge on the potential role of ACE2 and SARS coronaviruses in endocrinology and the development of diabetes mellitus, hypogonadism, and pituitary and thyroid diseases.
32653522 The review aims to grab the attention of the researchers all over the globe, towards the role of ACE2 in COVID-19 disease. […] ACE2 serves as a molecular target for the SARS-CoV-2, to enter the target cell, by interacting with the viral glycoprotein spikes. […] However, the complexity began when numerous studies identified the protective response of ACE2 in abbreviating the harmful effects of vasoconstrictor, anti-inflammatory peptide, angiotensin 2, by mediating its conversion to angiotensin-(1-7), which exercised antagonistic actions to angiotensin 2. […] Furthermore, certain investigations revealed greater resistance among children as compared to the geriatrics, towards COVID-19 infection, despite the elevated expression of ACE2 in pediatric population. […] Based upon such evidences, the review demonstrated possible therapeutic interventions, targeting both the protective and deleterious effects of ACE2 in COVID-19 disease, primarily inhibiting ACE2-virus interactions or administering soluble ACE2.
32653530 The use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor type 1 blockers (ARBs) improve CVD outcomes; however, there is concern that they may worsen the prognosis of CVD patients that become infected with SARS-CoV-2 because the virus uses the ACE2 receptor to bind to and subsequently infect host cells.
32654557 The severe acute respiratory syndrome coronavirus 2 is known to infect host cells by interacting with ACE2 (angiotensin-converting enzyme 2) expressed in the respiratory epithelium. […] There have been concerns on whether alterations of ACE2 expression by renin-angiotensin-aldosterone system (RAAS) inhibitors would contribute to the infectivity and severity of coronavirus disease 2019 (COVID-19).
32655489 SARS-CoV-2 may reach ACE2 receptors on neuronal tissue through mode of the general circulation.
32656311 Docking results suggest that curcumin and nimbin exhibits highest interaction with spike glycoprotein (MolDock score - 141.36 and - 148.621 kcal/mole) and ACE2 receptor (MolDock score - 142.647 and - 140.108 kcal/mole) as compared with other selected natural products/drugs and controls. […] Our study exhibited that curcumin, nimbin, withaferin A, piperine, mangiferin, thebaine, berberine, and andrographolide have significant binding affinity towards spike glycoprotein of SARS-CoV-2 and ACE2 receptor and may be useful as a therapeutic and/or prophylactic agent for restricting viral attachment to the host cells. […] However, few other natural products like resveratrol, quercetin, luteolin, naringenin, zingiberene, and gallic acid has the significant binding affinity towards ACE2 receptor only and therefore may be used for ACE2-mediated attachment inhibition of SARS-CoV-2.
32656452 The angiotensin-converting enzyme 2 (ACE2) is the functional receptor for SARS-CoV and SARS-CoV-2 to enter the host cells. […] In particular, the interaction of viral spike proteins with ACE2 is a critical step in the viral replication cycle. […] The receptor-binding domain of the viral spike proteins and ACE2 have several cysteine residues. […] In this study, the role of thiol-disulfide balance on the interactions between SARS-CoV/CoV-2 spike proteins and ACE2 was investigated using molecular dynamics simulations. […] The study revealed that the binding affinity was significantly impaired when all of the disulfide bonds of both ACE2 and SARS-CoV/CoV-2 spike proteins were reduced to thiol groups.
32657473 We found that an important regulatory factor angiotensin-converting enzyme 2 (ACE2) may be involved in host pathological changes on binding to the coronavirus after infection. […] On triggering functional changes in ACE2/AT2R, the cytokine homeostasis regulation axis becomes imbalanced via the Renin-Angiotensin System and IP-10, leading to a cytokine storm.
32658736 This may be important for infection and the ability of the virus to locate ACE2 as its known main host cell surface receptor, and if so it becomes a pharmaceutical target. […] It might even open up the possibility of an alternative receptor to ACE2.
32660065 Angiotensin-converting enzyme 2 (ACE2) is expressed in human vascular endothelium, respiratory epithelium, and other cell types, and is thought to be a primary mechanism of SARS-CoV-2 entry and infection. […] In physiological condition, ACE2 via its carboxypeptidase activity generates angiotensin fragments (Ang 1-9 and Ang 1-7), and plays an essential role in the renin-angiotensin system (RAS), which is a critical regulator of cardiovascular homeostasis. […] SARS-CoV-2 via its surface spike glycoprotein interacts with ACE2 and invades the host cells. […] Here we reviewed the molecular basis of SARS-CoV-2 infection, the roles of ACE2, RAS signaling, and a possible link between the pre-existing endothelial dysfunction and SARS-CoV-2 induced endothelial injury in COVID-19 associated mortality.
32660186 Studies have shown that SARS-CoV-2 infects the human body and replicates effectively through angiotensin-converting enzyme II (ACE2). […] ACE2 is widely distributed in various tissues and organs of the human body, such as intestinal epithelial cells, cardiomyocytes, renal tubular epithelial cells, and testicular stromal cells, etc.
32660650 Both SARS-CoV-2 and SARS-CoV enter host cells via the angiotensin-converting enzyme 2 (ACE2) receptor, which is expressed in various human organs. […] ACE2 catalyzes angiotensin II conversion to angiotensin-(1-7), and the ACE2/angiotensin-(1-7)/MAS axis counteracts the negative effects of the renin-angiotensin system (RAS), which plays important roles in maintaining the physiological and pathophysiological balance of the body. […] In addition to the direct viral effects and inflammatory and immune factors associated with COVID-19 pathogenesis, ACE2 downregulation and the imbalance between the RAS and ACE2/angiotensin-(1-7)/MAS after infection may also contribute to multiple organ injury in COVID-19. […] The SARS-CoV-2 spike glycoprotein, which binds to ACE2, is a potential target for developing specific drugs, antibodies, and vaccines. […] Restoring the balance between the RAS and ACE2/angiotensin-(1-7)/MAS may help attenuate organ injuries. […] SARS-CoV-2 enters lung cells via the ACE2 receptor. […] The cell-free and macrophage-phagocytosed virus can spread to other organs and infect ACE2-expressing cells at local sites, causing multi-organ injury.
32661058 Co-crystal structures of two IGHV3-53-neutralizing antibodies with RBD, with or without Fab CR3022, at 2.33- to 3.20-angstrom resolution revealed that the germline-encoded residues dominate recognition of the angiotensin I converting enzyme 2 (ACE2)-binding site.
32661139 SARS-CoV-2 uses human angiotensin-converting enzyme 2 (ACE2) as its receptor to infect cells. […] In an effort to search for the potential intermediate or amplifying animal hosts of SARS-CoV-2, we examined receptor activity of ACE2 from 14 mammal species and found that ACE2s from multiple species can support the infectious entry of lentiviral particles pseudotyped with the wild-type or furin cleavage site-deficient S protein of SARS-CoV-2. […] ACE2 of human/rhesus monkey and rat/mouse exhibited the highest and lowest receptor activities, respectively. […] Among the remaining species, ACE2s from rabbit and pangolin strongly bound to the S1 subunit of SARS-CoV-2 S protein and efficiently supported the pseudotyped virus infection. […] These findings have important implications for understanding potential natural reservoirs, zoonotic transmission, human-to-animal transmission, and use of animal models.IMPORTANCE SARS-CoV-2 uses human ACE2 as a primary receptor for host cell entry. […] Viral entry mediated by the interaction of ACE2 with spike protein largely determines host range and is the major constraint to interspecies transmission. […] We examined the receptor activity of 14 ACE2 orthologs and found that wild-type and mutant SARS-CoV-2 lacking the furin cleavage site in S protein could utilize ACE2 from a broad range of animal species to enter host cells.
32661206 Cellular receptor ACE2, serine protease TMPRSS2 and exopeptidase CD26 (also known as DPP4) are the three membrane bound proteins potentially implicated in SARS-CoV-2 infection.
32661393 S localizes on the virion surface and mediates recognition of cellular receptor angiotensin-converting enzyme 2 (ACE2)4-6. […] Eliciting neutralizing antibodies that block S-ACE2 interaction7-9, or indirectly prevent membrane fusion10, constitute an attractive modality for vaccine-elicited protection11.
32661423 The SARS-CoV-2 receptor binding domain (RBD) of the spike protein binds to the human angiotensin-converting enzyme 2 (ACE2) receptor as a prelude to viral entry into the cell. […] Using a naive llama single-domain antibody library and PCR-based maturation, we have produced two closely related nanobodies, H11-D4 and H11-H4, that bind RBD (KD of 39 and 12 nM, respectively) and block its interaction with ACE2. […] Crystal structures of each nanobody-RBD complex revealed how both nanobodies recognize the same epitope, which partly overlaps with the ACE2 binding surface, explaining the blocking of the RBD-ACE2 interaction.
32662203 The known molecular targets of the SARS-CoV-2 include fourteen targets, while four molecules of angiotensin-converting enzyme 2 (ACE2), cathepsin L, 3Cl protease and RNA-dependent RNA polymerase (RdRp) are suggested as more promising potential targets. […] Emphasizing the potential route of SARS-CoV-2 infection and virus entry-related factors like integrins, cathepsin and ACE2 seems valuable.
32662421 The novel coronavirus canonically utilizes the angiotensin-converting enzyme 2 (ACE2) receptor and the serine protease TMPRSS2 for cell entry. […] Herein, building upon our previous single-cell study (Pique-Regi et al., 2019), another study, and new single-cell/nuclei RNA-sequencing data, we investigated the expression of ACE2 and TMPRSS2 throughout pregnancy in the placenta as well as in third-trimester chorioamniotic membranes. […] We report that co-transcription of ACE2 and TMPRSS2 is negligible in the placenta, thus not a likely path of vertical transmission for SARS-CoV-2.
32663051 SARS-CoV-2, like SARS-CoV, uses the Angiotensin-Converting Enzyme 2 (ACE2) cell surface protein for cellular entry. […] An attractive anti-viral approach is targeting virus entry into cells, for which three strategies are suggested: 1) direct targeting of the viral glycoprotein; 2) targeting the viral receptor on the cell surface; and 3) using soluble (s) ACE2 that binds to S protein thereby neutralizing the virus. […] Moreover, we propose that fusion of the sACE2 to anti-CD16 to produce a bi-specific molecule could be a promising anti-viral strategy.
32663362 Angiotensin converting enzyme 2 (ACE2) is the human receptor that interacts with the spike protein of coronaviruses, including the one that produced the 2020 coronavirus pandemic (COVID-19). […] Thus, ACE2 is a potential target for drugs that disrupt the interaction of human cells with SARS-CoV-2 to abolish infection. […] There is also interest in drugs that inhibit or activate ACE2, that is, for cardiovascular disorders or colitis. […] Herein, we review biochemical, chemical biology, and structural information on ACE2, including the recent cryoEM structures of full-length ACE2. […] We conclude that ACE2 is very dynamic and that allosteric drugs could be developed to target ACE2. […] At the time of the 2020 pandemic, we suggest that available ACE2 inhibitors or activators in advanced development should be tested for their ability to allosterically displace the interaction between ACE2 and the spike protein.
32663742 During the COVID-19 infection, the virus blocks ACE2, and angiotensin 1-7 production discontinued.
32664879 In this study, we investigated genetic susceptibility to COVID-19 by examining DNA polymorphisms in ACE2 and TMPRSS2 (two key host factors of SARS-CoV-2) from ~ 81,000 human genomes. […] We found unique genetic susceptibility across different populations in ACE2 and TMPRSS2. […] Specifically, ACE2 polymorphisms were found to be associated with cardiovascular and pulmonary conditions by altering the angiotensinogen-ACE2 interactions, such as p.Arg514Gly in the African/African-American population. […] We further discussed that polymorphisms in ACE2 or TMPRSS2 could guide effective treatments (i.e., hydroxychloroquine and camostat) for COVID-19. […] This study suggested that ACE2 or TMPRSS2 DNA polymorphisms were likely associated with genetic susceptibility of COVID-19, which calls for a human genetics initiative for fighting the COVID-19 pandemic.
32664949 The networks of ACE2 and its interacting molecules were identified using bioinformatic methods. […] We confirmed the binding of SARS-CoV-2 and ACE2 by bioinformatic analysis. […] TMPRSS2, ADAM17, tissue inhibitor of metalloproteinase (TIMP)3, angiotensinogen (AGT), transformation growth factor beta (TGFB1), connective tissue growth factor (CTGF), vascular endothelial growth factor (VEGF) A and fibronectin (FN) were interacted with ACE2, and the mRNA and protein of these molecules were expressed in lung epithelial cells. […] SARS-CoV-2 infection increased ACE2, TGFB1, CTGF and FN1 mRNA that were drivers of lung fibrosis. […] Therefore, SARS-CoV-2 binds with ACE2 and activates fibrosis-related genes and processes to induce lung fibrosis.
32665234 The SARS-CoV-2 virus causing COVID-19 binds human angiotensin-converting enzyme 2 (ACE2) receptors in human tissues. […] ACE2 expression may be associated with COVID-19 infection and mortality rates. […] Routinely prescribed drugs that up- or down-regulate ACE2 expression are, therefore, of critical research interest as agents that might promote or reduce risk of COVID-19 infection in a susceptible population. […] To collate evidence on routinely prescribed drug treatments in the UK that could up- or down-regulate ACE2, and thus potentially affect COVID-19 infection. […] Inclusion criteria will be: (1) assesses the effect of drug exposure on ACE2 level of expression or activity; (2) the drug is included in the British National Formulary (BNF) and, therefore, available to prescribe in the UK; and (3) a control, placebo, or sham group is included as comparator. […] Exclusion criteria will be: (1) ACE2 measurement in utero; (2) ACE2 measurement in children aged <18 years; (3) drug not in the BNF; and (4) review article. […] This systematic review will identify drug therapies that may increase or decrease ACE2 expression.
32665962 The mechanism for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requires the binding of the virus to the angiotensin-converting enzyme 2 (ACE2) receptor, well-known for its role in counteracting ACE. […] ACE2 is involved in modulating blood pressure and establishing blood pressure homeostasis. […] Recently, a critical debatable question has arisen whether using antihypertensive medications will have a favorable impact on people infected with SARS-CoV-2 or a deleterious one, mainly because angiotensin-converting enzyme inhibitor (ACEI) and angiotensin-receptor blocker (ARB) therapy can modulate the expression of ACE2 protein. […] The concern is that the use of ACEIs and ARBs will increase the expression of ACE2 and increase patient susceptibility to viral host cell entry and propagation. […] On the other hand, several genetic association studies have examined the relationship between ACE2 genetic variants and the risk of developing hypertension in different ethnic populations. […] In this review, we discuss the ongoing arguments in the literature about ACE2’s role in mortality rate among coronavirus disease 2019 (COVID-19) patients comorbid with hypertension and critically evaluate the current debate about the usage or discontinuation of ACEI/ARB antihypertensive drugs. […] Moreover, we explore the two opposing roles that ACE2 genetic variants might be playing in COVID-19 by reducing ACE2 receptor effectiveness and mitigating SARS-CoV-2 infectivity.
32668165 First, ACE and ACE2, genes that play key roles in SARS-CoV-2 infection, have some variants that are predicted to reduce the severity of SARS-CoV-2 infection. […] Second, mRNA for ACE2 is elevated and mRNA for TMPRSS2, a serine protease, is decreased in CF airway epithelial cells. […] Increased ACE2 is predicted to enhance SARS-CoV-2 binding to cells but would increase conversion of angiotensin II, which is proinflammatory, to angiotensin-1-7, which is anti-inflammatory. […] Thus, increased ACE2 would reduce inflammation and lung damage due to SARS-CoV-2.
32668443 Here we analyse a large panel of human monoclonal antibodies that target the spike (S) glycoprotein5, and identify several that exhibit potent neutralizing activity and fully block the receptor-binding domain of the S protein (SRBD) from interacting with human angiotensin-converting enzyme 2 (ACE2). […] In addition, passive transfer of either of two of the most potent ACE2-blocking monoclonal antibodies (COV2-2196 or COV2-2381) as monotherapy protected rhesus macaques from SARS-CoV-2 infection.
32668969 Two clusters of actions identified were cytokine storm prevention and angiotensin converting enzyme 2 (ACE2) receptor binding regulation.
32669391 Previously, we have shown that loss of angiotensin-I converting enzyme 2 (ACE2) promotes the ACE/angiotensin-II (Ang-II)/angiotensin type 1 receptor (AT1R) axis, a deleterious arm of RAS, unleashing its detrimental effects in diabetes. […] As suggested by the recent reports regarding the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), upon entry into the host, this virus binds to the extracellular domain of ACE2 in nasal, lung, and gut epithelial cells through its spike glycoprotein subunit S1. […] We put forth the hypothesis that during this process, reduced ACE2 could result in clinical deterioration in COVID-19 patients with diabetes via aggravating Ang-II-dependent pathways and partly driving not only lung but also bone marrow and gastrointestinal pathology.
32669955 Angiotensin-converting enzyme 2 (ACE2) was identified as a functional receptor for SARS-CoV-2, distribution of which may indicate the risk of different human organs vulnerable to SARS-CoV-2 infection. […] Previous studies investigating the distribution of ACE2 mRNA in human tissues only involved a limited size of the samples and a lack of determination for ACE2 protein. […] Indeed, ACE2 is a membrane and secreted protein, while the expression of ACE2 in blood and common blood cells remains unknown. […] Herein, the proteomic data in HIPED and the antibody-based immunochemistry result in HPA were collected to analyze the distribution of ACE2 protein in human tissues. […] The bulk RNA-seq profiles from three separate public datasets including HPA tissue Atlas, GTEx, and FANTOM5 CAGE were also obtained to determine the expression of ACE2 in human tissues. […] Moreover, the abundance of ACE2 in human blood and blood cells was determined by analyzing the data in the PeptideAtlas and the HPA Blood Atlas. […] We found that the mRNA expression cannot reflect the abundance of ACE2 factor due to the strong differences between mRNA and protein quantities of ACE2 within and across tissues. […] Our results suggested that ACE2 protein is mainly expressed in the small intestine, kidney, gallbladder, and testis, while the abundance of which in brain-associated tissues and blood common cells is low. […] HIPED revealed enrichment of ACE2 protein in the placenta and ovary despite a low mRNA level. […] Further, human secretome shows that the average concentration of ACE2 protein in the plasma of males is higher than those in females.
32671936 We review evidence that T2DM with hyperglycemia are among factors that lead to elevated expression of angiotensin-converting enzyme 2 (ACE2) in lungs and other tissues; ACE2 is the cellular “receptor” and port of viral entry.
32672061 In this review, we summarize peptide and peptide-based therapeutics that target one main entry pathway of SARS-CoV-2, which involves the host ACE2 receptor and viral spike (S) protein interaction.
32675206 SARS-CoV, the agent responsible for the 2003 SARS outbreak, utilises angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) host molecules for viral entry. […] ACE2 and TMPRSS2 have recently been implicated in SARS-CoV-2 viral infection. […] To determine the expression and in situ localisation of candidate SARS-CoV-2 receptors in the respiratory mucosa, we analysed gene expression datasets from airway epithelial cells of 515 healthy subjects, gene promoter activity analysis using the FANTOM5 dataset containing 120 distinct sample types, single cell RNA sequencing (scRNAseq) of 10 healthy subjects, proteomic datasets, immunoblots on multiple airway epithelial cell types, and immunohistochemistry on 98 human lung samples.We demonstrate absent to low ACE2 promoter activity in a variety of lung epithelial cell samples and low ACE2 gene expression in both microarray and scRNAseq datasets of epithelial cell populations. […] Consistent with gene expression, rare ACE2 protein expression was observed in the airway epithelium and alveoli of human lung, confirmed with proteomics. […] We present confirmatory evidence for the presence of TMPRSS2, CD147 and GRP78 protein in vitro in airway epithelial cells and confirm broad in situ protein expression of CD147 and GRP78 in the respiratory mucosa.Collectively, our data suggest the presence of a mechanism dynamically regulating ACE2 expression in human lung, perhaps in periods of SARS-CoV-2 infection, and also suggest that alternative receptors for SARS-CoV-2 exist to facilitate initial host cell infection.
32675312 Pandemic COVID-19 by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) infection is facilitated by the ACE2 receptor and protease TMPRSS2. […] Modestly sized case series have described clinical factors associated with COVID-19, while ACE2 and TMPRSS2 expression analyses have been described in some cell types. […] We performed an integrated study of ACE2 and TMPRSS2 gene expression across and within organ systems, by normal versus tumor, across several existing databases (The Cancer Genome Atlas, Census of Immune Single Cell Expression Atlas, The Human Cell Landscape, and more). […] Matched normal tissues generally display higher ACE2 and TMPRSS2 expression compared with cancer, with normal and tumor from digestive organs expressing the highest levels. […] Strong correlations were observed between ACE2 expression levels and multiple immune gene signatures including interferon-stimulated genes and the T cell-inflamed phenotype as well as inverse associations with angiogenesis and transforming growth factor-β signatures. […] ACE2 positively correlated with macrophage subsets across tumor types. […] Single-cell sequencing analysis across nine independent studies demonstrated little to no ACE2 or TMPRSS2 expression in lymphocytes or macrophages. […] ACE2 and TMPRSS2 gene expression associated with commensal microbiota in matched normal tissues particularly from colorectal cancers, with distinct bacterial populations showing strong associations. […] We performed a large-scale integration of ACE2 and TMPRSS2 gene expression across clinical, genetic, and microbiome domains. […] We suggest caution in interpretation regarding genetic associations with ACE2 expression suggested from smaller case series.
32676883 Since the expression of angiotensin-converting enzyme 2 (ACE2) is potentially down-regulated in COVID-19, as proposed by a recent bio-informatic analysis, mechanisms through which reduced ACE2 expressions promote vascular thrombosis are summarized. […] In addition, the reciprocal-enhancing effects of the excessive cytokine release and the downregulated ACE2 expression on their pro-thrombotic activities are further discussed.
32677545 Protein crystal structures of SARS-CoV-2 and ACE2, the compounds hydroxychloroquine and chloroquine, and other ligand structures were minimized by OPLS3 force field. […] Molecular docking studies showed that hydroxychloroquine and chloroquine do not interact with SARS-CoV-2 proteins, but bind to the amino acids ASP350, ASP382, ALA348, PHE40 and PHE390 on the ACE2 allosteric site rather than the ACE2 active site. […] Our results showed that neither hydroxychloroquine and chloroquine bind to the active site of ACE2. […] However, both molecules prevent the binding of SARS-CoV-2 spike protein to ACE2 by interacting with the allosteric site. […] This result can help ACE2 inhibitor drug development studies to prevent viruses entering the cell by attaching spike protein to ACE2.
32678978 Both SARS-CoV-2 spike protein (S-protein), a critical element of the viral entry to the host cell, and ACE2, its docking site on the host cell surface, are extensively glycosylated, making them challenging targets for native MS. […] However, supplementing native MS with a gas-phase ion manipulation technique (limited charge reduction) allows meaningful information to be obtained on the noncovalent complexes formed by ACE2 and the receptor-binding domain (RBD) of the S-protein. […] Using this technique in combination with molecular modeling also allows the role of heparin in destabilizing the ACE2/RBD association to be studied, providing critical information for understanding the molecular mechanism of its interference with the virus docking to the host cell receptor. […] This association alters the protein conformation (to maximize the contiguous patch of the positive charge on the RBD surface), resulting in a notable decrease in its ability to associate with ACE2. […] The destabilizing effect of heparin is more pronounced in the case of the longer chains due to the electrostatic repulsion between the low-pI ACE2 and the heparin segments not accommodated on the RBD surface. […] In addition to providing important mechanistic information on attenuation of the ACE2/RBD association by heparin, the study demonstrates the yet untapped potential of native MS coupled to gas-phase ion chemistry as a means of facilitating rational repurposing of the existing medicines for treating COVID-19.
32679424 This is surprising, considering the recent discovery of the presence of viral receptors (ACE2 and TMPRSS2) in ocular surface tissue.
32679425 As the main receptor of syndrome coronavirus 2 (SARS-CoV-2), angiotensin converting enzyme 2 (ACE2) is also found to be highly expressed not only in respiratory mucosa and alveolar epithelial cells, but also in renal tubule cells, testicular Leydig cells and seminiferous tubule cells. […] In previous studies, it has been found that ACE2 has the ability to regulate autophagy.
32679426 Like SARS-CoV-1, SARS-CoV-2 exploits the ACE2 receptors to enter the host cells; nevertheless, recent bioinformatics insights suggest a potential interaction of SARS-CoV-2 with the «moonlighting protein» CD26/DPP4, exactly how MERS-CoV works.
32680957 Angiotensin-converting enzyme 2 (ACE2) is the canonical cell surface receptor for SARS-CoV-2. […] ACE2 together with angiotensin receptor types 1 and 2 and ACE2 are components of the renin-angiotensin system (RAS). […] Addressing how SARS-CoV-2 unbalances RAS functionality via ACE2 will help design therapies to attenuate a COVID-19-related cytokine storm.
32681121 It has been shown that SARS-CoV-2 utilizes angiotensin converting enzyme 2 (ACE2) as host receptor and host proteases for cell surface binding and internalization. […] Taking advantage of the Network of Italian Genomes (NIG), here we mined whole-exome sequencing data of 6930 Italian control individuals from five different centers looking for ACE2 variants. […] Comparison of ACE2 WES data between a cohort of 131 patients and 258 controls allowed identifying a statistically significant (P value < 0.029) higher allelic variability in controls compared with patients.
32681935 SARS-CoV-2 infection uses the angiotensin-converting enzyme 2 (ACE2) receptor, and typically spreads through the respiratory tract.
32683039 SARS-CoV-2 infects human cells by using angiotensin converting enzyme 2 (ACE2) as a receptor, which is cleaved by transmembrane proteases during host cells infection, thus reducing its activities. […] ACE2 is a relevant player in the renin-angiotensin system (RAS), counterbalancing the deleterious effects of angiotensin II. […] Furthermore, intestinal ACE2 functions as a chaperone for the aminoacid transporter B0AT1. […] It has been suggested that B0AT1/ACE2 complex in the intestinal epithelium regulates gut microbiota (GM) composition and function, with important repercussions on local and systemic immune responses against pathogenic agents, namely virus. […] Notably, productive infection of SARS-CoV-2 in ACE2+ mature human enterocytes and patients’ GM dysbiosis was recently demonstrated. […] This review outlines the evidence linking abnormal ACE2 functions with the poor outcomes (higher disease severity and mortality rate) in COVID-19 patients with pre-existing age-related comorbidities and addresses a possible role for GM dysbiosis.
32683320 Statin-induced upregulation of angiotensin-converting enzyme-2 (ACE2) has the potential to reduce lung injury from excess angiotensin II.
32684166 Further, preliminary data from our research group has demonstrated that WFA does not alter expression of ACE2 in the lungs of tumor-bearing female mice. […] Downregulation of ACE2 has recently been demonstrated to increase the severity of COVID-19. […] Therefore, WFA demonstrates real potential as a therapeutic agent to treat or prevent the spread of COVID-19 due to the reported interference in viral S-protein to host receptor binding and its lack of effect on ACE2 expression in the lungs.
32684351 In this article, we reviewed the current options for COVID-19 therapy including small molecules such as Remdesivir, Favipiravir, Lopinavir/Ritonavir etc, peptide inhibitors of ACE2, Traditional Chinese Medicines and Biologics such as SARS-CoV-2-specific neutralizing antibodies, mesenchymal stem cells and vaccines etc.
32685191 Specifically, the suggestion has been made that ACE inhibitors or ARBs could theoretically contribute to infection via increasing ACE2 receptor expression and hence increase viral load. […] The ACE2 receptor is responsible for binding the SAR-CoV2 viral spike and causing COVID-19 infection. […] What makes the argument somewhat obtuse for ACE inhibitors or ARBs is that ACE2 receptor expression can be increased by compounds that activate or increase the expression of SIRT1. […] Henceforth common dietary interventions, vitamins and nutrients may directly or indirectly influence the cellular expression of the ACE2 receptor. […] There are many common compounds that can increase the expression of the ACE2 receptor including Vitamin C, Metformin, Resveratrol, Vitamin B3 and Vitamin D. […] It is important to acknowledge that down-regulation or blocking the cellular ACE2 receptor will likely be pro-inflammatory and may contribute to end organ pathology and mortality in COVID-19. […] In conclusion from the perspective of the ACE2 receptor, COVID-19 prevention and treatment are distinctly different.
32685221 Membrane-bound angiotensin-converting enzyme 2 (ACE2) has been implicated as the gateway for viral entry into the human cell in causing the infection. […] We also discussed the role of ACE2 and the renin-angiotensin system (RAS) blockade in patients with COVID-19 infection along with pathogenesis.
32686577 Structural analyses have elucidated hot spots in viral binding domains, mutations, and specific proteins in the host such as the receptor angiotensin-converting enzyme 2 (ACE2) and the transmembrane protease serine 2 (TMPRSS2) to be implicated in cell entry and viral infectivity. […] Epigenetic research has revealed that global DNA methylation along with ACE2 gene methylation and post-translational histone modifications may drive differences in host tissue-, biological age- and sex-biased patterns of viral infection.
32687918 Monocytes and macrophages may be infected by SARS-CoV-2 through ACE2-dependent and ACE2-independent pathways.
32689643 The internalization of SARS-CoV-2 is mediated by the binding of the spike glycoprotein of the virus to the angiotensin-converting enzyme 2 (ACE2) on cellular membranes. […] ACE2 is expressed in several tissues including lung alveolar cells, gastrointestinal tissue, and brain. […] SARS-CoV-2 can down-regulate ACE2 and, in turn, overactivate the classical renin-angiotensin system (RAS) axis and decrease the activation of the alternative RAS pathway in the brain.
32690029 No evidence suggests stopping angiotensin-converting-enzyme inhibitors, angiotensin-renin-blockers or statins, even it has been suggested that they may increase the expression of Angiotensin-Converting-Enzyme-2 (ACE2) receptor, which is used by "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to penetrate into the cells.
32690096 We discovered through the autodock simulations that Met124 plays a key role in the efficiency of drugs targeting ACE2, such as remdesivir, chloroquine, ciclesonide and niclosamide, and may be a potential target in COVID-19.
32690544 The coronaviral entry requires the spike (S)-protein for attachment to the host cell surface, and employs human angiotensin-converting enzyme 2 (hACE2) for entry and transmembrane protease serine 2 (TMPRSS2) for S-protein priming. […] Here, we describe the single nucleotide variations (SNVs) in human ACE2 and TMPRSS2. […] The SNVs in SARS-CoV-2/hACE2 contact residues were investigated. […] We detected 349 and 551 SNVs in ACE2 and TMPRSS2, respectively, in a total of 156 513 individuals. […] These SNVs were distributed throughout the coding regions; some ACE2 variants were located in the SARS-CoV-2/hACE2 contact residues, with a hemizygous state occurring in males. […] Using regression analysis, the total numbers of genetic variations in ACE2 and TMPRSS2 were 1.1×103 and 1.5×103, respectively, for a population of one million people. […] The majority of SNVs in ACE2 and TMPRSS2 are rare, population-specific and deleterious, and a multitude of very rare SNVs may explain different susceptibility to SARS-CoV-2.
32691011 We carried out virtual screening of antiviral compounds targeting the spike glycoprotein (S), main protease (Mpro), and the SARS-CoV-2 receptor binding domain (RBD)-angiotensin-converting enzyme 2 (ACE2) complex of SARS-CoV-2. […] Furthermore, the postfusion conformation of the trimeric S protein RBD with ACE2 revealed conformational changes associated with PC786 drug binding.
32691370 Angiotensin-converting enzyme 2 (ACE2) plays an important role as a member of the renin-angiotensin-aldosterone system (RAAS) in regulating the conversion of angiotensin II (Ang II) into angiotensin (1-7) (Ang [1-7]). […] But at the same time, while expressed on the surface of human cells, ACE2 is the entry receptor for SARS-CoV-2. […] We demonstrate for the first time that ACE2 and the entry-facilitating transmembrane protease TMPRSS2 are expressed on very small CD133+CD34+Lin-CD45- cells in human umbilical cord blood (UCB), which can be specified into functional HSCs and EPCs. […] Moreover, we demonstrate for the first time that, in human VSELs and HSCs, the interaction of the ACE2 receptor with the SARS-CoV-2 spike protein activates the Nlrp3 inflammasome, which if hyperactivated may lead to cell death by pyroptosis. […] We also report that ACE2 is expressed on the surface of murine bone marrow-derived VSELs and HSCs, although it is known that murine cells are not infected by SARS-CoV-2. […] Graphical Abstract •Human VSELs and HSCs express ACE2 receptor for SARS-CoV2 entry. […] •Interaction of viral spike protein with ACE2 receptor may hyperactivate Nlrp3 inflammasome which induces cell death by pyroptosis.
32691697 Here we discuss few natural secondary metabolites (Delphinidin 3,5-diglucoside, Scutellarein 7-glucoside, Avicularin and 3,5-Di-O-galloylshikimic acid) that showed encouraging binding affinity against coronavirus main protease (Mpro) and human ACE2 receptor with MM-GBSA energies up to -74.0 Kcal/mol and -79.5 Kcal/mol, respectively.
32691890 It has been suggested that some individuals may present genetic susceptibility to SARS-CoV-2 infection, with particular research interest in variants of the ACE2 and TMPRSS2 genes, involved in viral penetration into cells, in different populations and geographic regions, although insufficient information is currently available. […] Through whole-exome sequencing, the frequency of exonic variants of the ACE2, TMPRSS2, and Furin genes was analyzed in relation to presence or absence of SARS-CoV-2 infection in a familial multiple sclerosis cohort including 120 individuals from Madrid. […] The ACE2 gene showed a low level of polymorphism, and none variant was significantly associated with SARS-CoV-2 infection.
32693122 Its closest relative, SARS-CoV-1, has a slightly mutated Spike (S) protein, which interacts with ACE2 receptor in human cells to start the infection. […] By binding to the S protein, both peptides led to conformational alterations in the protein, resulting in incorrect interaction with ACE2. […] Therefore, given the importance of the S protein-ACE2 interaction for SARS-CoV-2 infection, synthetic peptides could block SARS-CoV-2 infection.
32695320 Studies show that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), similar to its predecessor SARS-CoV, engages angiotensin-converting enzyme 2 (ACE2) as the entry receptor. […] ACE2 is also expressed in the heart, providing a link between coronaviruses and the cardiovascular system.
32695327 Recent data have shown that severe acute respiratory syndrome coronavirus 2 can infect renal proximal tubular cells via Angiotensin Converting Enzyme 2 (ACE2) .
32696234 We scanned the literature for evidence on drugs that target the virus entry machinery into host cells and consist mainly of ACE2 and TMPRSS2, as well as other cellular molecules regulating ACE2 expression, such as ADAM-17 and calmodulin. […] They include recombinant soluble ACE2, indirect ACE2 modulators (angiotensin receptor blockers, calmodulin antagonists, selective oestrogen receptor modifiers), TMPRSS2 inhibitors (camostat mesylate, nafamostat mesylate, antiandrogens, inhaled corticosteroids) and ADAM-17 enhancers (5-fluorouracil).
32696312 Extensive reports from China documented central and peripheral nervous system involvement in patients with COVID-19, and identified in angiotensin converting enzyme2 (ACE2), which is present in multiple human organs, the functional receptor for this virus.
32698249 Several X-linked genes (such as ACE2) and Y-linked genes (SRY, SOX9) may explain sex differences.
32698689 Spike glycoprotein engages host Angiotensin-converting enzyme 2 (ACE2) receptors for entry into host cells, where the receptor recognition and attachment of spike glycoprotein to the ACE2 receptors is a prerequisite step and key determinant of the host cell and tissue tropism. […] Binding of spike glycoprotein to the ACE2 receptor triggers a cascade of structural transitions, including transition from a metastable pre-fusion to a post-fusion form, thereby allowing membrane fusion and internalization of the virus. […] Further, our molecular dynamics (MD) simulation and energy landscape studies with fisetin, quercetin, and kamferol revealed that these molecules bind with the hACE2-S complex with low binding free energy. […] The study provided an indication that these molecules might have the potential to perturb the binding of hACE2-S complex.
32699095 Despite these variations, some bat SARSr-CoVs can utilize the orthologs of the human SARS-CoV receptor, angiotensin-converting enzyme 2 (ACE2), for entry. […] It is speculated that the interaction between bat ACE2 and SARSr-CoV spike proteins drives diversity. […] Here, we identified a series of R. sinicus ACE2 variants with some polymorphic sites involved in the interaction with the SARS-CoV spike protein. […] Pseudoviruses or SARSr-CoVs carrying different spike proteins showed different infection efficiencies in cells transiently expressing bat ACE2 variants. […] All tested bat SARSr-CoV spike proteins had a higher binding affinity to human ACE2 than to bat ACE2, although they showed a 10-fold lower binding affinity to human ACE2 compared with that of their SARS-CoV counterpart. […] Structure modeling revealed that the difference in binding affinity between spike and ACE2 might be caused by the alteration of some key residues in the interface of these two molecules. […] These results suggest that the SARSr-CoV spike protein and R. sinicus ACE2 may have coevolved over time and experienced selection pressure from each other, triggering the evolutionary arms race dynamics.IMPORTANCE Evolutionary arms race dynamics shape the diversity of viruses and their receptors. […] Here, we show the highly polymorphic ACE2 in Chinese horseshoe bat populations. […] These ACE2 variants support SARS-CoV and SARSr-CoV infection but with different binding affinities to different spike proteins. […] The higher binding affinity of SARSr-CoV spike to human ACE2 suggests that these viruses have the capacity for spillover to humans. […] The positive selection of residues at the interface between ACE2 and SARSr-CoV spike protein suggests long-term and ongoing coevolutionary dynamics between them.
32700580 The COVID-19 pandemic is caused by the severe acute-respiratory-syndrome-coronavirus-2 that uses ACE2 as its receptor. […] Drugs that raise serum/tissue ACE2 levels include ACE inhibitors (ACEIs) and angiotensin-II receptor blockers (ARBs) that are commonly used in patients with hypertension, cardiovascular disease and/or diabetes. […] Increasing ACE2 could potentially increase the risk of infection, severity or mortality in COVID-19 or it might be protective as it forms angiotensin-(1-7) which exhibits anti-inflammatory/anti-oxidative effects and prevents diabetes- and/or hypertension-induced end-organ damage. […] Here, we review studies implicating 15 classes of drugs in increasing ACE2 levels in vivo and the available literature on the clinical safety of these drugs in COVID-19 patients. […] For definitive clarity, further clinical and mechanistic studies are needed in assessing the safety of all classes of ACE2 raising medications.
32700671 While genetically distinct, SARS-CoV-1, the aetiological agent responsible for an outbreak of severe acute respiratory syndrome (SARS) in 2002-2003, utilises the same host cell receptor as SARS-CoV-2 for entry: angiotensin-converting enzyme 2 (ACE2). […] Parts of the SARS-CoV-1 spike glycoprotein (S protein), which interacts with ACE2, appear conserved in SARS-CoV-2.
32700795 The infectious process initiates via binding of SARS-CoV-2 Spike (S) glycoprotein to host angiotensin-converting enzyme 2 (ACE2). […] The interaction is mediated by the receptor-binding domain (RBD) of S glycoprotein, promoting host receptor recognition and binding to ACE2 peptidase domain (PD), thus representing a promising target for therapeutic intervention. […] Although targeting PPI remains a challenge in drug discovery, our investigation highlights that interaction between SARS-CoV-2 RBD and ACE2 PD might be prone to small molecule modulation, due to the hydrophilic nature of the bi-molecular recognition process and the presence of druggable hot spots.
32704169 Our simple and rapid test is based on antibody-mediated blockage of the interaction between the angiotensin-converting enzyme 2 (ACE2) receptor protein and the receptor-binding domain.
32705298 Then angiotensin-converting enzyme 2 (ACE2) as the binding site of SARS-CoV‑2 and the possible influence on the disease susceptibility are explained.
32707096 However, a recent report of ACE2, the host factor mediating SARS-Cov-2 infection, identifying it as interferon-stimulated raised considerable safety concern.
32707445 We confirmed that SARS-CoV-2 infects cells via angiotensin converting enzyme 2 (ACE2), the functional receptor for SARS-CoV, and we also found that the recombinant receptor binding domain (RBD) of the S protein of SARS-CoV effectively inhibits ppSARS-2 entry in Huh7.5 cells. […] Our study demonstrates that although both SARS-CoV and SARS-CoV-2 use ACE2 as a cellular receptor, the neutralization epitopes are not shared by these two closely-related viruses, highlighting challenges towards developing a universal vaccine against SARS-CoV related viruses.
32707942 Analyses of the clinical trials were grouped as chemotherapy, serotherapy, anticoagulant, and the use of human recombinant soluble ACE2 therapies.
32708112 The Angiotensin Converting Enzyme 2 (ACE2) is the SARS-CoV2 functional receptor.
32708205 The new coronavirus SARS-CoV-2, responsible for the Covid-19 pandemic, uses the angiotensin converting enzyme type 2 (ACE2), a physiological inhibitor of the renin angiotensin aldosterone system (RAAS), as a cellular receptor to infect cells.
32708755 Based purely on experimental studies in which RAS pathway inhibitors were administered in vivo to humans/rodents, a reasonable hypothesis of using inhibitors that block both ACE and ACE2 zinc metalloproteases and their downstream pathways in COVID-19 patients will be proposed.
32709462 While aspects of pregnancy, including higher expression of the cell receptor for the virus, ACE2, could put these women at higher risk, preliminary epidemiological information does not support this.
32710575 Its aetiological agent, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), requires angiotensin converting enzyme 2 (ACE2) for cellular entry. […] The commonly used angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) could affect SARS-CoV-2 infectivity and may alter COVID-19 disease progression by altering ACE2 expression. […] Current evidence of ACEI/ARB-ACE2 interaction as well as the effects of ACEIs/ARBs on viral-associated acute lung injury is summarized and discussed in this review.
32711111 It does so by binding to host cell angiotensin converting enzyme 2 (ACE2) receptors, leading to endocytosis with the receptor, and subsequently using the host cell’s machinery to replicate copies of itself and invade new cells. […] The extent of the spread of infection in the body is dependent on the pattern of ACE2 expression and overreaction of the immune system. […] Additionally, by inducing an imbalance in the renin-angiotensin-aldosterone system (RAAS) and the loss of ACE2 would favour the progression of inflammatory and thrombotic processes in the lungs.
32712124 The link of these morbidities with renin angiotensin system (RAS) and angiotensin converting enzyme-2 (ACE2) as the site of the multiplication of COVID-19 has widely been accepted.
32712300 SARS-CoV-2 infects human cells via the binding of its S protein to the receptor angiotensin-converting enzyme (ACE2). […] The use of ACEIs/ARBs (RAAS inhibitors) regulates the renin-angiotensin-aldosterone system (RAAS) and may increase ACE2 expression. […] In this review, we summarize preclinical and clinical studies to investigate whether the use of ACEIs/ARBs increases ACE2 expression in animals or patients.
32713161 Despite angiotensin-converting enzyme 2 (ACE2), the recently recognized receptor of SARS-CoV and SARS-CoV-2, which facilitated their entries into the host, DPP-4 has been identified as the receptor of middle east respiratory syndrome coronavirus (MERS-CoV).
32714335 Chloroquine appears to inhibit in vitro SARS virus’ replication and to interfere with SARS-CoV2 receptor (ACE2).
32714336 Systemic decrease in ACE2 function impacts the Renin-Angiotensin-Kallikrein-Kinin systems (RAS-KKS) increasing clotting.
32714688 COVID-19 virus may be present in stool samples of patients infected with COVID-19, and angiotensin-converting enzyme 2 (ACE2) is a receptor for this virus, which is substantially present in GI epithelial cells.
32715080 SARS-CoV-2 infects host cells through ACE2 receptors, leading to COVID-19-related pneumonia.
32715618 The key protein suggested to be involved in host cell entry is angiotensin I converting enzyme 2 (ACE2). […] Here, we report the expression pattern of ACE2 across > 150 different cell types corresponding to all major human tissues and organs based on stringent immunohistochemical analysis. […] ACE2 expression was mainly observed in enterocytes, renal tubules, gallbladder, cardiomyocytes, male reproductive cells, placental trophoblasts, ductal cells, eye, and vasculature.
32715628 The angiotensin converting enzyme 2 (ACE2) has been suggested to be the key protein used by SARS-CoV-2 for host cell entry. […] In their recent work, Lindskog and colleagues (Hikmet et al, 2020) report that ACE2 is expressed at very low protein levels-if at all-in respiratory epithelial cells.
32716553 Lung tissue sections from patients suffering from lung cancer were used for immunohistochemistry study of angiotensin-converting enzyme II (ACE2) expression. […] COPD patients had increased, whereas asthmatics had decreased ACE2 protein expression in lower airways, compared with that in control subjects without asthma and COPD. […] IL-4 and IL-13 downregulated, but TNF-α, IL-12, and IL-17A upregulated ACE2 expression in BEAS-2B cells. […] Patients with asthma and COPD likely have different risk of severe COVID-19, which may be associated with different ACE2 expression.
32716648 The 2019-nCoV patients showed that the angiotensin-converting enzyme II (ACE2) was the same for SARS-CoV.
32717345 The reports indicate the ability of SARS-CoV-2 to affect almost any organ due to the presence of a receptor known as angiotensin converting enzyme 2 (ACE2) across the body. […] ACE2 receptor is majorly expressed in the brush border of gut enterocytes along with the ciliated cells and alveolar epithelial type II cells in the lungs. […] The amino acid transport function of ACE2 has been linked to gut microbial ecology in gastrointestinal (GI) tract, thereby suggesting that COVID-19 may, to some level, be linked to the enteric microbiota.
32718670 Of interest, another mechanistic approach responds to considering the inhibition of the renin-angiotensin-aldosterone system (RAAS), which is exacerbated in COVID-19 infection because the virus binds to the enzyme ACE2, making more angiotensinII available to cause damage. […] VitaminD inhibits mediators of RAAS - present in all cells of the body - and by inhibiting ACE activity and increasing ACE2, it lowers angiotensinII levels.
32719447 Moreover, SARS-CoV-2 tropism and interaction with the RAAS system, through ACE2 receptor, possibly enhances inflammation response and cardiac aggression, leading to imperative concerns about the use of ACEi and ARBs in infected patients.
32719619 Firstly, SARS-CoV-2 exhibits marked tropism for cells that harbor the membrane-bound metalloprotease angiotensin-converting enzyme 2 (ACE2) at their plasmalemma, predominantly in cells lining the oral cavity, upper respiratory tract, and bronchoalveolar cells, making these epithelial mucosae the most likely viral receptor cell targets and entry routes. […] Thirdly, viral entry of other viruses has been successfully blocked by inhibiting viral endogenous proteases or clathrin/dynamin-dependent endocytosis, the same internalization pathway followed by ACE2 and some viruses.
32719799 Targeting the structural proteins or cellular receptors of 2019-nCoV, including coronavirus chymotrypsin-like (3CLpro or Mpro), helicase (nsP13), S protein, and human angiotensin converting enzyme 2 (ACE2), holds promise for preventing infection.
32719819 According to big data analysis, there are many proteins homologous to or interacting with the angiotensin-converting enzyme 2 (ACE2), which, therefore, may not be the only receptor for the novel coronavirus; other receptors may also exist in host cells of different species. […] We analyzed the proteins coded by the ACE2 gene in different mammalian species and predicted their correlation and homology with the human ACE2 receptor. […] The major finding of our predictive analysis suggested ACE2 gene-encoded proteins to be highly homologous across mammals.
32720031 A number of studies have demonstrated that 2019-nCoV and the SARS-CoV shared the same cell entry receptor named angiotensin-converting enzyme 2 (ACE2).
32720082 Abnormal cardiac biomarkers are common in COVID-19 and can stem from a variety of mechanisms that involve the viral entry itself through the ACE2 receptors, direct cardiac injury, increased thrombotic activity, stress cardiomyopathy, and among others.
32720223 This systemic involvement is postulated to be mainly related to the SARS-CoV-2 virus binding on angiotensin-converting enzyme 2 (ACE2) receptors located on several different human cells.
32721806 Angiotensin-converting enzyme-2 (ACE2) receptor, regulation of the renin-angiotensin-aldosterone system (RAAS), and transmembrane serine protease 2 (TMPRSS2) action are critical for the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) cell entry and infectivity. […] ACE2 expression and RAAS are abnormal in hypertension and obesity, while TMPRSS2 is overexpressed when exposed to androgens, which may justify why these factors are overrepresented in COVID-19. […] Current data shows that spironolactone may concurrently mitigate abnormal ACE2 expression, correct the balances membrane-attached and free circulating ACE2 and between angiotensin II and Angiotensin-(1-7) (Ang-(1-7)), suppress androgen-mediated TMPRSS2 activity, and inhibit obesity-related RAAS dysfunctions, with consequent decrease of viral priming.
32721809 ACE2 has anti-inflammatory, anti-fibrotic and anti-proliferative characteristics through converting angiotensin (Ag)-II to Ang (1-7). […] ACE2 receptor is downregulated by the SARS-COV through the spike protein of SARS-CoV (SARS-S) via a process that is tightly coupled with Tumor necrosis factor (TNF)-α production. […] Affected children by COVID-19 with genetically-susceptible to KD might have genetically under-expression of ACE2 receptor that might further decrease the expression of ACE2 due to the downregulation of the receptor by the virus in these patients. […] It appears that TNF- α might be the cause and the consequence of the ACE2 receptor downregulation which results in arterial walls aneurysm. […] Conclusion: Genetically under-expression of ACE2 receptor in children with genetically-susceptible to KD who are infected with SARS-CoV-2 possibly further downregulates the ACE2 expression by TNF-α and leads to surge of inflammation including TNF-α and progression to Kawasaki-like disease.
32721814 In trying to understand the biochemical mechanism involved in the recent pandemic COVID-19, there is currently growing interest in angiotensin-converting enzyme II (ACE2).
32722164 Nrf2 reduces angiotensin-converting enzyme 2 (ACE2) receptors expression in respiratory epithelial cells. […] SARS-CoV2 has a high affinity for ACE2 that works as receptors for coronavirus surface spike glycoprotein, facilitating viral entry. […] Therefore, this hypothesis paper describes the use of flavonoid supplements combined with vitamin D3 to activate Nrf2, which may be a potential target to prevent and/or decrease SARS-CoV-2 infection severity, reducing oxidative stress and inflammation, enhancing innate immunity, and downregulating ACE2 receptors.
32723427 Because human angiotensin-converting enzyme 2 (ACE2) is the receptor for SARS-CoV-2, mice expressing the human ACE2 gene have shown promise as a potential model for COVID-19. […] Five mice from the transgenic mouse strain K18-hACE2 were intranasally inoculated with SARS-CoV-2 Hong Kong/VM20001061/2020. […] Overall, these results show that the K18-hACE2 transgenic background can be used to establish symptomatic SARS-CoV-2 infection and can be a useful mouse model for COVID-19.
32723443 The presence in kidney of angiotensin-converting enzyme 2 (ACE2), a receptor for the virus, has been proven, but few cases of direct viral presence in kidney tissue have been published.
32724171 SARS-CoV-2 itself is not a recombinant of any sarbecoviruses detected to date, and its receptor-binding motif, important for specificity to human ACE2 receptors, appears to be an ancestral trait shared with bat viruses and not one acquired recently via recombination.
32725927 Angiotensin converting enzyme 2 (ACE2) plays an important role in inflammation, which is attributable at least, in part, to the conversion of the pro-inflammatory angiotensin (Ang) II peptide into angiotensin 1-7 (Ang 1-7), a peptide which opposes the actions of AngII. […] ACE2 and AngII are present in many tissues but information on the cornea is lacking. […] We observed that mice deficient in the Ace2 gene (Ace2-/-), developed a cloudy cornea phenotype as they aged. […] Corneal epithelial debridement experiments in young ACE2-deficient mice showed normal appearing corneas, devoid of haze. […] Since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes human ACE2 as the receptor for entry with subsequent downregulation of ACE2, corneal inflammation in Ace2-/- mice may have a similar mechanism with that in COVID-19 patients. […] Thus the Ace2-/- cornea, because of easy accessibility, may provide an attractive model to explore the molecular mechanisms, immunological changes, and treatment modalities in patients with COVID-19.
32726128 Testosterone on the contrary enhances the levels of the two most critical molecules, angiotensin-converting enzyme 2 (ACE2) and the transmembrane protease serine-type 2 (TMPRSS2), transcriptionally and posttranslationally, thereby increasing viral load and delaying viral clearance in men as compared with women.
32726325 Development of novel approaches for regulating the expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) is becoming increasingly important within the context of the ongoing COVID-19 pandemic since these enzymes play a crucial role in cell infection. […] In this work we searched for putative ACE2 and TMPRSS2 expression regulation networks mediated by various miRNA isoforms (isomiR) across different human organs using publicly available paired miRNA/mRNA-sequencing data from The Cancer Genome Atlas (TCGA) project. […] As a result, we identified several miRNA families targeting ACE2 and TMPRSS2 genes in multiple tissues. […] In particular, we found that lysine-specific demethylase 5B (JARID1B), encoded by the KDM5B gene, can indirectly affect ACE2 / TMPRSS2 expression by repressing transcription of hsa-let-7e / hsa-mir-125a and hsa-mir-141 / hsa-miR-200 miRNA families which are targeting these genes.
32726802 As an essential step during infection, SARS-CoV-2 uses the receptor-binding domain (RBD) of the spike protein to engage with the receptor angiotensin-converting enzyme 2 (ACE2) on host cells1,2. […] The sera from the immunized animals blocked the binding of the RBD to ACE2, which is expressed on the cell surface, and neutralized infection with a SARS-CoV-2 pseudovirus and live SARS-CoV-2 in vitro.
32727845 Docking studies revealed that the scFv recognizes an epitope that partially overlaps with angiotensin-converting enzyme 2 (ACE2)-interacting sites on the CoV-2 RBD.
32728654 SARS-CoV-2 attaches to the ACE2 system in the pancreas causing perturbation of insulin production resulting in hyperglycemic emergencies.
32729064 SARS-CoV-2 enters into the cell via receptors present on the cell surface named angiotensin-converting enzyme 2 (ACE2) receptor. […] Notwithstanding ACE2 receptors acts as a gateway for infection, and most of the cardiovascular patients are treated with the ACE inhibitors. […] Also, the effect of ACE inhibitors varies with the polymorphism in ACE2 receptors present in the individuals.
32729248 Angiotensin-converting enzyme 2 (ACE2) is the host receptor for SARS-CoV-2 entry. […] Recent studies have suggested that patients with hypertension and diabetes treated with ACE inhibitors (ACEIs) or angiotensin receptor blockers have a higher risk of COVID-19 infection as these drugs could upregulate ACE2, motivating the study of ACE2 modulation by drugs in current clinical use. […] Here, we mined published datasets to determine the effects of hundreds of clinically approved drugs on ACE2 expression. […] We find that ACEIs are enriched for ACE2-upregulating drugs, while antineoplastic agents are enriched for ACE2-downregulating drugs. […] Vorinostat and isotretinoin are the top ACE2 up/downregulators, respectively, in cell lines. […] Dexamethasone, a corticosteroid used in treating severe acute respiratory syndrome and COVID-19, significantly upregulates ACE2 both in vitro and in vivo. […] Further top ACE2 regulators in vivo or in primary cells include erlotinib and bleomycin in the lung and vancomycin, cisplatin, and probenecid in the kidney. […] Our study provides leads for future work studying ACE2 expression modulators.
32729433 The potential ocular presence of the SARS-CoV-2 in the eye of a patient can target ACE2 receptors in the endothelium of the conjunctival vessels and use the lacrimal sac a potential space to evade immune detection and clinical isolation.
32729463 Emerging reports of encephalopathies and similar ailments with the detection of the virus in the CSF has elicited an urgent need for investigating the possibility of neuroinvasiveness of the virus, which cannot be ruled out given the expression of low levels of ACE2 receptors in the brain.
32729633 COVID-19 is caused by SARS-CoV-2, a betacoronavirus that uses the angiotensin-converting enzyme-related carboxypeptidase (ACE2) receptor to gain entry into cells. […] ACE2 receptor is widely expressed in multiple organs, including the retina, an extension of the central nervous system. […] The ACE2 receptor is involved in the diabetic and hypertensive retinopathy.
32730512 This classical pathway is also regulated by ACE2, which converts AngI to Ang 1-9, and degrades AngII to Ang 1-7, whose vasodilatory and anti-inflammatory functions balance out the effects of AngII. […] ACE2 has been associated with the pathogenesis of respiratory infections such as RSV and severe acute respiratory syndrome coronavirus (SARS-CoV and SARS-CoV-2). […] Recent studies have shown that ACE2 corresponds to the main SARS-CoV-2 receptor, which together with other receptors such as the TMPRSS2, allows the virus to attach, fuse, and enter the host cell. […] These studies have shown that in animals infected with coronavirus there is a drop in tissue concentration of ACE2 and Ang 1-7, leading to overexpression of AngII and its vasoconstrictive and inflammatory effects. […] Experiments with recombinant ACE2 have shown a protective effect against overexpression of RAAS in coronavirus-infected animals, which is similar to that demonstrated with the use of AngII receptor blockers (AT1). […] Evidence on the protective role of ACE2 seems to support the recommendations re garding not discontinuing these drugs in COVID-19 infection.
32730589 This protein is fundamental for binding in human ACE2 and further use as an entry receptor to invade target cells.
32733785 Human angiotensin-converting enzyme 2 (hACE2) has recently received a great attention due to it play a critical role as SARS-CoV receptor in the infection of human body. […] However, no further analysis for gene regulation has been performed in target tissues of model mice during hACE2 overproduction. […] To characterize changes in global gene expression in the hearts and kidneys of rtTA/hACE2 double transgenic (dTg) mice in response to hACE2 overexpression, total RNA extracted from these tissues from dTg mice after doxycycline (Dox) treatment was hybridized to oligonucleotide microarrays. […] Briefly, dTg mice were generated by cross-mating pα-MHC/rtTA Tg mice with pTRE/hACE2 Tg mice. […] The expression level of hACE2 protein was determined to be high in hearts, kidneys, and brains of dTg mice, whereas lung, liver, and testis tissues expressed low levels. […] The level of hACE2 was significantly enhanced in hearts and kidneys of the Dox+dTg group compared to that in Vehicle+dTg mice although consistent levels of mouse ACE2 (mACE2) remained in the same tissues. […] Taken together, these findings suggested that several functional groups and individual genes can be considered biomarkers that respond to hACE2 overexpression in dTg mice.
32734518 As a result, the COVID-19 lifecycle were categorized as following steps: “Host Cell Attachment” which is mainly conducted with ACE2 receptors and TMPRSS2 from the host cell and Spike (S) protein, “Endocytosis Pathway” which is performed mainly by clathrin-mediated endocytosis, and “Viral Replication” which contains translation and replication of RNA viral genome.
32735849 An anticipated correlate of such countermeasures is the level of neutralizing antibodies against the SARS-CoV-2 spike protein, which engages with host ACE2 receptor for entry. […] Comparing the neutralizing activities of various antibodies and ACE2-Fc soluble decoy protein in both assays revealed a high degree of concordance.
32735889 Angiotensin II, converted by angiotensin-converting enzyme (ACE) from angiotensin I and metabolized by ACE 2 (ACE2), plays a pivotal role in the pathogenesis of lung injury. […] ACE2 is identified as an essential receptor for SARS-CoV-2 to enter the cell. […] The binding of ACE2 and SARS-CoV-2 leads to the exhaustion and down-regulation of ACE2. […] The interaction and imbalance between ACE and ACE2 result in an unopposed angiotensin II.
32735992 The interaction between the angiotensin-converting enzyme 2 (ACE2) and the receptor binding domain (RBD) of the spike protein from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays a pivotal role in virus entry into the host cells. […] Since recombinant ACE2 protein has been suggested as an anti-SARS-CoV-2 therapeutic agent, this study was conducted to design an ACE2 protein with more desirable properties. […] In this regard, the amino acids with central roles in enzymatic activity of the ACE2 were substituted. […] Moreover, saturation mutagenesis at the interaction interface between the ACE2 and RBD was performed to increase their interaction affinity. […] The best mutations to increase the structural and thermal stability of the ACE2 were also selected based on B factors and mutation effects. […] The obtained resulted revealed that the Arg273Gln and Thr445Gly mutation have drastically reduced the binding affinity of the angiotensin-II into the active site of ACE2. […] The Pro451Met mutation along with the Gly448Trp mutation was predicted to increase the thermodynamic stability and thermostability of the ACE2. […] The designed therapeutic ACE2 would have no enzymatic activity while it could bear stronger interaction with Spike glycoprotein of the SARS-CoV-2. […] This engineered ACE2 could be exploited as a novel therapeutic agent against COVID-19 after necessary evaluations.
32736307 Severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 lights the wick by infecting alveolar epithelial cells (AECs) and downregulating the angiotensin converting enzyme-2 (ACE2)/angiotensin (Ang-1-7)/Mas1R axis. […] Downregulation of the ACE2/Ang-(1-7)/Mas1R axis leaves the lung without a critical defense mechanism and turns the scale to the inflammatory side of the RAS.
32736832 ACE2 protein found on the cell membranes is the target of SARS-CoV-2 for entering into the host cells. […] Viral spike protein-binding with ACE2 down-regulates it. […] As ACE2 is known to protect the lung from injuries, SARS-CoV-2-induced ACE2 deficiency may expose patients to lung damage. […] AT1R antagonists and vitamin D increase the expression of ACE2 independently.
32737423 We also summarize the current knowledge regarding the pathophysiology of SARS-CoV-2 infection with an emphasis on ACE2, the cardiovascular system, and the kidney.
32737466 EY6A Fab binds the receptor binding domain (RBD) of the viral spike glycoprotein tightly (KD of 2 nM), and a 2.6-Å-resolution crystal structure of an RBD-EY6A Fab complex identifies the highly conserved epitope, away from the ACE2 receptor binding site.
32738184 While the virus uses angiotensin-converting enzyme 2 (ACE2) as the primary entry receptor, the recent experimental and clinical findings suggest that some tumor markers, including CD147 (basigin), can provide an additional entry for SARS-CoV-2 infection through binding to the viral spike (S) protein.
32738306 The receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein binds to the cell surface angiotensin-converting enzyme 2 (ACE2) receptor, allowing virus entry and replication in host cells. […] The findings showed AZM affinity scores (ΔG) with strong interactions with ACE2, CTSL, Mpro and RBD. […] CQ affinity scores showed three low-energy results (less negative) with ACE2, CTSL and RBD, and a firm bond score with Mpro. […] For HCQ, two results (ACE2 and Mpro) were firmly bound to the receptors, however CTSL and RBD showed low interaction energies. […] The differences in better interactions and affinity between HCQ and CQ with ACE2 and Mpro were probably due to structural differences between the drugs.
32738617 SARS-CoV-2, as other coronaviruses, binds its target cells through the angiotensin-converting enzyme 2 (ACE2) receptor. […] Accordingly, this makes ACE2 research essential for understanding the zoonotic nature of coronaviruses and identifying novel drugs. […] Here we present a systematic analysis of the ACE2 conservation and co-evolution protein network across 1,671 eukaryotes, revealing an unexpected conservation pattern in specific metazoans, plants, fungi, and protists. […] These drugs are expected to perturb the ACE2 network affecting infectivity as well as the pathophysiology of the disease.
32738628 Considering the published literature on medicinal importance, 154 phytochemicals with analogous structure from limonoids and triterpenoids were selected to search potential inhibitors for the five therapeutic protein targets of SARS-CoV-2, i.e., 3CLpro (main protease), PLpro (papain-like protease), SGp-RBD (spike glycoprotein-receptor binding domain), RdRp (RNA dependent RNA polymerase) and ACE2 (angiotensin-converting enzyme 2).
32739642 Angiotensin-converting enzyme 2 (ACE2) is a membrane-bound zinc metallopeptidase that generates the vasodilatory peptide angiotensin 1-7 and thus performs a protective role in heart disease. […] It is considered an important therapeutic target in controlling the COVID-19 outbreak, since SARS-CoV-2 enters permissive cells via an ACE2-mediated mechanism. […] The present in silico study attempted to repurpose existing drugs for use as prospective viral-entry inhibitors targeting human ACE2. […] The results of the calculations suggest that lividomycin, burixafor, quisinostat, fluprofylline, pemetrexed, spirofylline, edotecarin, and diniprofylline emerge as promising repositionable drug candidates for stabilizing the closed (substrate/inhibitor-bound) conformation of ACE2, thereby shifting the relative positions of the receptor’s critical exterior residues recognized by SARS-CoV-2. […] This study is among the rare ones in the relevant scientific literature to search for potential ACE2 inhibitors. […] In practical terms, the drugs, unmodified as they are, may be introduced into the therapeutic armamentarium of the ongoing fight against COVID-19 now, or their scaffolds may serve as rich skeletons for designing novel ACE2 inhibitors in the near future.
32739645 Despite anticipated increased risk of COVID-19 and increased expression of the SARS CoV-2 receptor (ACE2), the relatively low mortality of pregnant women with COVID-19 has been an area of wonder.
32740495 : ACE2 receptor has a broad expression pattern in the cellular membrane and provides a protective action against the development of cardiovascular diseases. […] This virus invades alveolar epithelium and cardiomyocytes using ACE2 as a transmembrane receptor. […] ACE2 is a counter-regulatory peptide that degrades Ang II into Ang 1-7, thereby attenuating the biological effects of the AT1 receptor. […] The binding between the spike protein of COVID-19 and the enzyme is crucial for the virus to enter the target cells, but whether an increase in ACE2 activity could facilitate the infection is not yet demonstrated. […] It appears that cellular infection leads to a reduction in ACE2 expression and an increase in the activity of the Ang II–AT1 axis, which leads to the release of pro-inflammatory cytokines, ARDS, myocarditis, and hypercoagulability with the possibility of exacerbation of acute coronary syndrome, induction of pulmonary embolism, or appearance of disseminated intravascular coagulation.
32740825 To select potential molecules that can target viral spike proteins, which may potentially interrupt the interaction between the human angiotension-converting enzyme 2 (ACE2) receptor and viral spike protein by virtual screening. […] The three-dimensional (3D)-coordinate file of the receptor-binding domain (RBD)-ACE2 complex for searching a suitable docking pocket was firstly downloaded and prepared.
32741970 None have shown placental expression of the ACE2 or TMPRSS2 protein, both required for viral infection. […] We examined 19 COVID-19 exposed placentas for histopathologic findings, and for expression of ACE2, and TMPRSS2 by immunohistochemistry. […] ACE2 membranous expression in the syncytiotrophoblast (ST) of the chorionic villi is predominantly in a polarized pattern with expression highest on the stromal side of the ST. […] In addition, cytotrophoblast and extravillous trophoblast express ACE2. […] No ACE2 expression was detected in villous stroma, Hofbauer cells, or endothelial cells. […] We propose one explanation could be the polarized expression of ACE2 away from the maternal blood and pronounced paucity of TMPRSS2 expression in trophoblast.
32742475 The expression of angiotensin-converting enzyme 2 (ACE2), the receptor of SARS-CoV-2, was aberrantly expressed in many tumors. […] In this study, by exploring the TCGA and GTEx public databases, we investigated ACE2 expression and its association with prognosis in non-small cell lung cancer (NSCLC), the most susceptible caner type. […] We found that lung was one of the major organs with highly expressed ACE2. […] Furthermore, ACE2 expression was significantly elevated in lung adenocarcioma (LUAD) and lung squamous cell carcinoma (LUSC) compared to normal tissues. […] DNA methylation might be one possible mechanism leading to ACE2 upregulation. […] Despite that, the AEC2 expression was not statistically associated with disease-free survival (DFS) and overall survival (OS) for LUAD patients, and higher ACE2 expression was associated with prolonged DFS in LUSC patients. […] Taken together, we observed ACE2 was highly expressed in LUAD and LUSC despite the controversial role of ACE2 expression in predicting prognosis in these two common lung cancer types.
32743793 The worsened prognosis of COVID-19 patients with DM can be attributed to a facilitated viral uptake assisted by the host’s receptor angiotensin-converting enzyme 2 (ACE2).
32744436 Single-cell RNA sequencing (scRNA-seq) technology was used to obtain evidence of potential route and ACE2 expressing cell in renal system for underlying pathogenesis of kidney injury caused by COVID-19. […] Ten different clusters were identified and ACE2 was mainly expressed in proximal tubule and glomerular parietal epithelial cells. […] From Gene Ontology (GO) & KEGG enrichment analysis, imbalance of ACE2 expression, renin-angiotensin system (RAS) activation, and neutrophil-related processes were the main issue of COVID-19 leading kidney injury. […] Our study provided the cellular evidence that SARS-Cov-2 invaded human kidney tissue via proximal convoluted tubule, proximal tubule, proximal straight tubule cells, and glomerular parietal cells by means of ACE2-related pathway and used their cellular protease TMPRSS2 for priming.
32745502 Molecular docking is conducted between the predicted top 10 drugs and the virus spike protein/human ACE2. […] The results showed that the above 3 chemical agents have higher molecular binding energies with ACE2.
32745604 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a beta coronavirus that uses the human angiotensin-converting enzyme 2 (ACE2) receptor as a point of entry. […] The present review discusses the origin and structure of the virus and its mechanism of cell entry followed by the therapeutic potentials of strategies directed towards SARS-CoV2-ACE2 binding, the renin-angiotensin system, and the kinin-kallikrein system. […] SARS-CoV2-ACE2 binding-directed approaches mainly consist of targeting receptor binding domain, ACE2 blockers, soluble ACE2, and host protease inhibitors. […] In conclusion, blocking or manipulating the SARS-CoV2-ACE2 binding interface perhaps offers the best tactic against the virus that should be treated as a fundamental subject of future research.
32747012 Angiotensin-converting enzyme 2 (ACE2) can mediate coronavirus entry into host cells.
32747165 Concern about coronavirus 2019 (COVID-19) morbidity and mortality has drawn attention to the potential role of angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) because the SARS-CoV-2 uses the ACE2 receptor as its point of entry into the body.
32748331 It has been reported that SARS-CoV-2 enters into the host cell through interaction between conserved residues of viral spike protein and angiotensin converting enzyme 2 (ACE2) receptor which is highly expressed in host’s cardiac and pulmonary cells and finally transmembrane protease, serine-2 (TMPRSS2), helps in priming of the surface protein.
32750108 There is also evidence linking endothelial cells (ECs) to SARS-CoV-2 infection including: (i) the expression and function of its receptor angiotensin-converting enzyme 2 (ACE2) in the vasculature; (ii) the prevalence of a Kawasaki disease-like syndrome (vasculitis) in COVID-19; and (iii) evidence of EC infection with SARS-CoV-2 in patients with fatal COVID-19.
32750256 Here, we examine human pre-gastrulation embryos to determine the expression patterns of the genes ACE2, encoding the SARS-CoV-2 receptor, and TMPRSS2, encoding a protease that cleaves both the viral spike protein and the ACE2 receptor to facilitate infection. […] Expression of ACE2 and TMPRSS2 in these tissues raises the possibility for vertical transmission and indicates that further work is required to understand potential risks to implantation, placental health and fetal health that require further study.
32750889 Recently, it was confirmed that ACE2 is the receptor of SARS-CoV-2, the pathogen causing the recent outbreak of severe pneumonia around the world. […] It is confused that ACE2 is widely expressed across a variety of organs and is expressed moderately but not highly in lung, which, however, is the major infected organ. […] Here we found that AGTR2 (angiotensin II receptor type 2), a G-protein coupled receptor, has interaction with ACE2 and is highly expressed in lung with a high tissue specificity. […] More importantly, simulation of 3D structure based protein-protein interaction reveals that AGTR2 shows a higher binding affinity with the Spike protein of SARS-CoV-2 than ACE2 (energy: -8.2 vs. -5.1 [kcal/mol]).
32752138 We found that smoking, but not vaping, upregulates ACE2, the cellular receptor that SARS-CoV-2 requires for infection.
32752951 In this study, molecular docking and reactivity were applied for eighteen drugs, which are similar in structure to chloroquine and hydroxychloroquine, the potential inhibitors to angiotensin-converting enzyme (ACE2). […] The reactivity, molecular docking and molecular dynamics were performed for two receptors ACE2 and [SARS-CoV-2/ACE2] complex receptor in two active sites to find a ligand, which may inhibit COVID-19. […] The results obtained from this study showed that Ramipril, Delapril and Lisinopril could bind with ACE2 receptor and [SARS-CoV-2/ACE2] complex better than chloroquine and hydroxychloroquine.
32752979 We suggest that natural selection has favoured a “Don’t burn down the house” strategy, in which free S1 protein may compete with viral particles for the ACE2 receptor, thus reducing the severity of the infection and tissue damage without losing transmission capability.
32753027 C., et al. (2020)) highlights the contribution of a few key point mutations in RBD of spike glycoprotein and molecular basis of its efficient binding with human angiotensin-converting enzyme 2 (ACE2).
32753148 Specifically, SARS-CoV-2 enters the cell via the angiotensin-converting enzyme 2 (ACE2) receptor, which is upregulated in normal pregnancy. […] Upregulation of ACE2 mediates conversion of angiotensin II (vasoconstrictor) to angiotensin-(1-7) (vasodilator) and contributes to relatively low blood pressures, despite upregulation of other components of the renin-angiotensin-aldosterone system. […] As a result of higher ACE2 expression, pregnant women may be at elevated risk for complications from SARS-CoV-2 infection. […] Upon binding to ACE2, SARS-CoV-2 causes its downregulation, thus lowering angiotensin-(1-7) levels, which can mimic/worsen the vasoconstriction, inflammation, and pro-coagulopathic effects that occur in preeclampsia.
32753553 The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds angiotensin-converting enzyme 2 (ACE2) on host cells to initiate entry, and soluble ACE2 is a therapeutic candidate that neutralizes infection by acting as a decoy. […] By using deep mutagenesis, mutations in ACE2 that increase S binding are found across the interaction surface, in the asparagine 90-glycosylation motif and at buried sites. […] The mutational landscape provides a blueprint for understanding the specificity of the interaction between ACE2 and S and for engineering high-affinity decoy receptors. […] Combining mutations gives ACE2 variants with affinities that rival those of monoclonal antibodies.
32753842 It is expected that these similarities (structural and affinity to the receptor of ACE2) can lead to the same pathophysiological activity of the virus by the use of ACE2 and FcγRII (the antibody-dependent enhancement mechanism). […] Therefore, we propose a way of washing out (by plasmapheresis) the possible antibodies against the spike protein of the virus out of patients’ plasma to stop the antibody-dependent enhancement (ADE)-mediated infection of the immune system cells at the first phase of the treatment and simultaneous use of the anti-ACE2 with anti-FcγRII monoclonal antibodies at the second phase.
32754160 Prioritized epitopes were then modeled using linkers and adjuvants, and respective 3D models were constructed to evaluate their physiochemical properties and their possible interactions with ACE2, HLA Superfamily alleles, TLR2, and TLR4.
32754161 The novel 2019 SARS-CoV-2 enters the host cell by binding of the viral surface spike glycoprotein (S-protein) to cellular angiotensin converting enzyme 2 (ACE2) receptor. […] Thereto, high throughput virtual screening approach was used to investigate FDA approved LOPAC library drugs against both the receptor binding domain of spike protein (S-RBD) and ACE2 host cell receptor. […] Evidently, GR 127935 hydrochloride hydrate, GNF-5, RS504393, TNP, and eptifibatide acetate were found binding to virus binding motifs of ACE2 receptor.
32754224 In hub target analysis, the top hub target IL6, and ACE2, the receptor via which SARS-CoV-2 typically enters host cells, were selected for molecular docking analyses, and revealed good binding activities.
32755325 The CB function could be affected by COVID-19-induced inflammatory/immune reactions and/or ACE1/ACE2 imbalance, both at local or systemic level.
32755395 Angiotensin-converting enzyme 2 (ACE2) converts angiotensin II, a potent vasoconstrictor, to angiotensin-(1-7) and is also a membrane protein that enables coronavirus disease 2019 (COVID-19) infectivity. […] AMP-activated protein kinase (AMPK) phosphorylation of ACE2 enhances ACE2 stability. […] This mode of posttranslational modification of ACE2 in vascular endothelial cells is causative of a pulmonary hypertension (PH)-protective phenotype. […] In this study, we investigated whether MDM2 is involved in the posttranslational modification of ACE2 through its ubiquitination of ACE2, and whether an AMPK and MDM2 crosstalk regulates the pathogenesis of PH. […] Bioinformatic analyses were used to explore E3 ligase that ubiquitinates ACE2. […] Cultured endothelial cells, mouse models, and specimens from patients with idiopathic pulmonary arterial hypertension were used to investigate the crosstalk between AMPK and MDM2 in regulating ACE2 phosphorylation and ubiquitination in the context of PH. […] Levels of MDM2 were increased and those of ACE2 decreased in lung tissues or pulmonary arterial endothelial cells from patients with idiopathic pulmonary arterial hypertension and rodent models of experimental PH. […] ACE2-S680L mice (dephosphorylation at S680) showed PH susceptibility, and ectopic expression of ACE2-S680L/K788R (deubiquitination at K788) reduced experimental PH. […] Moreover, ACE2-K788R overexpression in mice with endothelial cell-specific AMPKα2 knockout mitigated PH. […] Maladapted posttranslational modification (phosphorylation and ubiquitination) of ACE2 at Ser-680 and Lys-788 is involved in the pathogenesis of pulmonary arterial hypertension and experimental PH.
32755724 Primary receptor of SARS-CoV-2 is estimated as angiotensin-converting enzyme 2 (ACE2).
32756606 We develop fully glycosylated computational models of ACE2-Fc fusion proteins which are promising targets for a COVID-19 therapeutic. […] We see that some ACE2 glycans interact with the S fragments, and glycans are influencing the conformation of the ACE2 receptor.
32756685 Spike (S) glycoprotein in the SARS-CoV-2 virus is pivotal in understanding the virus anatomy, since it initiates the early contact with the ACE2 receptor in the human cell. […] This provides a pathway to a quantum-chemical understanding of the interaction between the S-protein and the ACE2 receptor with insights into the function of conserved features in the ACE2 receptor binding domain that could inform vaccine and drug development.
32757366 For the placenta-related pathology, we will focus our discussion on the temporal expression of ACE2 throughout gestation for possible propagation of SARS-CoV-2 in the placenta in infected women and ensuing consequences.
32757420 Some authors assumed that smokers have elevated airway expression of ACE2, the cell recognition site of the SARS-Cov-2 spike protein, but this suggestion remains unverified. […] We therefore performed data mining of two independent NCBI GEO genome-wide RNA expression files (GSE7894 and GSE994) and report that in both data sets, current smokers and never smokers have, on average, closely similar bronchial epithelial cell mRNA levels of ACE2, as well as TMPRSS2, coding for a serine protease priming SARS-Cov-2 for cell entry, and ADAM17, coding for a protease implicated in ACE2 membrane shedding.
32757470 Angiotensin-converting enzyme 2 (ACE2) is the functional receptor for SARS-CoV-2. […] In our current study, we found that two types of deficient ACE2 isoforms from different mammals compete with full-length ACE2 for association with S protein. […] One type of ACE2 is a natural soluble isoform, the other type of ACE2 only associates with one loop of the receptor-binding domain (RBD) of the SARS-CoV-2 S protein. […] Mammals with either type of ACE2 will be deficient in support of SARS-CoV-2 entry. […] By combining S recognition and isoform analysis of ACE2, we predict that felids, mustelids, hamsters, and sheep are susceptible to SARS-CoV-2, while canids, swines, cattle, and goats are not permissive for SARS-CoV-2. […] Thus, the differential susceptibilities of mammals with SARS-CoV-2 infection could be partially explained by the ACE2 isoform diversity.
32758569 The protein through virus enters the host cell-human angiotensin-converting enzyme 2 (ACE2) receptor, is also used as a target for molecular docking.
32758869 The viral spike (S) glycoprotein is the key molecule for viral entry through interaction with angiotensin converting enzyme 2 (ACE2) receptor molecules present on the cell membranes. […] Moreover, it has been established that COVID-19 interacts and infects brain cells in humans via ACE2.
32758871 The identification of angiotensin-converting-enzyme 2 (ACE2) as the receptor allowing viral entry to cells precipitated our interest in the role of ACE2 in COVID-19 pathogenesis. […] We propose that COVID-19 is a viral multisystem disease, with dominant vascular pathology, mediated by global reduction in ACE2 function, pronounced in disease conditions with RAS bias toward angiotensin-converting-enzyme (ACE) over ACE2. […] It is further complicated by organ specific pathology related to loss of ACE2 expressing cells particularly affecting the endothelium, alveolus, glomerulus and cardiac microvasculature. […] The possible upregulation in ACE2 receptor expression may predispose individuals with aberrant RAS status to higher viral load on infection and relatively more cell loss. […] Relative ACE2 deficiency leads to enhanced and protracted tissue, and vessel exposure to angiotensin II, characterised by vasoconstriction, enhanced thrombosis, cell proliferation and recruitment, increased tissue permeability, and cytokine production (including IL-6) resulting in inflammation.
32759311 ACE2, an 805-amino acid monocarboxypeptidase type I transmembrane glycoprotein, was discovered in 2000 and has sequence similarity to two other proteins, namely ACE and collectrin. […] The ACE2 gene is located on Xp22 and is highly polymorphic. […] ACE2 is expressed in numerous tissues especially the lung alveolar epithelial cells, heart, kidney and gastrointestinal tract. […] Animal studies have found that ACE2 is central in diseases affecting almost all organ systems, among other cardiac, respiratory, renal and endocrine functions. […] ACE2 was identified as the cellular contact point for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of the global pandemic (COVID-19), and is a potential drug target. […] We describe the genetics and functions of ACE2, explore its various physiological functions in the renin-angiotensin system and discuss its role in the pathophysiology of disease. […] ACE2 opposes the vasopressor ACE pathway of the renin-angiotensin system by converting angiotensin (Ang) I to Ang (1-9) and Ang II to Ang (1-7) which initiates the vasodilatory pathway. […] ACE2 may have a protective effect in the lung and kidney as knockout mice display susceptibility to acute respiratory distress and hypertensive nephropathy.
32759995 The entry of SARS-CoV-2 into host cells is dependent upon angiotensin-converting enzyme 2 (ACE2), which serves as a functional attachment receptor for the viral spike glycoprotein, and the serine protease TMPRSS2 which allows fusion of the viral and host cell membranes. […] We devised a quantitative measure to estimate genetic determinants of ACE2 and TMPRSS2 expression and applied this measure to >2500 individuals. […] Our data show significant variability in genetic determinants of ACE2 and TMPRSS2 expression among individuals and between populations, and indicate a genetic predisposition for lower expression levels of both key viral entry genes in African populations.
32760206 This study focused on the molecular target angiotensin-converting enzyme 2 (ACE2) of SARS-CoV-2 and screened a group of ACE2 agonists by bioinformatics. […] Glucocorticoids are a type of ACE2 activator. […] We verified the efficacy of nine chemicals on regulating ACE2 expression in human GES-1, an upper digestive tract epithelial cell line, and THP-1, a human monocyte cell line, and found that several glucocorticoids imparted activating effects on ACE2 in both cell lines. […] The drugs triciribine and kinetin riboside activate ACE2 expression or inhibit IL-6 production in macrophages to some extent. […] Hydrocortisone showed the strongest effect on ACE2 activation, followed by prednisolone, dexamethasone, and methylprednisolone. […] This study provides experimental and clinical evidence that medium-to-low-dose glucocorticoids may play a protective role in the respiratory and digestive systems by activating ACE2 and suppressing cytokine storm.
32760213 ACE2 expressions in normal tissues, cancers and cell lines were comprehensively assessed. […] Furthermore, we compared ACE2 expression between cancers and matched normal tissues through Gene Expression Profiling Interactive Analysis (GEPIA). […] Finally, the correlations between ACE2 expression and immune infiltration were investigated via Tumor Immune Estimation Resource (TIMER) and GEPIA. […] We found that ACE2 was predominantly expressed in both adult and fetal tissues from the digestive, urinary and male reproductive tracts; moreover, ACE2 expressions in corresponding cancers were generally higher than that in matched healthy tissues. […] GSEA showed that various metabolic and immune-related pathways were significantly associated with ACE2 expression across multiple cancer types. […] Intriguingly, we found that ACE2 expression correlated significantly with immune cell infiltration in both normal and cancer tissues, especially in the stomach and colon.
32761647 The severe acute respiratory syndrome coronavirus-2 (SARS-COV-2), a novel coronavirus responsible for the recent infectious pandemic, is known to downregulate angiotensin-converting enzyme-2 (ACE2). […] SARS-COV-2-induced ACE2 inhibition leads to the augmentation of bradykinin 1-receptor effects, as ACE2 inactivates des-Arg9-bradykinin, a bradykinin metabolite.
32762135 SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). […] As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT1 R) axis associated with oxidative stress.
32762171 Meanwhile, the tissue expression, related pathways and reactome pathways of angiotensis Ⅰ converting enzyme 2 (ACE2) and C-type lectin domain family 4 member M (CLEC4M) receptors were analyzed. […] ACE2 and CLEC4M are expressed in alimentary system, heart, kidney, lung and placenta.
32762417 Recent studies have pointed the role of angiotensin-converting enzyme-II (ACE2) in mediating the entry of SARS-CoV-2 to the host cell by binding to the receptor-binding domain (RBD) of viral spike protein, and successive priming by cellular proteases initiates the infection. […] SARS-CoV replication rate and disease severity is controlled by the binding affinity of RBD with ACE2. […] To understand, how mutations in the conserved residues of RBD affect the molecular interaction with ACE2, we generated five alanine mutants i.e. […] Y449A, N487A, Y489A, N501A and Y505A in the receptor binding motif (RBM) of the ACE2-RBD SARS-CoV-2 complex (PDB: 6M0J). […] In silico mutational analysis revealed loss of important intermolecular hydrogen bonds and other non-bonded contacts, critical for molecular recognition of SARS-CoV-2 RBD to ACE2, which is well supported by saturation mutagenesis study of binding interface residues. […] Global motion analysis through principal component studies revealed that RBD exhibits protuberant in-ward motion towards the human ACE2 binding interface which may be crucial for molecular interaction.
32762537 We chose important proteins from the SARS-CoV-2 genome such as NSP4, NSP15 and RdRp along-with the human ACE2 receptor which is the first point of contact with the virus. […] Limonin which is largely used in traditional Indian medicine system is found to inhibit the human ACE2 receptor (making it inefficient in binding to the receptor binding domain of SARS-CoV-2).
32764120 As highlighted by the current COVID-19 epidemic, caused by the novel coronavirus SARS-CoV-2, similar thinking may apply in imaging viral pathogens; for this case prominent effects on host proteins most notably ACE2 might also provide worthwhile imaging targets.
32764907 The SARS-CoV-2 infection depends on ACE2, TMPRSS2, and CD147, which are expressed on host cells. […] Several studies suggest that some single nucleotide polymorphisms (SNPs) of ACE2 might be a risk factor of COVID-19 infection. […] Genotypes affect ACE2 structure, its serum concentration, and levels of circulating angiotensin (1-7).
32765939 Carnosine is an effective anti-inflammatory agent which can also inhibit CD26 and ACE2 activity.
32768565 The presence of SARS-CoV-2-related viruses in Malayan pangolins, in silico analysis of the ACE2 receptor polymorphism and sequence similarities between the Receptor Binding Domain (RBD) of the spike proteins of pangolin and human Sarbecoviruses led to the proposal of pangolin as intermediary. […] However, the binding affinity of the pangolin ACE2 receptor for SARS-CoV-2 RBD was later on reported to be low.
32768580 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel member of the betacoronaviruses family affecting the lower respiratory tract mainly through binding to angiotensin converting enzyme 2 (ACE2) via its S-protein. […] Genetic analysis of (ACE2) gene revealed several variants that have been suggested to regulate the interaction with S protein. […] The effect of N720D variant on ACE2 structure and thermodynamic stability was studied by DynaMut. […] HDOCK was utilised to model TMPRSS2 protease binding to ACE2 WT and D720 variant cleavage site. […] PRODIGY was used to calculate binding affinities and MD simulation tools calculated the at 100 ns for ACE2 apo structure and the ACE2-TMPRSS2 complex. […] The hotspot N720D variant in the CLD of ACE2 affected the stability and flexibility of ACE2 by increasing the level of motion in the loop region, resulting in a more favourable site for TMPRSS2 binding and cleavage. […] Consequently, this would facilitate S-protein binding and can potentially increase viral entry highlighting the importance of variants affecting the ACE2-TMPRSS2 complex.
32769398 A disintegrin and metalloproteinase 17 (ADAM17), an ectodomain sheddase, is a key component of ACE2 modulation and plays a complex role in inflammation and immunosurveillance.
32769760 In this context, angiotensin-converting enzyme 2 (ACE2), an angiotensin-converting enzyme homologue, has been recognized as a facilitator of viral entry into the host, albeit its involvement in other counter-regulatory effects, such as converting angiotensin (Ang) II into Ang 1-7 with its known protective actions. […] Thus, concern was raised that the use of renin-angiotensin system inhibitors by increasing ACE2 expression may enhance patient susceptibility to the COVID-19 virus. […] Based on these intricate mechanisms, various preventive and therapeutic strategies may be devised, such as upregulating ACE2 and/or using recombinant ACE2, and exploiting the NEP, bradykinin and serine protease pathways, in addition to anti-inflammatory and antiviral therapies.
32770567 The spike glycoproteins of the COVID-19 (similar to SARS-CoV) attach to the angiotensin-converting enzyme (ACE2) and transit over a stabilized open state for the viral internalization to the host cells and propagate with great efficacy. […] Moreover, out of three distinct binding sites (I, II and III) of spike core when HCQ binds only with site III (farthest from the nCoV-RBD of ACE2 contact), epigallocatechin gallate and theaflavin gallate bind all three sites.
32771682 SARS-CoV-2 enters cells by binding of its spike protein to angiotensin-converting enzyme 2 (ACE2). […] Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) have been reported to increase ACE2 expression in animal models, and worse outcomes are reported in patients with co-morbidities commonly treated with these agents, leading to controversy during the COVID-19 pandemic over whether these drugs might be helpful or harmful. […] SARS-CoV-2 hijacks ACE2to invade and damage cells, downregulating ACE2, reducing its protective effects and exacerbating injurious Ang II effects.
32771797 It has been observed that the virus invades human body mainly through binding to angiotensin-converting enzyme 2 (ACE2) receptors similar to SARS-CoV and the main protease (Mpro) acts as a critical protease for digesting the polyprotein into functional polypeptides during the replication and transcription process of 2019-nCoV.
32772343 The results have a potentially great interest in drug discovery since ASCT2 is an acknowledged target of anticancer therapy, and B0AT1 together with ACE2 is part of a receptor for the SARS-Cov-2 RBD proteins.
32773986 Infection by SARS-CoV-2 occurs via the binding of its S protein to the angiotensin-converting enzyme-2 receptor (ACE2-R). […] S binding to ACE2-R leads to a drop in ACE2, a homolog of angiotensin converting enzyme (ACE). […] ACE2 counteracts the damaging effects of ACE on CNS neurons. […] Inactivation of ACE2 following binding of SARS-CoV-2 S protein to ACE2-R in situ might blunt ACE2-moderating effects upon ACE CNS neurotoxicity and neurodegeneration. […] Here, we propose a neurobiological mechanism directly involving SARS-CoV-2 binding to ACE2-R in the etiology of putative Neuro-CoViD-19.
32774170 The sex-prevalent expression of the attachment and permissive molecules ACE2 and TMPRSS2 further supports the concept of a male-oriented vulnerability.
32777054 It is widely known that SARS-CoV-2 uses membrane-bound angiotensin-converting enzyme 2 (ACE2) as a receptor, resulting in internalisation of the complex by the host cell. […] We discuss the evidence that failure to suppress coronaviral replication within 5 days results in sustained downregulation of ACE2 protein expression, and that ACE2 is under negative-feedback regulation. […] We then expose openly-available experimental repository data that demonstrate the gene for ACE2 lies in a novel cluster of interegulated genes on the X chromosome including PIR encoding pirin (quercetin 2,3-dioxygenase), and VEGFD encoding the predominantly lung-expressed vascular endothelial growth factor D. […] Thus for patients who fail to rapidly suppress viral replication, the newly-appreciated ACE2 co-regulated cluster predicts delayed responses that would account for catastrophic deteriorations. […] We conclude that ACE2 homeostatic drives provide a unified understanding which should help optimise therapeutic approaches during the wait until safe, effective vaccines and antiviral therapies for SARS-CoV-2 are delivered.
32778033 Angiotensin converting enzyme 2(ACE2) as a component of the RAS system. […] The major product of ACE2 is Ang1-7, known as a vasodilator peptide and part of the depressant arm of the RAS. […] There are two form of ACE2. […] Coronavirus cover with some proteins in order to help viral attachment to the cell membrane ACE2 as a receptor and then fuse and enter the cells. […] ACE2 was expressed in oral Cavity, salivary glands of the mouth, esophagus, myocardial cells, kidney, and enterocytes, along all the respiratory tract, intestine, and blood vessels. […] We also reviewed the probable mechanism of using ACE2 in viral attachment and the probable treatment processes will also be discussed based on the surface proteins of the virus and ACE2.
32779305 Docking analysis identified lead molecules with favorable binding energy, number of poses and hydrogen bond interactions, which indicates the effective modulation of ACE2 and TMPRSS2 receptors.
32779445 The position of S protein mutations showed they were far from the binding site of this protein with angiotensin-converting enzyme-2 (ACE2) as the host cell receptor.
32779780 Overall, ACE2-binding, post-fusion core, open-state and sub-optimal antibody-binding conformations were preferentially sampled by the G614 mutant, but not wild type.
32779891 Furthermore, COVID-19 may also increase sympathetic discharge, through changes in blood gases (chronic intermittent hypoxia, hyperpnea), Angiotensin-Converting Enzyme (ACE)1/ACE2 imbalance, immune/inflammatory factors or emotional distress.
32780149 Angiotensin converting enzyme 2 (ACE2), a functional receptor for SARS-CoV, now appears likely to mediate 2019-nCoV entry into human cells. […] In this review, we describe the roles performed by ACE2 as an enzymatic catalyst and as a receptor for this novel coronavirus. […] We also summarize the latest research pertaining to the changes noted in ACE2 expression after viral binding, and the relationships relating to virus transmission and population susceptibility to it.
32783136 Our findings highlight that male reproductive tissues could be targeted by SARS-CoV-2, particularly the testis since it co-expresses the receptor (ACE2) and the protease (TMPRSS) needed for viral entry.
32783619 This process may occur due to acquired deficiency of angiotensin-converting enzyme 2 (ACE2), resulting in reduced degradation of ANG II.
32783758 Discovery of ACE2 (angiotensin-converting enzyme 2) revealed that the renin-angiotensin system has 2 counterbalancing arms. […] ACE2 is a major player in the protective arm, highly expressed in lungs and gut with the ability to mitigate cardiopulmonary diseases such as inflammatory lung disease. […] ACE2 also exhibits activities involving gut microbiome, nutrition, and as a chaperone stabilizing the neutral amino acid transporter, B0AT1, in gut. […] But the current interest in ACE2 arises because it is the cell surface receptor for the novel coronavirus, severe acute respiratory syndrome coronavirus-2, to infect host cells, similar to severe acute respiratory syndrome coronavirus-2. […] This suggests that ACE2 be considered harmful, however, because of its important other roles, it is paradoxically a potential therapeutic target for cardiopulmonary diseases, including coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2. […] This review describes the discovery of ACE2, its physiological functions, and its place in the renin-angiotensin system. […] It illustrates new analyses of the structure of ACE2 that provides better understanding of its actions particularly in lung and gut, shedding of ACE2 by ADAM17 (a disintegrin and metallopeptidase domain 17 protein), and role of TMPRSS2 (transmembrane serine proteases 2) in severe acute respiratory syndrome coronavirus-2 entry into host cells. […] Cardiopulmonary diseases are associated with decreased ACE2 activity and the mitigation by increasing ACE2 activity along with its therapeutic relevance are addressed. […] Finally, the potential use of ACE2 as a treatment target in COVID-19, despite its role to allow viral entry into host cells, is suggested.
32784326 The discovery that the virus binds the angiotensin-converting enzyme 2 (ACE2) receptor has led to investigation of the renin-angiotensin system for possible therapeutic targets.
32784543 These patients are also characterized by increased and directly correlated levels of both Angiotensin Converting Enzyme 2 (ACE2) and Ang 1-7. […] Of specific interest are chloroquine/hydroxychloroquine’s ability to inhibit SARS-CoV infection by impairing ACE2, the SARS-CoV2 entry point, through terminal glycosylation via effects on TGN/post-Golgi pH homeostasis. […] We suggest that linkage between the specific gene defects identified in GS and BS and the myriad of distinctive and frequently overlapping clinical findings may be the result of aberrant glycosylation of ACE2 driven by altered TGN/endosome system acidification caused by the metabolic alkalosis brought about by these salt-losing tubulopathies in addition to their altered intracellular calcium signaling due to a blunted second messenger induced intracellular calcium release that is, in turn, amplified by the RAS system.
32784802 Cellular entry of SARS-CoV-2 is thought to occur through the binding of viral spike S1 protein to ACE2. […] The entry process involves priming of the S protein by TMPRSS2 and ADAM17, which collectively mediate the binding and promote ACE2 shedding. […] In this study, microarray and RNA-sequencing (RNA-seq) expression data were utilized to profile the expression pattern of ACE2, ADAM17, and TMPRSS2 in type 2 diabetic (T2D) and non-diabetic human pancreatic islets. […] The expression of ACE2 was significantly increased in diabetic/hyperglycemic islets compared to non-diabetic/normoglycemic. […] Islets from female donors showed higher ACE2 expression compared to males; the expression of ADAM17 and TMPRSS2 was not affected by gender. […] Lastly, ACE2 expression was higher in sorted pancreatic β-cell relative to other endocrine cells. […] In conclusion, ACE2 expression is increased in diabetic human islets. […] More studies are required to investigate whether variations of ACE2 expression could explain the severity of COVID-19 infection-related symptoms between diabetics and non-diabetic patients.
32784826 Moreover, in both case studies, it is interesting to note that COVID-19, ACE2 and FVIII positivity was detected in the same fields.
32784899 Primarily, direct-acting antivirals rely on inhibition of the interaction between ACE2 and the receptor binding domain (RBD) of the Spike (S) protein or targeting the more conserved heptad repeats (HRs), involved in the membrane fusion process.
32785086 There has been much speculation about the potential role of non-steroidal inflammatory drugs (NSAIDs), which increase the expression of angiotensin-converting enzyme 2 (ACE2), a binding target for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to enter the host cell, which could lead to poorer outcomes in COVID-19 disease.
32785121 Further, several natural bioactive compounds interact with the angiotensin-converting enzyme 2 (ACE2) receptor, the gateway for severe acute respiratory syndrome (SARS) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
32786014 The practice of serial passage mimics a natural zoonotic jump, and offers explanations for SARS-CoV-2’s distinctive spike-protein region and its unexpectedly high affinity for angiotensin converting enzyme (ACE2), as well as the notable polybasic furin cleavage site within it.
32786452 It was recently reported that the human receptor angiotensin-converting enzyme 2 (ACE2) plays a key role for capturing SARS-CoV-2 into the human target body, and binding studies were performed using biosensors techniques based on surface plasmon resonance and bio-layer interferometry. […] The published affinity constants for the interactions, derived using the traditional approach, described a single interaction between ACE2 and the SARS-CoV-2 receptor binding domain (RBD). […] This information can prove very useful in providing mechanistic information and insights about the mechanism of interactions between ACE2 and SARS-CoV-2 RBD or similar systems.
32786692 This virus recognizes its receptor, angiotensin-converting enzyme 2 (ACE2), using the receptor binding domain of its spike protein subunit S1. […] Many missense mutations are reported in various human populations for the ACE2 gene. […] In the current study, we predict the affinity of many ACE2 variants for binding to S1 protein using different computational approaches. […] The dissociation process of S1 from some variants of ACE2 is studied in the current work by molecular dynamics approaches. […] We study the relation between structural dynamics of ACE2 in closed and open states and its affinity for S1 protein of SARS-CoV-2.
32786695 This study provides an initial evaluation of current drug candidates from various reports using our systemic in silico drug screening based on structures of viral proteins and human ACE2 receptor.
32786709 Both SARS-CoV-2, initially named 2019-nCoV, and SARS-CoV were reported to utilize angiotensin-converting enzyme 2 (ACE2) as an entry receptor in human cells. […] To better understand the interplay between SARS-CoV-2 and ACE2, we performed computational alanine scanning mutagenesis on the “hotspot” residues at protein-protein interfaces using relative free energy calculations.
32786890 In this work, molecular docking was used to study (in silico) the interaction of 24 ligands, divided into four groups, with four SARS-CoV-2 receptors, Nsp9 replicase, main protease (Mpro), NSP15 endoribonuclease, and spike protein (S-protein) interacting with human ACE2.
32787328 Targeting the binding affinity of molecules for either the isolated SARS-CoV-2 S-protein at its host receptor region or the S-protein:human ACE2 interface complex, we screen ligands from drug and biomolecule data sets that can potentially limit and/or disrupt the host-virus interactions.
32787980 Almost all most-cited publications in this period are related to SARS and the ACE2 protein.
32788194 Infection of 293FT target cells was possible only if the cells were engineered to stably express the human angiotensin-converting enzyme 2 (ACE2) receptor, but stably introducing an additional copy of this receptor did not further enhance susceptibility.
32788312 SARS-CoV-2 primarily targets the lung and enters the body through ACE2 receptors.
32789839 The mechanisms contributing to cardiac disease burden include hypoxemia, inflammatory factor storm, dysfunctional angiotensin converting enzyme 2 (ACE2), and drug-induced cardiac toxicity. […] Notably, the macrophages expressing ACE2 as direct host cells of SARS-CoV-2 secrete chemokine and inflammatory cytokines, as well as a decrease in cellular immune responses to SARS-CoV-2 infection due to elevated exhaustion levels and dysfunctional diversity of T cells, that may be accountable for the “hyperinflammation and cytokine storm syndrome” and subsequently acute cardiac injury and deteriorating cardiovascular disease in COVID-19 patients.
32790205 The possible risk factors of coronavirus disease 2019 (COVID-19) infection on fertility comes from the abundance of angiotensin-Converting Enzyme-2 (ACE2), receptor entry of the virus, on testes, a reduction in important sex hormone ratios and COVID-19-associated fever.
32790406 Experimental studies have revealed that spike proteins of both SARS-CoV-2 and SARS-CoV bind to angiotensin-converting enzyme 2 (ACE2) before entering the cell for replication. […] (Science2020, 367, 1260-1263) showed that the spike protein of SARS-CoV-2 binds to the ACE2 peptidase domain (ACE2-PD) more strongly than does SARS-CoV, and this fact may be associated with a greater severity of the new virus. […] To understand the binding mechnism and experimental results, we investigated how the receptor binding domain (RBD) of SARS-CoV (SARS-CoV-RBD) and SARS-CoV-2 (SARS-CoV-2-RBD) interacts with a human ACE2-PD using molecular modeling. […] Using steered all-atom molecular dynamics simulations, we demonstrate that, like a coarse-grained simulation, SARS-CoV-2-RBD was associated with ACE2-PD more strongly than was SARS-CoV-RBD, as evidenced by a higher rupture force and larger pulling work. […] We show that the binding affinity of both viruses to ACE2 is driven by electrostatic interactions.
32790936 Although conflicting hypotheses on the potential role of nicotine in COVID-19 pathology have recently been offered, we believe that nicotine itself, through its interaction with the nicotinic cholinergic system, as well as ACE2, may not only be of use in a variety of neuropsychiatric and neurodegenerative diseases, but may also be of potential use in COVID-19.
32791255 Coronavirus disease 2019 (COVID-19) is commonly associated with kidney damage, and the angiotensin converting enzyme 2 (ACE2) receptor for SARS-CoV-2 is highly expressed in the proximal tubule cells.
32793181 Moreover, as SARS-CoV-2 Spike-glycoprotein uses human ACE2-receptor for viral entry, targeting the Spike-RBD-ACE2 has been viewed as a promising strategy to control the infection. […] The result shows rilapladib is the only quinoline that can interrupt the Spike-RBD-ACE2 complex.
32793244 SARS-CoV-2 shares similar features with SARS-CoV-1, notably the use of the angiotensin conversion enzyme 2 (ACE2) as a receptor to enter the host cells. […] We also hypothesize that an ACE2-cleaved protein, angiotensin 1-7, has a beneficial action on immune deregulation and that its low expression during the SARS-CoV-2 infection could explain the severity of infection.
32794346 Angiotensin-converting enzyme 2 (ACE2) is the receptor of both SARS-CoV and SARS-CoV-2, but only ACE2s of certain animals can be utilized by the viruses. […] Here, we employed pseudovirus cell-entry assay to evaluate the receptor-utilizing capability of ACE2s of 20 animals by the two viruses and found that SARS-CoV-2 utilized less ACE2s than SARS-CoV, indicating a narrower host range of SARS-CoV-2. […] Especially, SARS-CoV-2 tended not to use murine or non-mammal ACE2s. […] Meanwhile, pangolin-CoV, another SARS-related coronavirus highly homologous to SARS-CoV-2 in its genome, yet showed similar ACE2 utilization profile with SARS-CoV rather than SARS-CoV-2. […] To clarify the mechanism underlying the receptor utilization, we compared the amino acid sequences of the 20 ACE2s and found 5 amino acid residues potentially critical for ACE2 utilization, including the N-terminal 20th and 42nd amino acid residues that might determine the different receptor utilization of SARS-CoV, SARS-CoV-2 and pangolin-CoV.
32795830 The delayed lung damage after SARS-CoV-2 infection may be caused by an autoimmune response to ACE2 induced by forced presentation of the ACE2 protein in a complex with CoV Spike in Fc Receptor positive Antigen Presenting Cells in the lung. […] 1) Autoantibodies and T cells to ACE2 may be found in patients with the lung damage but not in those without 2) There may be an HLA linkage with the delayed lung disease 3) Vaccines based on the spike protein might initiate the process by amplifying Fc mediated uptake of ACE2-Spike complexes into APCs. […] The development of autoantibodies to ACE2 might predict the development of the inflammatory phase of Covid-19 disease. […] It might be wise to consider engineering versions of the spike that no longer bind to ACE2 for inclusion in vaccines.
32796792 SARS-CoV-2, has a high level of sequential similarities to the SARS-CoV-1 and uses the same receptors when it enters the human body (angiotensin-converting enzyme 2/ACE2).
32797326 Limited studies have suggested: (i) no direct interactions between ibuprofen and SARS-CoV-2 and (ii) there is no evidence to suggest ibuprofen affects the regulation of angiotensin-converting-enzyme 2 (ACE2), the receptor for COVID-19, in human studies. […] Furthermore, in vitro studies suggest ibuprofen may facilitate cleavage of ACE2 from the membrane, preventing membrane-dependent viral entry into the cell, the clinical significance of which is uncertain.
32798222 We present a microsphere-based flow cytometry assay that quantifies the ability of plasma to inhibit the binding of spike protein to angiotensin converting enzyme 2 (ACE2). […] Plasma from 22 subjects who recovered from mild Coronavirus disease 2019 (COVID-19) and expressed anti-spike-trimer IgGs inhibited ACE2-spike binding to a greater degree than controls.
32798244 We hypothesized that the observed low incidence of perinatal infection could be related to a low expression of the membrane receptor for SARS-CoV2, ACE2, in the fetal-placental unit. […] We evaluated protein expression of ACE2 both in placentas and fetal organs from non-infected pregnancies across gestation. […] Immunocytochemistry analysis for ACE2 in organs and placentas were performed in May 2020, in samples from a registered biobank. […] Tissues’ sections were incubated with rabbit monoclonal anti-ACE2. […] Protein expression of ACE2 was detected by immunochemistry. […] ACE2 expression was detected in fetal kidneys, rectum and ileum across gestation and similarly in the pediatric control. […] In the pediatric control, ACE2 was only detectable in type 2 pneumocytes. […] No ACE2 expression was found in the cerebral ependymal, parenchyma nor in cardiac tissues ACE2 was expressed in syncitiotrophoblast and cytotrophoblast from 7th weeks’ onwards and across gestation but not in the amnion. […] Similar intensity and distribution of ACE2 staining were identified in the mother’s SARS-CoV2 placenta. […] Marked placental expression of ACE2 provides a rationale for vertical transmission at cellular level. […] Absence of ACE2 expression in the fetal brain and heart is reassuring on the risk of congenital malformation.
32798445 Immunization of mice with VSV-eGFP-SARS-CoV-2 elicits high antibody titers that neutralize SARS-CoV-2 and target the receptor binding domain that engages human angiotensin-converting enzyme-2 (ACE2). […] Upon challenge with a human isolate of SARS-CoV-2, mice that expressed human ACE2 and were immunized with VSV-eGFP-SARS-CoV-2 show profoundly reduced viral infection and inflammation in the lung, indicating protection against pneumonia.
32799423 Of 59 tested medications, 56% modified ACE2 expression, whereas 24% modified TMPRSS2 expression. […] ACE2 was increased with only a few of the tested medication groups, namely the renin-angiotensin inhibitors, such as enalapril, antibacterial agents, such as nitrofurantoin, and the proton pump inhibitor, omeprazole. […] The majority of the other medications decreased ACE2 expression to variable degrees with allopurinol and cisplatin causing the most noticeable downregulation. […] The prolonged exposure to combinations of these medications could regulate the expression of ACE2 and TMPRSS2 in a way that may affect kidney susceptibility to SARS-CoV-2 infection. […] Data presented here suggest that we should be vigilant about the potential effects of commonly used medications on kidney tissue expression of ACE2 and TMPRSS2.
32802131 The intersection between the AHI component proteins and angiotensin-converting enzyme 2 (ACE2) coexpression proteins was analyzed. […] Between AHI targets and ACE2 coexpression proteins, 26 common proteins were obtained.
32802980 First, we collect assay data for 65 target human proteins known to interact with the SARS-CoV-2 proteins, including the ACE2 receptor.
32804015 We have developed a new class of tetravalent, biparatopic therapy, 89C8-ACE2. […] It combines the specificity of a monoclonal antibody (89C8) that recognizes the relatively conserved N-terminal domain of the viral Spike (S) glycoprotein, and the ectodomain of ACE2, which binds to the receptor-binding domain of S. […] This molecule shows exceptional performance in vitro, inhibiting the interaction of recombinant S1 to ACE2 and transduction of ACE2-overexpressing cells by S-pseudotyped lentivirus with IC50s substantially below 100 pM, and with potency approximately 100-fold greater than ACE2-Fc itself. […] Moreover, 89C8-ACE2 was able to neutralize authentic viral infection in a standard 96-h co-incubation assay at low nanomolar concentrations, making this class of molecule a promising lead for therapeutic applications.
32805314 There is no notable induction of IFNs and IFN-induced ACE2, significant receptor responsible for S-protein binding mediated viral entry.
32806067 The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein plays a crucial role in binding the human cell receptor ACE2 that is required for viral entry. […] Many studies have been conducted to target the structures of RBD-ACE2 binding and to design RBD-targeting vaccines and drugs. […] Nevertheless, mutations distal from the SARS-CoV-2 RBD also impact its transmissibility and antibody can target non-RBD regions, suggesting the incomplete role of the RBD region in the spike protein-ACE2 binding. […] Here, in order to elucidate distant binding mechanisms, we analyze complexes of ACE2 with the wild-type spike protein and with key mutants via large-scale all-atom explicit solvent molecular dynamics simulations. […] We find that though distributed approximately 10 nm away from the RBD, the SARS-CoV-2 polybasic cleavage sites enhance, via electrostatic interactions and hydration, the RBD-ACE2 binding affinity. […] We find that the tetrapeptide GluGluLeuGlu binds to one of the three polybasic cleavage sites of the SARS-CoV-2 spike protein lessening by 34% the RBD-ACE2 binding strength. […] This significant binding energy reduction demonstrates the feasibility to neutralize RBD-ACE2 binding by targeting this specific polybasic cleavage site. […] Our work enhances understanding of the binding mechanism of SARS-CoV-2 to ACE2, which may aid the design of therapeutics for COVID-19 infection.
32806657 Virus entry occurs via binding the angiotensin-converting enzyme 2 (ACE2) receptor present in almost all tissues and organs through the Spike (S) protein.
32807895 Recent studies have shown that, similarly to SARS-CoV, SARS-CoV-2 utilises the Spike glycoprotein on the envelope to recognise and bind the human receptor ACE2. […] We combined and integrated docking simulations, with molecular dynamics (MD), Supervised MD (SuMD) and Steered MD (SMD) simulations to identify a Spike protein - ACE2 interaction inhibitor. […] Our data showed that Simeprevir and Lumacaftor bind the receptor-binding domain of the Spike protein with high affinity and prevent ACE2 interaction.
32808185 Angiotensin-converting enzyme 2 (ACE2) and Transmembrane serine protease (TMPRSS2) are the main cell entry receptors of SARS-CoV-2. […] Within the analgesics, acetaminophen revealed a dose-dependent reduction in expression of ACE2, while non-steroidal anti-inflammatory drugs had mixed effect on receptors expression. […] To confirm the observed effects on primary human hepatocytes, rat hepatocyte treatments data was obtained from DrugMatrix toxicogenomic database (GSE57805), which showed a similar ACE2 and TMPRSS2 expression pattern. […] Treatment of common co-morbidities often require chronic use of multiple medications, which may result in an additive increase in the expression of ACE2 and TMPRSS2.
32808850 We also outline the emerging imaging techniques, such as the RNAscope, which might also aid in our understanding of the significance of COVID-19-specific biomarkers, such as the angiotensin-converting enzyme 2 (ACE2) cellular receptor.Overall, great progress has been made in COVID-19 research in a short period.
32809116 In this paper, we also review the pathogenesis of SARS-CoV-2 infection and how it worsens CVD and postulate that the differences in modulation of the renin-angiotensin-aldosterone system (RAAS) axis which controls angiotensin-converting enzyme (ACE)/ACE2 balance may be an important determinant of COVID-19 outcomes in Africa.
32810867 Recent research has confirmed the role of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) as key host-specific cellular moieties responsible for the cellular entry of the virus. […] Accordingly, the ongoing medical examinations and the autopsy reports of the deceased individuals indicate that organs/tissues with high expression levels of ACE2, TMPRSS2 and other putative viral entry-associated genes are most vulnerable to the infection. […] Co-expression analysis of ACE2 and TMPRSS2 and protein-protein interaction among the host and viral proteins elected regulatory cytoskeleton protein-enriched SUSs as the most vulnerable cell type of the olfactory epithelium. […] Furthermore, expression, structural and docking analyses of ACE2 revealed the potential risk of olfactory dysfunction in four additional mammalian species, revealing an evolutionarily conserved infection susceptibility.
32811230 The currently known receptor for the virus, ACE2, regulates the renin-angiotensin system and is increased during pregnancy.
32813238 Current clinical studies have interpreted that angiotensin-converting enzyme 2 (ACE2) is the host receptor for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). […] In addition, ACE2 is the major component of the renin-angiotensin system. […] ACE2 deteriorates angiotensin II, a peptide that is responsible for the promotion of stroke. […] The downregulation of ACE2 further activates an immunological cascade. […] Human ACE2 expression level and pattern in various tissues might be decisive for the vulnerability, symptoms, and treatment outcomes of the SARS-CoV-2 infection. […] As the SARS-CoV-2 binds to ACE2, it will hamper the activity of ACE2 in providing neuroprotection, especially in the case of stroke patients. […] Due to the downregulation of ACE2, the inflammatory response is activated in the ischemic penumbra.
32814566 Next, it examines the influence of hypoxia on upregulation of ACE2 (target receptor for SARS-CoV-2 entry) expression, with supporting transcriptomic analysis of a publicly available gene expression profile dataset of human renal proximal tubular epithelial cells cultured in normoxic or hypoxic conditions.
32814791 Notably, residues of receptor-binding domain (RBD) showing crucial interactions with angiotensin-converting enzyme 2 (ACE2) and cross-reacting neutralizing antibody were found to be conserved among the analyzed virus strains, except for replacement of lysine with arginine at 378th position of the cryptic epitope of a Shanghai isolate, hCoV-19/Shanghai/SH0007/2020 (EPI_ISL_416320).
32815593 In this article, the relationship between the Adrenergic system and the renin-angiotensin-aldosterone system (RAAS) is focused in COVID-19 and a vicious circle consisting of the Adrenergic system-RAAS-Angiotensin converting enzyme 2 (ACE2)-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (which is referred to as the “ARAS loop”) is proposed. […] Beta-adrenergic blockers may decrease the SARS-CoV-2 cellular entry by decreasing ACE2 receptors expression and cluster of differentiation 147 (CD147) in various cells in the body.
32816230 To review the data regarding the expression of angiotensin converting enzyme-2 (ACE2) and transmembrane protease serine-2 (TMPRSS2) in head and neck tissue. […] Scopus, Cochrane Library, Medrxiv, Google Scholar and PubMED/MEDLINE were searched by four independent investigators for studies investigating ACE2 or TMPRSS2 expressions in head and neck tissues. […] ACE2 and TMPRSS2 were expressed in oral, pharyngeal, sinusonasal human mucosa. […] The following cell types expressed ACE2: basal, apical, goblet, minor salivary, and endothelial cells. […] ACE2 and TMPRSS2 were found in the olfactory region, especially in sustentacular non-neural and neural stem cells. […] Animal studies suggested that ACE2 expression may vary regarding age. […] There was an important heterogeneity between studies in the methods used to detect ACE2 and TMPRSS2, leading to a potential identification bias. […] The SARS-CoV-2 receptors, ACE2 and TMPRSS2, are both expressed in many head and neck tissues, enabling the viral entry into the host organism.
32818075 Angiotensin-converting enzyme 2 (ACE2) was reported to be the receptor for SARS-CoV-2. […] We investigated the digestive symptoms of 48 patients with COVID-19 and explored ACE2 expression in digestive tract and lung cancers, based on a series of bulk and single-cell RNA sequencing data obtained from public databases. […] The bulk tissue RNA sequencing analysis indicated that digestive tract organs had higher ACE2 expression levels compared to the lung, and the expression of ACE2 in the lung increased with age. […] Single-cell RNA-Seq results showed that the ACE2-positive-cell ratio in digestive tract organs was significantly higher compared to the lung. […] ACE2 expression was higher in tumor cells compared to normal control (NC) tissues. […] While in gastric tissues, ACE2 expression gradually increased from chronic gastritis to metaplasia, to early cancer.
32818261 The spike (S) glycoprotein binds ACE2 and promotes SARS-CoV-2 entry into host cells.
32818905 Angiotensin converting enzyme 2 (ACE2) is essential to COVID-19 pathogenesis, as the binding of SARS-CoV-2 spike protein (S protein) is required for viral entry and development of COVID-19. […] ACE2 regulates the protective arm of the renin-angiotensin-aldosterone system (RAAS) that endows anti-hypertensive and anti-inflammatory effects in the cardiovascular and pulmonary systems. […] Preclinical data suggest ACE2 might be downregulated after SARS-CoV-2 binding, and treatments that increase ACE2 may prevent cardiopulmonary injury. […] Development, testing, and mass production of novel ACE2 therapies may take years, whereas more effective treatments for COVID-19 are needed urgently. […] Metformin is a widely available anti-diabetic agent that has an excellent safety profile, and clinical and preclinical data suggest metformin may offer cardiopulmonary protection in COVID-19 via enhanced ACE2 expression.
32820179 In silico analyses on the spike protein structure suggests that the mutation is most likely neutral to protein function as it relates to its interaction with the human ACE2 receptor.
32820236 In animal experiments, angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs) are reported to suppress the downregulation of angiotensin converting enzyme 2 (ACE2), and they may inhibit the worsening of pathological conditions.
32820884 Coronaviruses can infect neurons and glial cells through angiotensin-converting enzyme 2 (ACE2) receptors or by endocytosis.
32821757 Recently, Angiotensin-Converting Enzyme-2 (ACE2) has gained some attention for its discovery as a potential attachment target of COVID-19. […] We reviewed the most recent evidence regarding ACE2 distribution and action, the binding mechanism of COVID-19 and its correlation to cellular injury, ACE2 polymorphisms and its association to fatal COVID-19 and susceptibility and, finally, current ACE2-based pharmacotherapies against COVID-19. […] Blocking the ACE2 receptor-binding domain (RBD) using a specific ligand can prevent COVID-19 from binding, and consequently cellular entry and injury. […] Comparatively, soluble ACE2, which has a higher affinity to COVID-19, can neutralize COVID-19 without affecting the homeostatic function of naturally occurring ACE2. […] Lastly, ACE2 mutations and their possible effect on the binding activity of COVID-19 may enable researchers to identify high-risk groups before they become exposed to COVID-19. […] ACE2 represents a promising target to attenuate or prevent COVID-19 associated cellular injury.
32821883 ACE2, the entry receptor of SARS-CoV-2, has been identified in the oral epithelium; however, it is unclear at what developmental stage ACE2 expression emerges and whether ACE2 is expressed in taste buds. […] We found that robust ACE2 expression was observed in the newborn oral epithelium. […] In contrast, only extremely low levels, if any, of ACE2 transcripts in the embryonic stage oral tissue were found (E12.5 and E14.5). […] ACE2 was enriched in a subpopulation of epithelial cells in the basal region of nongustatory filiform papillae but not in the taste papillae or taste buds. […] Expression of ACE2 was detected in a small proportion of type III taste cells.
32822426 Viral entry into the host cell is a multistep process in which SARS-CoV-2 utilizes the receptor-binding domain (RBD) of the spike (S) glycoprotein to recognize angiotensin-converting enzyme 2 (ACE2) receptors on the human cells; this initiates host-cell entry by promoting viral-host cell membrane fusion through large-scale conformational changes in the S protein.
32823591 While SARS-CoV-2 uses angiotensin converting enzyme 2 (ACE2) as the receptor for cell entry, it is important to examine other potential interactions between the virus and other cell receptors.
32824674 High testosterone levels could upregulate transmembrane serine protease 2 (TMPRSS2), facilitating the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into host cells via angiotensin-converting enzyme 2 (ACE2).
32824830 The coronavirus pandemic raging worldwide since December 2019 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which invades human cells via the angiotensin-converting enzyme 2 (ACE2) receptor. […] Although it has already been identified in many organs, ACE2 expression remains largely unknown in the head and neck (HN) sphere. […] We compared ACE2 immunohistochemical expression between 70 paraffin-embedded specimens with two different antibodies and reported the quantified expression in each histological location. […] Surprisingly, we obtained different results depending on the antibody, an absence of labeling having been observed with a monoclonal antibody raised against the extracellular domain, whereas the polyclonal, against the cytoplasmic part of the protein, revealed enriched ACE2 expression, particularly in sinuses, vocal cords, salivary glands and oral cavity epithelial cells. […] In conclusion, this study provides possible routes of entry for the SARS-CoV-2 in HN region and, above all, has led us to encourage caution when studying the ACE2 expression which is currently at the center of all attention.
32825063 Despite high sequence similarity and utilization of common host-cell receptor, human angiotensin-converting enzyme-2 (ACE2) for virus entry, SARS-CoV-2 is much more infectious than SARS-CoV.
32825305 The virus infects human cells by binding of the virus spike to the cell receptor ACE2. […] The crystal structure of SARS-CoV-2 spikes in complex with human ACE2 has recently been solved, and the main amino acid residues involved in the virus-receptor complex have been detected. […] To investigate the affinity of ACE2 of lagomorphs to the SARS-CoV-2 spike, ACE2 sequences from rabbits and American pikas were compared with human ACE2 and with ACE2 from mammals with different susceptibility to the virus. […] Models of the complex formed by SARS-CoV-2 spike and ACE2 from lagomorphs and from other mammals were created for comparative studies. […] ACE2 of lagomorphs showed fewer substitutions than human ACE2 in residues involved in the ACE2-SARS-CoV-2 spike complex, similar to cats. […] Analysis of the binding interface of the simulated complexes ACE2-SARS-CoV-2 spike showed high affinity of the ACE2 of lagomorphs to the viral spike protein. […] These findings suggest that the spike of SARS-CoV-2 could bind the ACE2 receptor of lagomorphs, and future studies should investigate the role of lagomorphs in SARS-CoV-2 epidemiology.
32825469 The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor, angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), and furin, which promote entry of the virus into the host cell, have been identified as determinants of SARS-CoV-2 infection. […] Immunohistochemical analyses showed that ACE2 was expressed in the stratified squamous epithelium of the dorsal tongue and gingiva. […] ACE2, TMPRSS2, and furin mRNA expression was observed in taste bud-derived cultured cells, which was similar to the immunofluorescence observations.
32825954 The main mechanisms of virus internalization and interaction with the host are down-regulation or upregulation of the ACE2 receptor, the surface glycoprotein competition mechanism for the binding of porphyrin to iron in heme formation as well as interference with the immune system.
32825963 As Angiotensin-Converting Enzyme 2 (ACE2) is one of the potential target receptors for SARS-CoV-2 in human body, which is expressed in different tissues, multiple organs might become affected.
32826334 The main receptor of SARS-CoV-2, angiotensin I converting enzyme 2 (ACE2), is now undergoing extensive scrutiny to understand the routes of transmission and sensitivity in different species. […] Here, we utilized a unique dataset of ACE2 sequences from 410 vertebrate species, including 252 mammals, to study the conservation of ACE2 and its potential to be used as a receptor by SARS-CoV-2. […] We designed a five-category binding score based on the conservation properties of 25 amino acids important for the binding between ACE2 and the SARS-CoV-2 spike protein. […] We employed a protein structural analysis to qualitatively assess whether amino acid changes at variable residues would be likely to disrupt ACE2/SARS-CoV-2 spike protein binding and found the number of predicted unfavorable changes significantly correlated with the binding score. […] In addition, we found significant signals of selection and accelerated evolution in the ACE2 coding sequence across all mammals, and specific to the bat lineage.
32826650 Using immunohistochemistry, the samples were tested for the expression of angiotension-converting enzyme 2 (ACE2), dendritic cell-specific intracellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN), DC-SIGN-related protein (DC-SIGNR), and transmembrane serine protease 2 (TMPRSS2). […] In all specimens, both ACE2 and TMPRSS2 were expressed throughout the surface epithelium (corneal, limbal, and conjunctival) and corneal endothelium. […] In corneal stromal cells, ACE2 was sporadically expressed, whereas TMPRSS2 was absent. […] Four specimens expressed DC-SIGN/DC-SIGNR in a similar distribution to ACE2, but 1 specimen from a young donor showed no expression of DC-SIGN/DC-SIGNR. […] ACE2, TMPRSS2, and DC-SIGN/DC-SIGNR were all expressed in the cultured corneal, limbal, and conjunctival epithelial cells. […] Both corneal and conjunctival epithelia express ACE2, DC-SIGN/DC-SIGNR, and TMPRSS2, suggesting that the ocular surface is a potential route for the transmission of SARS-CoV-2. […] The risk of viral transmission with corneal transplantation cannot be ruled out, given the presence of ACE2 in corneal epithelium and endothelium.
32826754 ACE2 mRNA is expressed by a subset of nociceptors that express MRGPRD mRNA, suggesting that SARS-CoV-2 may gain access to the nervous system through entry into neurons that form free nerve endings at the outermost layers of skin and luminal organs.
32826914 MAb362 binds to both SARS-CoV and SARS-CoV-2 spike proteins and competitively blocks ACE2 receptor binding, by overlapping the ACE2 structural binding epitope. […] Furthermore, MAb362 IgA neutralizes both pseudotyped SARS-CoV and SARS-CoV-2 in 293 cells expressing ACE2.
32827525 SARS-CoV-2 viral load, ACE2 RNA levels, and serology for SARS-CoV-2 were quantified.
32828084 Spike (S) glycoproteins on the viral membrane bind to ACE2 receptors on the host cell membrane and initiate fusion, and S protein is currently among the primary drug target to inhibit viral entry. […] Because RBD-ACE2 binding is compatible with the semi-open state, but not with the closed state of the S protein, we propose that the formation of the intermediate state is a prerequisite for the host cell recognition.
32828990 The binding site to the human ACE2 protein as virus receptor and human antibody CR3022 binding site on the spike glycoprotein are rather variable by the criteria used in the present and preceding studies.
32829257 This ability for host switching and interspecies infection is often attributed to the great diversity of these viruses, which is a result of viral and host factors such as the low fidelity of their RNA-dependent RNA polymerase, the high frequency of their homologous RNA recombination, and the adaptation of the S protein to bind host receptors like the angiotensin converting enzyme 2 (ACE2) in the case of SARS-CoV and SARS-CoV-2, and dipeptidyl peptidase 4 (DDP4) in MERS-CoV.
32831104 The outbreak of coronavirus disease (COVID-19) was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), through its surface spike glycoprotein (S-protein) recognition on the receptor Angiotensin-converting enzyme 2 (ACE2) in humans. […] However, it remains unclear how genetic variations in ACE2 may affect its function and structure, and consequently alter the recognition by SARS-CoV-2. […] We have systemically characterized missense variants in the gene ACE2 using data from the Genome Aggregation Database (gnomAD; N = 141,456). […] We further analyzed the structural flexibility of ACE2 and its protein-protein interface with the S-protein of SARS-CoV-2 using our developed Legion Interfaces Analysis (LiAn) program. […] Here, we characterized a total of 12 ACE2 putative deleterious missense variants. […] Of those 12 variants, we further showed that p.His378Arg could directly weaken the binding of catalytic metal atom to decrease ACE2 activity and p.Ser19Pro could distort the most important helix to the S-protein. […] We provide strong evidence of putative deleterious missense variants in ACE2 that are present in specific populations, which could disrupt the function and structure of ACE2. […] These findings provide novel insight into the genetic variation in ACE2 which may affect the SARS-CoV-2 recognition and infection, and COVID-19 susceptibility and treatment.
32831324 To determine the susceptibility of the skin to SARS-CoV-2 infection based on the expression of viral entry factors ACE2 and TMPRSS2 in this organ. […] A comprehensive analysis of human tissue gene expression databases was carried out looking for the presence of the ACE2 and TMPRSS2 genes in the skin. mRNA expression of these genes in skin-derived human cell lines was also assessed. […] The analyses showed high co-expression of ACE2 and TMPRSS2 in the gastrointestinal tract and kidney, but not in the skin. […] Only the human immortalized keratinocyte HaCaT cell line expressed detectable levels of ACE2, and no cell line originating in the skin expressed TMPRSS2.
32831326 ACE2, CD147 and TMPRSS2 receptors expression could indicate poorly explored potential infection targets.
32832038 ACE2 plays a critical role in SARS-CoV-2 infection to cause COVID-19 and SARS-CoV-2 spike protein binds to ACE2 and probably functionally inhibits ACE2 to aggravate the underlying diseases of COVID-19.
32833435 SARS-CoV-2 host cell entry is mediated by the interaction of the viral transmembrane spike glycoprotein (S-protein) with the angiotensin-converting enzyme 2 gene (ACE2), an essential counter-regulatory carboxypeptidase of the renin-angiotensin hormone system that is a critical regulator of blood volume, systemic vascular resistance, and thus cardiovascular homeostasis. […] Accordingly, this work reports an atomistic-based, reliable in silico structural and energetic framework of the interactions between the receptor-binding domain of the SARS-CoV-2 S-protein and its host cellular receptor ACE2 that provides qualitative and quantitative insights into the main molecular determinants in virus/receptor recognition. […] In particular, residues D38, K31, E37, K353, and Y41 on ACE2 and Q498, T500, and R403 on the SARS-CoV-2 S-protein receptor-binding domain are determined as true hot spots, contributing to shaping and determining the stability of the relevant protein-protein interface. […] Overall, these results could be used to estimate the binding affinity of the viral protein to different allelic variants of ACE2 receptors discovered in COVID-19 patients and for the effective structure-based design and development of neutralizing antibodies, vaccines, and protein/protein inhibitors against this terrible new coronavirus.
32834306 After the acute phase of the health crisis, when activity was drastically reduced, cycles have resumed, guided by the recommendations of scientific societies.In this article, a review is presented of all the published information regarding the virus and the reproductive system, pointing out the presence of angiotensin-converting enzyme 2 (ACE2) in the female and male reproductive system, at the testicular, ovarian, endometrial and embryonic levels.
32834430 Both coronaviruses also share the same cellular receptor, which is the angiotensin-converting enzyme 2 (ACE2) one.
32834893 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent for COVID-19, enters host cells via angiotensin-converting enzyme 2 (ACE2) and depletes ACE2, which is necessary for bradykinin metabolism. […] The depletion of ACE2 results in the accumulation of des-Arg (9)-bradykinin and possible bradykinin, both of which bind to bradykinin receptors and induce vasodilation, lung injury, and inflammation.
32834922 These ten well-characterized drugs, previously used to treat malaria and Ebola infections, were screened based on their interactions with the SARS-CoV-2 ACE2 receptor and 3C-like protease.
32835083 Third, nearly 1033 medicinal herbal compounds were collected and docked with ACE2, TMPRSS2, GRP78, and AT1R receptors, which were the most noticeable receptors in causing the COVID-19.
32835126 SARS-CoV-2 binding to angiotensin-converting enzyme 2 (ACE2) receptor is a critical step mediate virus entry into target cells. […] Articles have alluded that the level of ACE2 gene expression in adipose tissue is higher than lung tissue, but a PubMed search found no results in articles to demonstrate this. […] The aim of this study was to investigate ACE2 gene expression in adipose tissue and lung tissue using a public database. […] A search of a public gene expression database to investigate ACE2 gene expression in human tissues. […] ACE2 gene expression was present in both visceral and subcutaneous adipose tissues. […] The gene expression profile demonstrated that ACE2 gene expression was higher in human visceral and subcutaneous adipose tissues than human lung tissue. […] This study demonstrates that ACE2 gene expression is higher in visceral and subcutaneous adipose tissue than that in lung tissue, a major target tissue affected by SARS-CoV-2 infection.
32835302 These include peptides that are contained within evolutionarily divergent regions of the spike protein reported to increase infectivity through increased binding to the ACE2 receptor and within a newly evolved furin cleavage site thought to increase membrane fusion.
32835305 Microscopy and RNA sequencing demonstrate that SARS-CoV-2 can enter hiPSC-CMs via ACE2. […] SARS-CoV-2 infection activates innate immune response and antiviral clearance gene pathways, while inhibiting metabolic pathways and suppressing ACE2 expression.
32835700 The allelic frequencies of the polymorphisms in the ACE2, TMPRSS2, TMPRSS11A, cathepsin L (CTSL), and elastase (ELANE) genes were obtained in four populations from the American, African, European, and Asian continents reported in the 1000 Genome Project. […] Furthermore, forty-eight polymorphisms with possible functional consequences were detected in the non-coding sequences of the following genes: three in ACE2, seventeen in TMPRSS2, ten in TMPRSS11A, twelve in ELANE, and six in CTSL.
32837036 SARS-CoV-2 tends to utilize Angiotensin-converting enzyme 2 (ACE2) of various mammals. […] The imbalance between ACE/Ang II/AT1R pathway and ACE2/Ang(1-7)/Mas receptor pathway in the renin-angiotensin system leads to multi-system inflammation.
32837189 The researchers supporting the use of these medications believe ACE2 functional blockers may block cellular entry of the SARS-CoV-2 virus and thus improve patient outcomes. […] The counter viewpoint argues that continuous use of these drugs results in hyperexpression of ACE2 receptors on respiratory epithelium allowing easier SARS-CoV-2 intracellular entry, resulting in enhanced viral replication and tissue damage.
32837211 The ACE2 enzyme intrinsically involved in the physiology of cardiac function and in the development of hypertension and diabetes has been identified as a functional receptor for SARS-CoV-2.
32837460 Both SARS-CoV and SARS-CoV-2 has a high degree of genetic similarity and bind to the same host cell ACE2 receptor.
32837527 This perspective review gives particular attention to the potential diagnostic testing of the virus in semen and seminal fluids due to its high levels of angiotensin converting enzyme 2 (ACE2) precursor. […] Additional hypothesis is that since ACE2 could serve as a mediator for the endocytosis of the previously SARS coronavirus, SARS-CoV-2 may enter the cells through similar mechanism. […] From the protein expression atlas, high levels of ACE2 precursor were found in intestines and testis.
32837536 This novel virus acquired the ability to infect human cells using the SARS-CoV cell receptor hACE2. […] Because of this, it is essential to improve our understanding of the evolutionary dynamics surrounding the SARS-CoV-2 hACE2 interaction. […] With this analysis, we determine a region inside the receptor-binding domain with putative sites under positive selection interspersed among highly conserved sites, which are implicated in structural stability of the viral spike protein and its union with human receptor ACE2. […] Next, to gain further insights into factors associated with recognition of the human host receptor, we performed modeling studies of five different betacoronaviruses and their potential binding to hACE2.
32837754 Angiotensin-converting enzyme 2 (ACE2) is the receptor of both severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2. […] In order to investigate the potential risk of SARS-CoV-2 vertical transmission, we explored ACE2 and transmembrane protease serine 2 (TMPRSS2) expression patterns in peri-implantation embryos and the maternal-fetal interface using previously published single-cell transcriptome data. […] The results show that day 6 (D6) trophectoderm cells (TE) in peri-implantation embryos, as well as syncytiotrophoblast (STB) at 8 weeks of gestation (STB_8W) and extravillous trophoblasts cells (EVT) at 24 weeks of gestation (EVT_24W) in the maternal-fetal interface, strongly co-expressed ACE2 and TMPRSS2, indicating SARS-CoV-2 infection susceptibility. […] The ACE2 positive-expressing cells in the three cell types mentioned above are found to share common characteristics, which are involved in autophagy and immune-related processes. […] ACE2 showed no gender bias in post-implantation embryos but showed a significant gender difference in D6_TE, D6 primitive endoderm cells (PE), and ACE2 positive-expressing STBs.
32837764 Great attention is also being posed on the potential beneficial/harmful role of angiotensin converting enzyme (ACE) inhibitors, as far as the virus binds to ACE2 to infect cells, but evidences lack.
32837913 Also, angiotensin conversion enzyme 2 (ACE2) plays a highly important role in cellular entry for SARS-CoV-2 and male genital system presents high ACE2 expression.
32837954 Virtual screening was then performed for the 18 selected drugs with ACE2, 3CLpro and PLpro and HR1 and TMPRSS2.
32837985 This pseudovirus contains a Luc reporter gene that enabled us to easily quantify virus entry into angiotensin-converting enzyme 2 (ACE2)-expressing 293T cells. […] Cathepsin (Cat)B/L inhibitor E-64d could significantly block SARS-CoV-2 pseudovirus infection in 293T-ACE2 cells. […] Furthermore, the SARS-CoV-2 spike pseudotyped virus could be neutralized by sera from convalescent COVID-19 patients or recombinant ACE2 with the fused Fc region of human IgG1.
32838074 Using serial analysis of myocardial gene expression employing endomyocardial biopsy starting material in a dilated cardiomyopathy cohort, we show that mRNA expression of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) cardiac myocyte receptor ACE2 is up-regulated with remodeling and with reverse remodeling down-regulates into the normal range. […] Up-regulation in ACE2 in remodeled left ventricles may explain worse outcomes in patients with coronavirus disease 2019 who have underlying myocardial disorders, and counteracting ACE2 up-regulation is a possible therapeutic approach to minimizing cardiac damage.
32838164 Its receptors are angiotensin-converting enzyme 2 (ACE2), and the C-terminal S2 membrane anchoring protein is responsible for translocating the virus into the cell. […] By exploring the theoretical analysis of PCs and ACE2 in COVID-19 cardiovascular susceptibility, some insights on how to prevent and alleviate adverse cardiovascular prognosis have been provided in this study.
32838280 The SARS-CoV-2 coronavirus gains entry to target cells via the angiotensin-converting enzyme 2 (ACE2) receptor present on cells in blood vessels, lungs, heart, intestines, and kidneys. […] Plasma levels of RAS-related proteins (ACE2, Renin and Angiotensinogen (AGT)) were determined by Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement. […] ACE2 levels were lower in PCOS (p < 0.05), suggesting that PCOS women are at risk for development of hypertension.
32838282 It was reviewed that therapeutics targeting SARS-CoV-2 binding to ACE2 receptor, viral RNA synthesis and replication, 3CLpro, RdRp, and helicase will play a crucial role in the development of treatment for SARS-CoV-2 infection.
32838301 Angiotensin converting enzyme 2 (ACE2) and main protease (MPro) are significant target proteins, mainly involved in the attachment of viral genome to host cells and aid in replication of severe acute respiratory syndrome-coronaviruses or SARS-CoV genome. […] These potential bioactive compounds were considered for molecular docking studies against ACE2 and MPro target proteins to determine the antiviral effects against SARS-COV.
32839612 Here, we evaluate transgenic mice expressing the human angiotensin I-converting enzyme 2 (ACE2) receptor driven by the cytokeratin-18 (K18) gene promoter (K18-hACE2) as a model of SARS-CoV-2 infection. […] Intranasal inoculation of SARS-CoV-2 in K18-hACE2 mice results in high levels of viral infection in lungs, with spread to other organs. […] Thus, the K18-hACE2 model of SARS-CoV-2 infection shares many features of severe COVID-19 infection and can be used to define the basis of lung disease and test immune and antiviral-based countermeasures.
32840378 Herein, to identify potential antiviral agents, 97 natural amide-like compounds known as alkamides and piperamides were tested against SARS-CoV-2 main protease (Mpro) and RNA-dependent RNA polymerase (RdRp), and the human angiotensin-converting enzyme 2 (ACE2) using molecular docking and molecular dynamics simulations.
32840758 The gateway for invasion by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into human host cells is via the angiotensin-converting enzyme 2 (ACE2) transmembrane receptor expressed in multiple immune and nonimmune cell types. […] To further our understanding of the mechanism and pathways of SARS-CoV-2 infection and susceptibility of specific cell- and tissue-types and organ systems to SARS-CoV-2 attack in this communication we analyzed ACE2 expression in 85 human tissues including 21 different brain regions, 7 fetal tissues and 8 controls. […] Besides strong ACE2 expression in respiratory, digestive, renal-excretory and reproductive cells, high ACE2 expression was also found in the amygdala, cerebral cortex and brainstem. […] The highest ACE2 expression level was found in the pons and medulla oblongata in the human brainstem, containing the medullary respiratory centers of the brain, and may in part explain the susceptibility of many CoV-19 patients to severe respiratory distress.
32841215 Mice are refractory to SARS-CoV-2 infection owing to low-affinity binding to the murine angiotensin-converting enzyme 2 (ACE2) protein. […] Here, we evaluated the pathogenesis of SARS-CoV-2 in male and female mice expressing the human ACE2 gene under the control of the keratin 18 promoter (K18). […] In contrast to nontransgenic mice, intranasal exposure of K18-hACE2 animals to 2 different doses of SARS-CoV-2 resulted in acute disease, including weight loss, lung injury, brain infection, and lethality.
32841599 The receptor binding domain (RBD) of the SARS-CoV-2 spike glycoprotein mediates viral attachment to ACE2 receptor and is a major determinant of host range and a dominant target of neutralizing antibodies. […] Here, we experimentally measure how all amino acid mutations to the RBD affect expression of folded protein and its affinity for ACE2. […] Most mutations are deleterious for RBD expression and ACE2 binding, and we identify constrained regions on the RBD’s surface that may be desirable targets for vaccines and antibody-based therapeutics. […] But a substantial number of mutations are well tolerated or even enhance ACE2 binding, including at ACE2 interface residues that vary across SARS-related coronaviruses. […] However, we find no evidence that these ACE2-affinity-enhancing mutations have been selected in current SARS-CoV-2 pandemic isolates.
32841605 The SARS-CoV-2 betacoronavirus uses its highly glycosylated trimeric Spike protein to bind to the cell surface receptor angiotensin converting enzyme 2 (ACE2) glycoprotein and facilitate host cell entry. […] We utilized glycomics-informed glycoproteomics to characterize site-specific microheterogeneity of glycosylation for a recombinant trimer Spike mimetic immunogen and for a soluble version of human ACE2. […] Our results highlight roles for glycans in sterically masking polypeptide epitopes and directly modulating Spike-ACE2 interactions. […] Furthermore, our results illustrate the impact of viral evolution and divergence on Spike glycosylation, as well as the influence of natural variants on ACE2 receptor glycosylation.
32841640 Here we implied the molecular docking and dynamic simulations with emphasis on the unique structural properties of host receptor angiotensin-converting enzyme 2 (ACE2), SARS-CoV2 spike protein and RNA dependent RNA polymerase enzyme (RdRp) of the SARS-CoV2.
32842817 SARS-CoV-2 invades the pulmonary alveolar epithelial cells by binding to the surface receptor, angiotensin-converting enzyme 2 (ACE2). […] Renin-angiotensin system (RAS) modulators can increase levels of ACE2.
32844124 Here, we combined ACE2 coding variants’ analysis in different populations and computational chemistry calculations to probe the effects on SARS-CoV-2/ACE2 interaction. […] ACE2-K26R; which is most frequent in Ashkenazi Jewish population decreased the SARS-CoV-2/ACE2 electrostatic attraction. […] On the contrary, ACE2-I468V, R219C, K341R, D206G, G211R increased the electrostatic attraction; ordered by binding strength from weakest to strongest.
32844126 The ACE2 utilization by the virus leads to local pulmonary inflammation due to ACE2-ATII disbalance.
32844337 Angiotensin-converting enzyme 2 (ACE2), a key counter regulator of the renin-angiotensin system (RAS), is the main entry gate of SARS-CoV-2 into human host cells and an established drug target to prevent heart failure. […] In fact, ACE inhibitors, angiotensin II receptor blockers, and mineralocorticoid antagonists may augment ACE2 levels to protect organs from angiotensin II overload. […] Elevated ACE2 expression on the host cell surface might facilitate viral entrance, at the same time sudden nonadherence to these medications triggers MACEs. […] Although ACE2 generally plays an adaptive role in both healthy subjects and patients with systolic and/or diastolic dysfunction, we conducted a literature appraisal on its maladaptive role. […] Understanding the exact role of ACE2 in COVID-19 patients at risk of heart failure is needed to safely manage RAS inhibitors in frail and non-frail critically ill patients.
32844538 ADAM17 mediates ACE2, IL-6R, and TNF-α shedding. […] ACE2 is the SARS-CoV-2 entry receptor and a key component for the balance of the renin-angiotensin system, inflammation, vascular permeability, and pulmonary homeostasis.
32844987 In this analysis, it is pointed the relationship between the downregulation of angiotensin-converting enzyme 2 (ACE2) and storm cytokines action with the onset of hypercoagulability state, other than the clinical events involved in thrombocytopenia and hyperfibrinolysis progression.
32845122 The first step of SARS-CoV-2 infection is binding of the spike protein’s receptor binding domain to the host cell’s ACE2 receptor on the plasma membrane. […] This probe is capable of engaging in energy transfer quenching with ACE2-conjugated gold nanoparticles to enable monitoring of the binding event in solution. […] Neutralizing antibodies and recombinant human ACE2 blocked quenching, demonstrating a specific binding interaction. […] In cells transfected with ACE2-GFP, we observed immediate binding of the probe on the cell surface followed by endocytosis. […] Neutralizing antibodies and ACE2-Fc fully prevented binding and endocytosis with low nanomolar potency. […] Importantly, we will be able to use this QD nanoparticle probe to identify and validate inhibitors of the SARS-CoV-2 Spike and ACE2 receptor binding in human cells.
32845609 Numerous studies have established beyond doubt that the membrane-bound metalloprotease angiotensin-converting enzyme 2 (ACE2) performs the role of SARS-CoV-2 host-cell receptor. […] Histochemical studies and more recently transcriptomics of mRNA have dissected the cellular localization of the ACE2 enzyme in various tissues, including the central nervous system. […] Epithelial cells lining the nasal mucosae, the upper respiratory tract, and the oral cavity, bronchoalveolar cells type II in the pulmonary parenchyma, and intestinal enterocytes display ACE2 binding sites at their cell surfaces, making these epithelial mucosae the most likely viral entry points. […] Neuronal and glial cells and endothelial cells in the central nervous system also express ACE2.
32846088 A case study is conducted on the structural analysis of the spike proteins of SARS-CoV-2 and SARS-CoV and the human cell receptor ACE2.
32846196 SARS-CoV-2 binds much more strongly than SARS-CoV to the same host receptor, angiotensin-converting enzyme 2 (ACE2).
32847856 Here we first investigated the ability of SARS-CoV-2 and three related coronaviruses to utilize animal orthologs of angiotensin-converting enzyme 2 (ACE2) for cell entry. […] We found that ACE2 orthologs of a wide range of domestic and wild mammals, including camels, cattle, horses, goats, sheep, cats, rabbits and pangolins, were able to support cell entry of SARS-CoV-2, suggesting that these species might be able to harbor and spread this virus. […] In addition, the pangolin and bat coronaviruses, Pangolin-CoV-2020 and Bat-CoV RaTG13, were also found able to utilize human ACE2 and a number of animal-ACE2 orthologs for cell entry, indicating risks of spillover of these viruses into humans in the future. […] We then developed potently anti-coronavirus ACE2-Ig proteins that are broadly effective against the four distinct coronaviruses. […] In particular, through truncating ACE2 at its residue 740 but not 615, introducing a D30E mutation, and adopting an antibody-like tetrameric-ACE2 configuration, we generated an ACE2-Ig variant that neutralizes SARS-CoV-2 at picomolar range. […] These data demonstrate that the improved ACE2-Ig variants developed in this study could potentially be developed to protect from SARS-CoV-2 and some other SARS-like viruses that might spillover into humans in the future.IMPORTANCE The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the currently uncontrolled coronavirus disease 2019 (COVID-19) pandemic. […] In addition, insight into the ability of SARS-CoV-2 and SARS-like viruses to utilize animal orthologs of the SARS-CoV-2 receptor ACE2 might provide structural insight into improving ACE2-based viral entry inhibitors. […] In this study, we found that ACE2 orthologs of a wide range of domestic and wild animals can support cell entry of SARS-CoV-2 and three related coronaviruses, providing insights into identifying animal hosts of these viruses. […] We also developed recombinant ACE2-Ig proteins that are able to potently block these viral infections, providing a promising approach to developing antiviral proteins broadly effective against these distinct coronaviruses.
32848162 A handful of static structures now provide molecular insights into how SARS-CoV-2 and SARS-CoV interact with its host target, which is the angiotensin converting enzyme 2 (ACE2). […] To evaluate this, multiple 500 ns or 1 μs all-atom molecular dynamics simulations were performed to better understand the structural stability and interfacial interactions between the receptor binding domain of the spike (S) protein of SARS-CoV-2 and SARS-CoV bound to ACE2. […] Our results indicate that SARS-CoV-2 and SARS-CoV utilizes unique strategies to achieve stable binding to ACE2. […] Several differences were observed between the residues of SARS-CoV-2 and SARS-CoV that consistently interacted with ACE2. […] Notably, a stable salt bridge between Lys417 of SARS-CoV-2 S protein and Asp30 of ACE2 as well as three stable hydrogen bonds between Tyr449, Gln493 and Gln498 of SARS-CoV-2 and Asp38, Glu35 and Lys353 of ACE2 were observed, which were absent in the ACE2-SARS-CoV interface.
32848446 Large number of angiotensin converting enzyme 2 (ACE2) receptors on cell surfaces, effective innate immune system, and high level of blood lymphocyte have been reported to be the potent reasons for lower incidence of severe symptoms of COVID-19 among children.
32848769 Angiotensin-II converting enzime-2 (ACE2) has been proposed as preferred receptor for SARS-CoV-2 host infection, yet specific proteins participating in the virus entry are not fully known. […] The renin-angiotensin-aldosterone system (RAAS) component ACE2 and DPP4 are proteins dysregulated in diabetes. […] We hypothesize that diabetic patients might be more affected by COVID-19 due to increased presence ACE2 and DPP4 mediating infection and contributing to a compromised vasculature. […] Here, we discuss the role of ACE2 and DPP4 as relevant factors linking the risk of SARS-CoV-2 infection and severity of COVID-19 in diabetic patients and present an outlook on therapeutic potential of current drugs targeted against RAAS and DPP4 to treat or prevent COVID-19-derived vascular complications.
32848776 In this proposed pathway, membrane fusion and cytoplasmic entry of SARS-CoV-2 virus via ACE2 and TMPRSS2-expressing respiratory epithelial cells, including pulmonary type-II pneumocytes, provoke an initial immune response featuring inflammatory cytokine production coupled with a weak interferon response, particularly in IFN-λ-dependent epithelial defense.
32849309 We hypothesize here that increased ACE2 expression in adipose tissue displayed by people with obesity may increase SARS-CoV-2 infection and accessibility to this tissue.
32849415 SARS-CoV entry receptor ACE2 sequence of P. medius was 82.7% identical with ACE2 of Rhinolophus sinicus bats, thought to be the natural host of SARS-CoV.
32849666 SARS-CoV-2 binds to ACE2 for cell entry, downregulating it: an impaired DABK inactivation could lead to an enhanced activity of B1-receptors, and the accumulation of Ang II, through a negative feedback loop, may result in decreased ACE activity, with consequent increase of BK.
32849833 These include some ongoing mutations that can alter the virulence of the circulating SARS-CoV-2 strains, host factors like innate immunity, genetic diversity in immune responses, epigenetic factors, genetic polymorphisms of ACE2 receptors, micro RNAs and universal BCG vaccination, and environmental factors like high temperature and humidity which may alter the viability and transmissibility of the strain.
32850499 The spike protein (S) of this virus enables binding to the human receptor ACE2, and hence presents a prime target for vaccines preventing viral entry into host cells.
32850607 Furthermore, in-vivo studies of the angiotensin-converting enzyme 2 (ACE2) showed higher expression in the kidneys of male than female patients, which may explain the differences in susceptibility and progression of COVID-19 between male and female patients. […] However, it remains unknown whether the expression of ACE2 differs in the lungs of male or female patients.
32850927 The discovery that the SARS-CoV-2 uses the renin-angiotensin system (RAS) component ACE2 as a receptor to invade host epithelial cells and cause organs damage resulted in a debate regarding the role of ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) therapies during COVID-19 pandemic.
32850973 We propose that a cooperating therapy using inhibitors against multiple targets altogether i.e., ACE2, integrins and sugars could be definitely more effective.
32850977 It is believed that interaction between angiotensin converting enzyme 2 (ACE2) cell receptor and viral Spike protein mediates the coronavirus entry into human respiratory epithelial cells and establishes the host tropism. […] ACE2 receptor is highly expressed in airway epithelial cells.
32850978 Here we report our perspective on applying GapmeR technology in combination with recombinant angiotensin-converting enzyme 2 (ACE2) in the treatment of COVID-19 patients. […] The recombinant ACE2 protein, the efficacy of which is being evaluated in clinical trials, will bind to the spike (S) glycoprotein of extracellular SARS-CoV-2 and potentially block viral infectivity. […] We propose that combining inhalable SARS-CoV-2-targeted GapmeRs with recombinant ACE2 could provide a viable and rapidly implementable more effective therapeutic approach for eradicating SARS-CoV-2 and save millions of lives.
32850989 The cardiovascular damage may be related to the imbalance of the renin-angiotensin-system (RAS) as this virus binds the Angiotensin-Converting-Enzyme 2 (ACE2), expressed on the lung alveolar epithelial cells, to enter into cells. […] Virus internalization may cause a downregulation of ACE2 on host cell surface that could lead to a local increased level of angiotensin II (AII) and a reduced level of angiotensin 1-7 (A1-7). […] Pharmacological strategies that interfere with the viral attachment to ACE2 (umifenovir and hydroxychloroquine/chloroquine) or that modulate the RAS (analogous of A1-7 and ACE2, losartan) are in clinical development for COVID-19. […] The use of RAS inhibitors has also become a matter of public concern as these drugs may increase the mRNA expression and levels of ACE2 and impact the virulence and transmission of SARS-COV-2. […] Data on the effect of RAS inhibitors on ACE2 mRNA expression are scarce.
32851183 Furthermore, loss of Miz1 up-regulates the expression of Ace2, the receptor for SARS-CoV-2.
32851697 Via bioinformatic analysis, we identified the existence of ACE2 and TMPRSS2 expression in human TE as well as in the first- and second- trimester placentas. […] In human TE data, 54.4% of TE1 cells, 9.0% of CTBs, 3.2% of EVTs and 29.5% of STBs were ACE2 positive. […] Amongst the placental cells, 20.4% of CTBs, 44.1% of STBs, 3.4% of EVT_8W and 63% of EVT_24W were ACE2 positive. […] Pathway analysis revealed associations to morphogenesis of branching structure, extracellular matrix interaction, oxygen binding and antioxidant activity in ACE2+TMPRSS2+ EVT_24W cells. […] The ACE2+TMPRSS2+ TE1 cells were correlated with an increased capacity of viral invasion, epithelial cell proliferation and cell adhesion. […] Based on immunohistochemical results, expression level of ACE2 and TMPRSS2 in first- and second- and third-trimester placentas was observed. […] Our study has demonstrated the presence of ACE2 and TMPRSS2 positive cells in the human TE and placentas at different stages of pregnancy, which indicates the possibility that the SARS-CoV-2 could spread via the placenta and cause intrauterine fetal infection.
32851855 ACE2 is a homolog of the ACE that acts on several substrates in the renin-Ang (angiotensin) system. […] With unprecedented speed, scientific research has solved the structure of SARS-CoV-2 and imaged its binding with the ACE2 receptor. […] In SARS-CoV-2 infection, the viral S (spike) protein receptor-binding domain binds to ACE2 to enter the host cell. […] ACE2 expression in the lungs is relatively low, but it is present in type II pneumocytes-a cell type also endowed with TMPRSS2 (transmembrane protease serine 2). […] This protease is critical for priming the SARS-CoV-2 S protein to complex with ACE2 and enter the cells. […] Herein, we review the current understanding of the interaction of SARS-CoV-2 with ACE2 as it has rapidly unfolded over the last months. […] While it should not be assumed that we have a complete picture of SARS-CoV-2 mechanism of infection and its interaction with ACE2, much has been learned with clear therapeutic implications. […] Potential therapies aimed at intercepting SARS-CoV-2 from reaching the full-length membrane-bound ACE2 receptor using soluble ACE2 protein and other potential approaches are briefly discussed as well.
32852624 Angiotensin-converting enzyme 2 (ACE2), a specific high-affinity angiotensin II-hydrolytic enzyme, is the vector that facilitates cellular entry of SARS-CoV-1 and the novel SARS-CoV-2 coronavirus. […] It has been postulated that potential functional modulation of ACE2 by estrogen may explain the sex difference in morbidity and mortality. […] We review here the evidence regarding the role of estrogenic hormones in ACE2 expression and regulation, with the intent of bringing to the forefront potential mechanisms that may explain sex differences in SARS-CoV-2 infection and COVID-19 outcomes, assist in management of COVID-19, and uncover new therapeutic strategies.
32853823 Entry of the SARS-CoV-2 into the host cell involves interaction of the virus (via the receptor-binding domain (RBD) of its spike glycoprotein) with the membrane-bound form of angiotensin-converting enzyme 2 (ACE2) followed by the virus-ACE2 complex internalization by the cell. […] Since ACE2 is expressed in various tissues, such as brain, gut, heart, kidney, and lung, and since these organs represent obvious targets for the SARS-CoV-2 infection, therapeutic approaches were developed to either inhibit ACE2 or reduce its expression as a means of prevention of the virus entry into the corresponding host cells. […] The problem here is that in addition to be a receptor for the SARS-CoV-2 entry into the host cells, ACE2 acts as a key component of the renin-angiotensin-aldosterone system (RAAS) aimed at the generation of a cascade of vasoactive peptides coordinating several physiological processes. […] In RAAS, ACE2 degrades angiotensin II, which is a multifunctional CVD-promoting peptide hormone and converts it to a heptapeptide angiotensin-(1-7) acting as the angiotensin II antagonist.
32854108 SARS-CoV-2 cannot infect wild-type laboratory mice owing to inefficient interactions between the viral spike protein and the mouse orthologue of the human receptor, angiotensin-converting enzyme 2 (ACE2)4. […] Here we used reverse genetics5 to remodel the interaction between SARS-CoV-2 spike protein and mouse ACE2 and designed mouse-adapted SARS-CoV-2 (SARS-CoV-2 MA), a recombinant virus that can use mouse ACE2 for entry into cells. […] SARS-CoV-2 MA caused more severe disease in aged mice, and exhibited more clinically relevant phenotypes than those seen in Hfh4-ACE2 transgenic mice, which express human ACE2 under the control of the Hfh4 (also known as Foxj1) promoter. […] We demonstrate the utility of this model using vaccine-challenge studies in immune-competent mice with native expression of mouse ACE2.
32855181 The first assay is surface plasmon resonance (SPR) based and can quantitate both antibody binding to the SARS-CoV-2 spike protein and blocking to the Angiotensin-converting enzyme 2 (ACE2) receptor in a single experiment. […] The second assay is enzyme-linked immunosorbent assay (ELISA) based and can measure competition and blocking of the ACE2 receptor to the SARS-CoV-2 spike protein with antispike antibodies.
32855401 A subset of the antibodies exert their inhibitory activity by abrogating binding of the RBD to the human ACE2 receptor.
32857620 TMPRSS2, ACE2 and TMPRSS11D are genes coding for proteins necessary for SARS-CoV-2 activation, infection and transmission.
32858233 Here we investigated whether genetic variation in the key genes for viral entry to host cells-ACE2 and TMPRSS2-and sensing of viral genomic RNAs (i.e., TLR3/7/8) could explain the variation in incidence across diverse ethnic groups. […] Genetic determinant for the binding affinity between SARS-CoV-2 and ACE2 does not show significant difference between populations. […] Nonetheless, a systematic mutagenesis study on the receptor binding domain of ACE2 is required to understand the difference in host-viral interaction across populations.
32858292 SARS-CoV-2 is reported to have a high affinity for the angiotensin-converting enzyme 2 (ACE2) receptor. […] Indirectly, exposure to PM increases ACE2 expression in the lungs which facilitates SARS-CoV-2 viral adhesion. […] Thus, the high risk of SARS-CoV-2 in heavily polluted regions can be explained by upregulation of ACE2 caused by PM.
32861070 Angiotensin converting enzyme 2 (ACE2) has been proven to be a major receptor for SARS-CoV-2 and could mediate virus entry into cells. […] The mRNA expressions of both ACE2 and TMPRSS2 were observed in the heart, digestive tract, liver, kidney, brain and other organs. […] SARS-CoV-2 may have a capacity to infect extrapulmonary organs due to the expressions of ACE2 and TMPRSS2 in the cells and tissues of these organs. […] It seems that there is a potential involvement of ACE2 and TMPRSS2 expressions in the virus infection of extrapulmonary organs and the manifestation of symptoms related to these organs in patients with COVID-19. […] Here, we revealed the expressions of ACE2 and TMPRSS2 in extrapulmonary organs, and we also summarized the clinical manifestation and the management of extrapulmonary complications in patients with COVID-19.
32861340 Angiotensin-converting enzyme-2 (ACE2) is necessary to facilitate SARS-CoV-2 infection, but-owing to its essential metabolic roles-it may be difficult to target it in therapies. […] Transmembrane protease serine 2 (TMPRSS2), which interacts with ACE2, may be a better candidate for targeted therapies. […] Using publicly available expression data, we show that both ACE2 and TMPRSS2 are expressed in many host tissues, including lung. […] The highest expression of ACE2 is found in the testes, whereas the prostate displays the highest expression of TMPRSS2. […] Given the increased severity of disease among older men with SARS-CoV-2 infection, we address the potential roles of ACE2 and TMPRSS2 in their contribution to the sex differences in severity of disease. […] We show that expression levels of ACE2 and TMPRSS2 are overall comparable between men and women in multiple tissues, suggesting that differences in the expression levels of TMPRSS2 and ACE2 in the lung and other non-sex-specific tissues may not explain the gender disparities in severity of SARS CoV-2.
32862058 Using comparative immunofluorescence, we examined the localization and relative tissue abundance of SARS-CoV2 spike glycoprotein (CoV2 SP) along with the co-localization of two SARS-CoV2 viral entry proteins angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). […] We further identified the predominance of ACE2 expression in comparison with TMPRSS2. […] Importantly, both CoV2 SP and ACE2 expression consistently localized primarily within the outer syncytiotrophoblast layer placental villi, a key physiologic interface between mother and fetus.
32863223 SARS-CoV-2 infects human cells by binding to the cellular surface protein angiotensin-converting enzyme 2 (ACE2); in addition, the cellular transmembrane serine protease 2 (TMPRSS2) is needed for priming of the spike (S) protein of the virus. […] Herein, we performed an expression profiling meta-analysis of ACE2, TMPRSS2 and CTSB/L genes (and proteins) in public repository databases and found that all are widely expressed in human tissues; also, the ACE2 and TMPRSS2 genes tend to be co-regulated. […] The ACE2 and TMPRSS genes expression is (among others) suppressed by TNF, and is induced by pro-inflammatory conditions including obesity, Barrett’s esophagus, stomach infection by helicobacter pylori, diabetes, autoimmune diseases and oxidized LDL; by exercise, as well as by growth factors, viruses’ infections, cigarette smoke, interferons and androgens. […] Regarding currently investigated therapies interferon-beta induced ACE2 gene expression in bronchial epithelial cells, while chloroquine tends to upregulate CTSB/L genes. […] Finally, we analyzed KEGG pathways modulated by ACE2, TMPRSS2 and CTSB/L and probed DrugBank for drugs that target modules of the affected pathways.
32864299 Its mechanism of action (MOA) includes the interference in the endocytic pathway, blockade of sialic acid receptors, restriction of pH mediated spike (S) protein cleavage at the angiotensin-converting enzyme 2 (ACE2) binding site and prevention of cytokine storm.
32864572 SARS-CoV-2 like SARS-CoV binds with angiotensin-converting enzyme 2 (ACE2) present on human cells. […] SARS-CoV has been found to downregulate ACE2 and SARS- CoV-2 infection has been found to be associated with increased level of Angiotensin II. […] Based on these facts, we presume that SARS-CoV-2 like SARS-CoV downregulates ACE2, and in absence/reduced activity of ACE2, level of angiotensin (1-7) and angiotensin (1-9) is decreased while that of angiotensin II is increased and increased level of angiotensin II has been found to correlate with lung injury and viral load. […] We presume that restoration of normal functioning of renin-angiotensin system with recombinant human angiotensin-converting enzyme 2 (rhACE2), angiotensin (1-7) and angiotensin (1-9) may be an effective therapeutic measure but studies will be required to test this hypothesis and explore its possible role in treatment of COVID-19.
32864934 The SARS-CoV2 enters human cells through the spike protein binding to angiotensin-converting enzyme 2 (ACE2), which is important to cardiovascular modulation and endothelial signaling. […] As ACE2 is highly expressed in lung tissue, patients have been progressing to acute respiratory injury at an alarming frequency during the Coronavirus Disease (COVID-19) pandemic.
32864982 In this review, we seek evidence showing the role of coronavirus spike protein (S-protein) and its potential cellular receptor, angiotensin-converting enzyme 2 (ACE2), during infection of coronaviruses, including the newly SARS-CoV-2 and its similar strain SARS-CoV. […] This review also discusses the therapeutic effect of inhibiting the renin-angiotensin system cascade, a target of ACE2, in patients having coronavirus with cardiovascular disease.
32865603 SARS-CoV‑2 uses ACE2 a receptor to enter host cells.
32866534 Angiotensin-converting enzyme 2 (ACE2) receptor serves as an entry point for this deadly virus while the proteases like furin, transmembrane protease serine 2 (TMPRSS2) and 3 chymotrypsin-like protease (3CLpro) are involved in the further processing and replication of SARS-CoV-2. […] The interaction of SP with ACE2 and these proteases results in the SARS-CoV-2 invasion and fast epidemic spread. […] The small molecular inhibitors are reported to limit the interaction of SP with ACE2 and other proteases. […] The representative compounds A_BR4, A_BR9, A_BR18, A_BR22 and A_BR28 restricted the interaction of SARS-CoV-2 SP with ACE2 and host proteases furin and TMPRSS2.
32866780 The receptor binding domain (RBD) of spike protein S1 domain SARS-CoV-2 plays a key role in the interaction with ACE2, which leads to subsequent S2 domain mediated membrane fusion and incorporation of viral RNA into host cells. […] In this study we tend to repurpose already approved drugs as inhibitors of the interaction between S1-RBD and the ACE2 receptor. 2456 approved drugs were screened against the RBD of S1 protein of SARS-CoV-2 (target PDB ID: 6M17). […] As the interacting surface between S1-RBD and ACE2 comprises of bigger region, the interacting surface was divided into 3 sites on the basis of interactions (site 1, 2 and 3) and a total of 5 grids were generated (site 1, site 2, site 3, site 1+site 2 and site 2+site 3). […] On the basis of molecular dynamics studies, we come up with 10 molecules with favourable interaction profile, which also interacted with physiologically important residues (residues taking part in the interaction between S1-RBD and ACE2. […] However, while considering the relative side chain fluctuations when compared to the S1-RBD: ACE2 complex riboflavin, fenoterol, cangrelor and vidarabine emerged out as molecules with prolonged relative stability. […] We identified 4 already approved drugs (riboflavin, fenoterol, cangrelor and vidarabine) as possible agents for repurposing as inhibitors of S1:ACE2 interaction. […] In-vitro validation of these findings are necessary for identification of a safe and effective inhibitor of S1: ACE2 mediated entry of SARS-CoV-2 into the host cell.
32867305 It is known that ACE2 acts as a receptor for this pathogen, but the viral entry into the target cell also depends on other proteins.
32867666 RNA-dependent RNA polymerase (b.) serine protease and (c.) proteolytic activation pathways or the cell membrane receptor called the angiotensin converting enzyme-2 (ACE2).
32870351 Due to the different structural properties of GPCR, IFNAR2, ACE2 and Spike of 2019-nCoV, their ligands will either bind the extracellular domain of IFNAR2/ACE2/Spike or the specific loops of the GPCR on the envelope of the recombinant herpes virions to induce dynamic charge distribution changes that lead to the variable electron transition for detection.
32870820 Here, we present a safe and efficient protein-based assay for the detection of serum and plasma antibodies that block the interaction of the SARS-CoV-2 spike protein receptor binding domain (RBD) with its receptor, angiotensin-converting enzyme 2 (ACE2).
32871306 We discuss about how the virus-induced downregulation of the angiotensin converting enzyme-2 (ACE2) receptor, used to enter the host cell, could affect the renin-angiotensin system, attempting to clarify the doubts about the use of ACE inhibitors and Angiotensin-II receptor blockers in COVID-19 patients.
32871846 We carried out a docking study to determine if ivermectin might be able to attach to the SARS-CoV-2 spike receptor-binding domain bound with ACE2. […] Ivermectin docked in the region of leucine 91 of the spike and histidine 378 of the ACE2 receptor. […] The binding energy of ivermectin to the spike-ACE2 complex was -18 kcal/mol and binding constant was 5.8 e-08.
32872802 The coronavirus 2019 (COVID-19) respiratory disease is caused by the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), which uses the enzyme ACE2 to enter human cells. […] This disease is characterized by important damage at a multi-organ level, partially due to the abundant expression of ACE2 in practically all human tissues. […] However, not every organ in which ACE2 is abundant is affected by SARS-CoV-2, which suggests the existence of other multi-organ routes for transmitting the perturbations produced by the virus.
32873192 We posit that nanoparticles decorated with ACE2, the receptor for SARS-CoV-2, could be exploited as decoys to intercept the virus before it infects cells in the respiratory tract.
32873611 Baseline levels of CD8+ T cells, resting NK cells, and activated NK cells, as well as cytokines that recruit these cells, are significantly lower in lung tissues with high expression of the SARS-CoV-2 entry receptor angiotensin-converting enzyme 2 (ACE2). […] Importantly, ACE2 mRNA and protein levels very strongly correlate in human cells and tissues. […] Elevated ACE2 expression increases sensitivity to coronavirus infection. […] Thus, the results suggest that some individuals may be exceedingly susceptible to develop severe COVID-19 due to concomitant high preexisting ACE2 and TMPRSS expression and low baseline cytotoxic lymphocyte levels in the lung.IMPORTANCE COVID-19 is caused by the highly contagious coronavirus SARS-CoV-2 and currently has detrimental human health, community, and economic impacts around the world. […] The ACE2 gene encodes the receptor on human cells that the virus uses to infect these cells. […] This study finds that if the lungs of healthy individuals have high levels of ACE2, they typically have low levels of the immune cells that eliminate viruses.
32873700 Both SARS-CoV and SARS-CoV-2 (COVID-19) use angiotensin-converting enzyme 2 (ACE2) and TMPRSS2 to facilitate entry to cells, but with SARS-CoV-2 human-to-human transmission is much higher than SARS-CoV.
32875490 While the potential for benefit with the use of renin-angiotensin-aldosterone system inhibitors (RAASi) and the risks from stopping them is more evident, potential harm by RAΑSi may also be caused by the increase in the activity of the ACE2 receptor, the inefficient counter regulatory axis in the lungs in which the proinflammatory prolyloligopeptidase (POP) is the main enzyme responsible for the conversion of deleterious angiotensin (ANG) II to protective ANG [1-7] and the proinflammatory properties of ACE2(+) cells infected with SARS-CoV-2.
32875598 A low proportion of lymphocytes may express the main receptor for SARS-CoV-2, called angiotensin-converting enzyme 2 (ACE2). […] Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can also use ACE2-independent pathways to enter lymphocytes.
32876296 The expression of ACE2 receptors in the vascular endothelium may explain the histological changes of placentas from pregnant women infected by SARS-CoV-2.
32876900 The etiological agent of COVID-19 is SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), an RNA virus with a glycoprotein-studded viral envelope that uses ACE2 (angiotensin-converting enzyme 2) as a functional receptor for infecting the host cells. […] Thus, the interaction of the envelope spike proteins with ACE2 on host cells determines the tropism and virulence of SARS-CoV-2.
32878480 These three factors increase the expression of angiotensin I converting enzyme 2 (ACE2), a key receptor involved in the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-the etiological agent of COVID-19-into respiratory tract epithelial cells. […] To date, no study has examined whether an increased fraction of inspired oxygen (FiO2) may affect the expression of SARS-CoV-2 entry receptors and co-receptors, including ACE2 and the transmembrane serine proteases TMPRSS1, TMPRSS2, and TMPRSS11D. […] While gene expression of ACE2 was unaffected, gene and protein expression of TMPRSS11D was consistently upregulated by exposure to an elevated FiO2.
32878881 The infectivity, pathogenesis and infection of this virus are dependent on the interaction of SARS-CoV2 spike protein with human angiotensin converting enzyme 2 (hACE2). […] In the present study, we are reporting a de novo designed novel hybrid antiviral ‘VTAR-01’ molecule that binds at the interface of RBD-hACE2 interaction. […] A series of antiviral molecules were tested for binding at the interface of RBD-hACE2 interaction. […] In silico screening, molecular mechanics and molecular dynamics simulation (MDS) analysis suggest ribavirin, ascorbate, lopinavir and hydroxychloroquine have strong interaction at the RBD-hACE2 interface. […] Retrosynthetic analysis and combinatorial synthesis, along with docking and MDS, identified that VTAR-01 interacts with the interface of the RBD-ACE2 complex. […] MDS analysis confirmed its interaction with the RBD-ACE2 interface by involving Glu35 and Lys353 of ACE2, as well as Gln493 and Ser494 of RBD. […] Interaction of spike protein with ACE2 is essential for pathogenesis and infection of this virus; hence, this in silico designed hybrid antiviral molecule (VTAR-01) that binds at the interface of RBD-hACE2 may be further developed to control the infection of SARS-CoV2.
32879112 Angiotensin-converting enzyme 2 (ACE2), previously known as a cell receptor of severe acute respiratory syndrome coronavirus (SARS-CoV), is putatively responsible for mediating COVID-19. […] In this review, we detail our current understanding of the interaction between S protein and ACE2 in the process of virus infection and the potential pathogenesis of SARS-CoV-2, which has critical implications for exploring the potential therapeutic strategies for COVID-19.
32881059 The secretion of a spike protein portion will function as a competitive antagonist by interfering with the binding of coronavirus to the angiotensin-converting enzyme 2 (ACE2) receptor. […] The secreted protein binding to the ACE2 receptor provides a unique mechanism of action for treatment to all strains of coronavirus in naïve patients, by blocking the ACE2 receptor site.
32881661 We had perform molecular docking studies on three different proteins of novel corona virus namely COVID-19 main protease (3CL pro), papain-like protease (PL pro) and spike protein (S) attached to ACE2 binding domain.
32882331 First, ACE2 is the cellular receptor for SARS-CoV-2, and expression of the ACE2 gene could regulate the individuaĺs susceptibility to infection. […] In addition, the balance between ACE1 and ACE2 activity has been implicated in the pathogenesis of respiratory diseases and could play a role in the severity of COVID-19. […] Functional ACE1/ACE2 gene polymorphisms have been associated with the risk of cardiovascular and pulmonary diseases, and could thus also contribute to the outcome of COVID-19. […] The ACE1 insertion/deletion and ACE2 rs2285666 polymorphism were determined. […] We also sequenced the ACE2 coding nucleotides in a group of patients. […] The ACE2 polymorphism was not associated with the disease outcome. […] The ACE2 sequencing showed no coding sequence variants that could explain an increased risk of developing COVID-19.
32882868 One of the potential therapeutic targets of anti-COVID-19 drugs is the angiotensin-converting enzyme 2 (ACE2). […] ACE2 was identified as a key functional receptor for CoV associated with COVID-19. […] ACE2, which is located on the surface of the host cells, binds effectively to the spike protein of CoV, thus enabling the virus to infect the epithelial cells of the host. […] Thus, it is being postulated that these flavonoids might also interact with ACE2. […] This article summarizes the natural flavonoids with potential efficacy against COVID-19 through ACE2 receptor inhibition.
32883010 The ocular surface and retina have the necessary proteins, Transmembrane Serine Protease 2 (TMPRSS2), CD147, Angiotensin-Converting Enzyme 2 (ACE2) and Cathepsin L (CTSL) necessary to be infected with SARS-CoV-2.
32883368 Angiotensin converting enzyme 2 (ACE2), being the main cell receptor of SARS-CoV-2, plays a role in the entry of the virus into the cell. […] We found 825 differentially expressed genes correlated with ACE2.
32883878 First, ACE2, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor, is reduced in the respiratory tract in children.
32885037 Currently, there is no clear evidence for human neuronal or astrocyte expression of angiotensin-converting enzyme 2 (ACE2), the major receptor for viral entry, but ACE2 expression may be activated by inflammation, and a comparison of healthy and infected brains is important.
32885345 KEY POINTS: • Inflammatory cytokines play an essential role in the pathogenesis of COVID-19 • ACE2 dysfunctions are related to the with COVID-19 and autoimmune diseases • The use autoimmune diseases drugs can be useful in treating COVID-19.
32886331 In SARS-CoV-2 infection, intrinsically disordered regions are observed at the interface of the spike protein and ACE2 receptor, providing a shape complementarity to the complex. […] The key residues of the spike protein have stronger binding affinity with ACE2. […] The overall history and mechanism of entry of SARS-CoV-2 along with structural study of spike-ACE2 complex provide insights to understand disease pathogenesis and development of vaccines and drugs.
32887634 Using platelets from healthy volunteers, non-COVID-19 and COVID-19 patients, as well as wild-type and hACE2 transgenic mice, we evaluated the changes in platelet and coagulation parameters in COVID-19 patients. […] We investigated ACE2 expression and direct effect of SARS-CoV-2 virus on platelets by RT-PCR, flow cytometry, Western blot, immunofluorescence, and platelet functional studies in vitro, FeCl3-induced thrombus formation in vivo, and thrombus formation under flow conditions ex vivo. […] Platelets expressed ACE2, a host cell receptor for SARS-CoV-2, and TMPRSS2, a serine protease for Spike protein priming. […] SARS-CoV-2 and its Spike protein directly enhanced platelet activation such as platelet aggregation, PAC-1 binding, CD62P expression, α granule secretion, dense granule release, platelet spreading, and clot retraction in vitro, and thereby Spike protein enhanced thrombosis formation in wild-type mice transfused with hACE2 transgenic platelets, but this was not observed in animals transfused with wild-type platelets in vivo. […] Further, we provided evidence suggesting that the MAPK pathway, downstream of ACE2, mediates the potentiating role of SARS-CoV-2 on platelet activation, and that platelet ACE2 expression decreases following SARS-COV-2 stimulation. […] Recombinant human ACE2 protein and anti-Spike monoclonal antibody could inhibit SARS-CoV-2 Spike protein-induced platelet activation. […] Our findings uncovered a novel function of SARS-CoV-2 on platelet activation via binding of Spike to ACE2.
32887876 SARS-CoV-2 enters host cells through an interaction between the spike glycoprotein and the angiotensin converting enzyme 2 (ACE2) receptor. […] Here, we report the isolation and characterization of an alpaca-derived single domain antibody fragment, Ty1, that specifically targets the receptor binding domain (RBD) of the SARS-CoV-2 spike, directly preventing ACE2 engagement. […] Ty1 binds the RBD with high affinity, occluding ACE2. […] A cryo-electron microscopy structure of the bound complex at 2.9 Å resolution reveals that Ty1 binds to an epitope on the RBD accessible in both the ‘up’ and ‘down’ conformations, sterically hindering RBD-ACE2 binding.
32888287 SARS-CoV and SARS-CoV-2 use angiotensin-converting enzyme 2 (ACE2) as target receptor, so ACE2 plays a central role for viral transmission and initial organ involvement.
32888876 There is growing evidence that angiotensin-converting enzyme 2 (ACE2), the main host cell receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is highly expressed on the epithelial cells of the tongue and of the salivary glands, which may explain the development of dysgeusia in patients with COVID-19. […] A short review of the literature regarding the important role of ACE2 in SARS-CoV-2 cellular entry is also provided, bringing new insights into oral keratinocytes and minor salivary glands as potential targets.
32889701 These drugs either act through virus-related targets such as RNA genome, polypeptide packing and uptake pathways or target host-related pathways involving angiotensin-converting enzyme-2 (ACE2) receptors and inflammatory pathways.
32890967 SARS-CoV-2 entry into host cells is characterized by viral spike protein interaction with cellular angiotensin-converting enzyme 2 (ACE2) and serine protease TMPRSS2. […] Propolis components have inhibitory effects on the ACE2, TMPRSS2 and PAK1 signaling pathways; in addition, antiviral activity has been proven in vitro and in vivo.
32891630 SARS-CoV-2 utilizes the IMPα/β1 heterodimer to enter host cell nuclei after gaining cellular access through the ACE2 receptor.
32891636 Angiotensin-converting enzyme 2 (ACE2) is a COVID-19 entry receptor regulating host cell infection. […] A recent study reported that ACE2 is expressed in cardiomyocytes. […] In this study, we aimed to explore if there are microRNA (miRNA) molecules which target ACE2 and which may be exploited to regulate the SARS-CoV-2 receptor. […] Our data reveal that both Ace2 mRNA and Ace2 protein levels are inhibited by miR-200c in rat primary cardiomyocytes and importantly, in human iPSC-derived cardiomyocytes. […] We report the first miRNA candidate that can target ACE2 in cardiomyocytes and thus may be exploited as a preventive strategy to treat cardiovascular complications of COVID-19.
32892687 Activation of several proteases facilitates the interaction of viral spike proteins (S1) and ACE2 receptor. […] This leads to cleavage of host ACE2 receptors. […] ACE2 activity counterbalances the angiotensin II effect, its loss may lead to elevated angiotensin II levels with modulation of platelet function, size and activity.
32893646 The 2019 coronavirus is different from SARS-CoV, but it has the same host receptor: human angiotensin-converting enzyme 2 (ACE2).
32894568 The corresponding three genomic phases include the “ACE2, ANPEP transcripts in the initial phase”, “EGFR and IGF2R transcripts in the propagating phase” and the “immune system related critical gene involvements of the complicating phase”. […] Regarding the specific disease treatments, MAS agonists, TXA127, Angiotensin (1-7) and soluble ACE2 could have therapeutic potential for the COVID-19 course.
32897211 These ingredients activate renin-angiotensin system signaling pathway and apoptosis signaling pathway by regulating 10 protein targets (ACE, ACE2, AGTR1, FURIN, TNF, CASP3, CASP6, DPP4, MCL1 and POLD1) to execute 42 biological functions such as renin-angiotensin regulation of blood volume and systemic arterial blood pressure to treat COVID-19.
32898168 Expression of interferon-responsive genes, including ACE2, increased as a function of viral load, while transcripts for B cell-specific proteins and neutrophil chemokines were elevated in patients with lower viral load.
32899010 The virus can directly or indirectly damage the pancreatic islets and cause stress hyperglycemia by causing cytokine storms, acute inflammatory reactions, binding to the ACE2 receptor, etc.
32899439 Accordingly, we recently published a genetic hypothesis on the role of RAS-pathway genes (ACE1, rs4646994, rs1799752, rs4340, rs13447447; and ACE2, rs2285666, rs1978124, rs714205) and ABO-locus (rs495828, rs8176746) in COVID-19 prognosis, suspecting inherited genetic predispositions to be predictive of COVID-19 severity. […] Finally, ACE1 and ACE2 haplotypes seem to provide plausible explanations for why SARS-CoV-2 have affected more heavily some ethnic groups, namely people with European ancestry, than Asians.
32899833 In particular, treatments with angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-receptor blockers (ARB) may help to reduce hyperinflammation and viral propagation, while infusion of soluble ACE2 may trap plasma viral particles and increase cardioprotective Ang-(1-9) and Ang-(1-7) peptides. […] The association of specific ACE2 polymorphisms with increased susceptibility of infection and related CV pathologies suggests potential genetic therapies.
32900752 It has also been found that the ACE2 receptor of SARS-CoV-2 is expressed more in the pancreas than the lungs.
32901762 This narrative review summarizes the main aspects underlying the new coronavirus SARS-CoV-2, its epidemiology, pathophysiology, pointing to differences of SARS-CoV-2 main receptors ACE2, in terms of expression and the amount of soluble ACE2 in the circulation of children, men and women, and also in those with risk factors such as the smokers and pregnant women or presenting with comorbidities (diabetes, obesity, hypertension and other cardiovascular diseases, renal and CNS pre-existing diseases).
32901940 Angiotensin-converting enzyme 2 (ACE2) is the gateway to SARS-CoV and SARS-CoV-2, so our knowledge of SARS-CoV-2 can help us to complete its mechanism of interaction with ACE2 and virus endocytosis, which can be interrupted by neutralizing small molecules or proteins. […] ACE2 also plays a crucial role in lung injury.
32902005 There are many possible mechanisms through which GZ acts against viruses: increasing nitrous oxide production in macrophages, affecting transcription factors and cellular signalling pathways, directly altering the viral lipid-bilayer membrane, and binding to the ACE2 receptor. […] The most recently published papers on the distribution of ACE2 in the human body and documented binding of GZ to this receptor, as well as its antiviral activity, suggest that GZ can be used as a therapeutic for COVID-19 and as a preventive agent against SARS-CoV-2.
32902372 Through computational analyses, we have identified homologous genomic regions within the ORF1ab and S genes that could facilitate recombination, and have analysed co-expression patterns of the cellular receptors for SARS-CoV-2 and MERS-CoV, ACE2 and DPP4, respectively, to identify human anatomical sites that could facilitate co-infection.
32902940 Angiotensin-converting enzyme 2 (ACE2) has transient overexpression and increased activity during pregnancy, which is now confirmed as the receptor of SARS-CoV-2 and plays essential roles in human infection and transmission.
32903227 Angiotensin-converting enzyme 2 (ACE2) protein, which has been proven to be a cell receptor for SARS-CoV-2, is expressed in the glandular cells of gastric, duodenal, and rectal epithelia, supporting the entry of SARS-CoV-2 into the host cells.
32903321 The new coronavirus (SARS-CoV-2), which has been responsible for the recent coronavirus disease 2019 (COVID-19) pandemic, uses the cell receptor angiotensin converting enzyme-2 (ACE2) for entry and the serine protease TMPRSS2 for spike (S) protein priming. […] Meanwhile, the presence of B0AT1 (SLC6A19) may prevent TMPRSS2 from accessing the cutting position on ACE2. […] The single-cell transcription datasets of the human cell landscape (HCL) and other relevant single-cell transcription databases were used to analyze the expression of ACE2, TMPRSS2, and SLC6A19 in various organs and tissues, but mainly in the kidney. […] ACE2 was significantly expressed in the S1, S2, and S3 segments of proximal tubule (PT) cells. […] Unexpectedly, although expressed on various renal tubule populations, SLC6A19 was mainly enriched in PT cells, in line with ACE2 expression. […] Although alveolar-type (AT) 2 cells of the lung and intestinal epithelial cells expressed ACE2 as well as PT cells, AT 2 cells significantly expressed TMPRSS2 but not SLC6A19, while all 3 genes were significantly expressed in intestinal epithelial cells. […] ACE2 was widely expressed in specific cell subgroups of various human tissues, especially in intestinal epithelial cells, kidney PT cells, and also AT 2 cells of the lung.
32903561 Angiotensin-converting enzyme 2 (ACE2) has been identified as the functional receptor for Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2). […] The aim of the present study was to investigate the expression of ACE2 in the gastrointestinal tract of domestic (cat) and wild (tiger) felines. […] The tissues were processed for immunofluorescence assay with an anti-human ACE2 antibody. […] In both the species, ACE2-immunoreactivity (ACE2-IR) was expressed by the mucosal epithelial cells of the GIT and by the enteric neurons. […] In the cats, ACE2-IR was also expressed by the smooth muscle cells of the blood vessels and the tunica muscularis. […] The expression of the ACE2 receptor in enteric neurons may support the potential neurotropic properties of SARS-CoV-2. […] Although the evidence of ACE2-IR in the feline GIT does not necessarily indicate the possibility of viral replication and SARS-CoV-2 spread with stool, the findings in the present study could serve as an anatomical basis for additional studies considering the risk of the SARS-CoV-2 fecal-oral transmission between cats/felids, and between cats/felids and humans.
32903864 Two proposed mechanisms are liver injury mediated by angiotensin-converting enzyme 2 (ACE2) and the involvement of the systemic immune response. […] Conclusions: Due to the infrequency of viremia, ACE2-mediated viral hepatitis does not seem to account for the commonly observed liver disorders in COVID-19 patients.
32904785 Previous reports using structural analysis of the viral spike protein (S) binding its cell receptor of angiotensin-converting enzyme 2 (ACE2), indicate a broad potential of SARS-CoV2 susceptibility in wild and particularly domestic animals. […] Through integration of key immunogenetic factors, including the existence of S-binding-void ACE2 isoforms and the disparity of ACE2 expression upon early innate immune response, we further refine the SARS-CoV2 susceptibility prediction to fit recent experimental validation. […] In addition to showing a broad susceptibility potential across mammalian species based on structural analysis, our results also reveal that domestic animals including dogs, pigs, cattle and goats may evolve ACE2-related immunogenetic diversity to restrict SARS-CoV2 infections. […] Findings may relieve relevant public concerns regarding COVID-19-like risk in domestic animals, highlight virus-host coevolution, and evoke disease intervention through targeting ACE2 molecular diversity and interferon optimization.
32905022 The SARS-CoV-2 human cell receptor ACE2 has recently received extensive attention for its role in SARS-CoV-2 infection. […] Many studies have also explored the association between ACE2 and cancer. […] However, a systemic investigation into associations between ACE2 and oncogenic pathways, tumor progression, and clinical outcomes in pan-cancer remains lacking. […] Using cancer genomics datasets from the Cancer Genome Atlas (TCGA) program, we performed computational analyses of associations between ACE2 expression and antitumor immunity, immunotherapy response, oncogenic pathways, tumor progression phenotypes, and clinical outcomes in 13 cancer cohorts. […] We found that ACE2 upregulation was associated with increased antitumor immune signatures and PD-L1 expression, and favorable anti-PD-1/PD-L1/CTLA-4 immunotherapy response. […] ACE2 expression levels inversely correlated with the activity of cell cycle, mismatch repair, TGF-β, Wnt, VEGF, and Notch signaling pathways. […] Moreover, ACE2 expression levels had significant inverse correlations with tumor proliferation, stemness, and epithelial-mesenchymal transition. […] ACE2 upregulation was associated with favorable survival in pan-cancer and in multiple individual cancer types. […] These results suggest that ACE2 is a potential protective factor for cancer progression.
32905551 In the aftermath of the emergence of the coronavirus disease 2019 (COVID-19) pandemic, initial data raised concerns that ACE/ARB use can increase the expression of ACE2 receptors, leading to the worsening of COVID-19.
32905655 During infection, SARS-CoV-2 via its binding target ACE2 and TMPRSS2 can disrupt mitochondrial function.
32905794 Here, we show that polyP efficiently inhibits the binding of the envelope spike (S)-protein of the coronavirus SARS-CoV-2, the causative agent of COVID-19, to its host cell receptor ACE2 (angiotensin-converting enzyme 2). […] Applying a binding assay, soluble Na-polyP (sizes of 40 Pi and of 3 Pi units) as well as silica-nanoparticle-associated polyP significantly inhibit the interaction of the S-protein with ACE2 at a concentration of 1 µg/mL, close to the level present in blood.
32905851 Increased expression of ACE2 in young people may facilitate virus infection, while limiting inflammation and reducing the risk of severe disease.
32905897 The severity of COVID-19 may be influenced by a counterbalance between the angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2). […] SARS-CoV2 cleaves with ACE2 and enters cells leaving an unopposed effect of ACE in the lungs. […] The sex-dependent positive correlation between male 2D:4D and CFR is independent of ACE I/II, suggesting that the sex-dependent variation in the ACE2 gene may also influence the 2D:4D phenotype.
32907861 Targeting the interaction between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and the human angiotensin-converting enzyme 2 (ACE2) receptor is a promising therapeutic strategy. […] Computer-generated scaffolds were either built around an ACE2 helix that interacts with the spike receptor binding domain (RBD) or docked against the RBD to identify new binding modes, and their amino acid sequences were designed to optimize target binding, folding, and stability.
32908071 Herein, we review the role of angiotensin-converting enzyme 2 (ACE2) expression in disease progression, its association with comorbidities and COVID-19, and summarize the clinical evidence for several potential directions for future research work on ACEIs/ARBs in COVID-19 patients.
32908574 The structural research on the receptor recognition by SARS-CoV-2 has identified the key interactions between SARS-CoV-2 spike protein and its host (epithelial cell) receptor, also known as angiotensin-converting enzyme 2 (ACE2).
32909725 These findings are consistent with abnormally increased renal sodium reabsorption, possibly caused by increased angiotensin II activity secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced downregulation of angiotensin-converting enzyme 2 (ACE2) receptors.
32910704 However, it has been speculated that ACE2 receptors are responsible for the pathogenesis of adipose tissue overgrowth and may be a potential danger in terms of the relationship between ACE2 receptors and COVID19.
32911874 The expression of ACE2, a host cell receptor for SARS-CoV-2, was sustained during the development of brain organoids, especially in the somas of mature neurons, while remaining rare in neural stem cells. […] However, pseudotyped SARS-CoV-2 was observed in the axon of neurons, which lack ACE2.
32912711 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry is facilitated by interaction with Angiotensin Converting Enzyme-2 (ACE2) and possible polymorphisms in ACE2 can be a determining factor in host-viral protein interaction. […] In this review, the possible effects of ACE2 polymorphisms on SARS-CoV-2 entry along with the escalation of ‘telemedicine’ is discussed. […] An expansive literature search using keywords: “COVID-19”, “SARS-CoV-2”, “diabetes”, “type 2 diabetes’’,”type 1 diabetes“,”ACE2“,”polymorphism“,”DPP4" and “telemedicine” was conducted on Pubmed and EMBASE till 7th August 2020. […] Possible polymorphisms in ACE2 gene can play a role in influencing the virus entry in host body. […] So far, the in-silico studies involving human ACE2-viral Spike (S) interaction showed inconsistent predictions regarding some SNPs.
32912894 SARS-CoV-2, the virus responsible for COVID-19, binds to the ACE2 receptors. […] ACE2 is thought to counterbalance ACE in the renin-angiotensin system.
32913009 However, recent studies highlight the potential for IFNs to enhance expression of host angiotensin-converting enzyme 2 (ACE2), suggesting that IFN therapy or natural coinfections could exacerbate COVID-19 by upregulating this critical virus entry receptor. […] Using a cell line model, we found that beta interferon (IFN-β) strongly upregulated expression of canonical antiviral ISGs, as well as ACE2 at the mRNA and cell surface protein levels. […] Strikingly, IFN-λ1 upregulated antiviral ISGs, but ACE2 mRNA was only marginally elevated and did not lead to detectably increased ACE2 protein at the cell surface. […] IFN-γ induced the weakest ISG response but clearly enhanced surface expression of ACE2. […] Our data imply that type-specific mechanisms or kinetics shape IFN-enhanced ACE2 transcript and cell surface levels but that the antiviral action of IFNs against SARS-CoV-2 counterbalances any proviral effects of ACE2 induction. […] Nevertheless, IFNs can have undesirable side effects, and recent reports indicate that IFNs upregulate the expression of host ACE2 (a critical entry receptor for SARS-CoV-2), raising the possibility that IFN treatments could exacerbate COVID-19. […] Here, we studied the antiviral- and ACE2-inducing properties of different IFN types in both a human lung cell line model and primary human bronchial epithelial cells. […] We observed differences between IFNs with respect to their induction of antiviral genes and abilities to enhance the cell surface expression of ACE2. […] Nevertheless, all the IFNs limited SARS-CoV-2 replication, suggesting that their antiviral actions can counterbalance increased ACE2.
32913273 Competitive ligand-binding experiments suggest that the sdAbs either completely block or significantly inhibit the association between SARS-CoV-2 RBD and viral entry receptor ACE2.
32913304 With age, expression of the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) was increased in the pulmonary alveolar epithelial barrier, cardiomyocytes, and vascular endothelial cells. […] We found that interleukin 7 (IL7) accumulated in aged cardiopulmonary tissues and induced ACE2 expression in human vascular endothelial cells in an NF-κB-dependent manner. […] Furthermore, treatment with vitamin C blocked IL7-induced ACE2 expression.
32914690 The layer dependent inhibitory effect of graphene nanosheets on spike receptor-binding domain of 6LZG, complexed with host receptor i.e. angiotensin-converting enzyme 2 (ACE2) of SARS-CoV-2 was investigated through computational study.
32915473 The gold metallodrugs were effective inhibitors of the interaction of the SARS-CoV-2 spike protein with the angiotensin converting enzyme 2 (ACE2) host receptor and might thus interfere with the viral entry process.
32915649 Finally, molecular docking simulations were performed to study matrine-Mpro, matrine-ACE2, and matrine-RdRp interactions.
32915959 Therefore, we investigated the role of intestinal inflammation on the viral intestinal entry mechanisms, including ACE2, in IBD. […] In inflamed CD ileum, ACE2 was significantly decreased compared to control ileum (p=4.6E-07), whereas colonic ACE2 was higher in inflamed colon of CD/UC compared to control (p=8.3E-03; p=1.9E-03). […] Sc-RNA sequencing confirmed this ACE2 dysregulation, and exclusive epithelial ACE2 expression. […] Network analyses highlighted HNF4A as key regulator of ileal ACE2, while pro-inflammatory cytokines and interferon regulating factors regulated colonic ACE2. […] Inflammatory stimuli upregulated ACE2 in UC organoids (p=1.7E-02), not in non-IBD controls (p=9.1E-01). […] Anti-TNF therapy restored colonic ACE2 regulation in responders. […] HNF4A, an IBD susceptibility gene, seems an important upstream regulator of ACE2 in ileum, whereas interferon signaling might dominate in colon.
32916258 The SARS-CoV-2 enters into the host by the ACE2 receptor. […] Thus, ACE2 is the key to understand the mechanism of SARS-CoV-2 infection. […] However, the lack of knowledge about the biomarker of COVID-19 warrants the development of ACE2 biomarkers. […] The analysis of ACE2 expression in lung cancer was performed using The Cancer Genome Atlas (TCGA). […] Finally, we compared the mRNA expression of ACE2 and its co-expressed proteins using the TCGA. […] The up-regulation of ACE2 in lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) was found irrespective of gender and age. […] We found the low survival rate in high expression of ACE2 in lung cancer patients and 16 mutational positions. […] The common genes performed the mRNA expression in lung cancer, which proved the ACE2 is the best potential biomarker compared to co-expressed genes. […] We identified ACE2 and also its co-expressed proteins are the potential biomarker and therapy as the current COVID-19 disease and lung cancer.
32916377 Many key residues, which mediate the interaction between SARS-CoV2 spike glycoprotein (S protein) and human ACE2 receptor, have been reviewed using the SARS-CoV2 S spike protein with human ACE2 complex. […] The initial SARS-CoV2 S protein and ACE2 protein complex structure is formed by RBD structure of SARS-CoV2 S protein and ACE2 protein. […] However, the cryo-EM structure study targeting SARS-Cov S protein with human ACE2 complex has shown that there exist different binding conformations during the binding process facing ACE2 protein. […] In this study, we built a full-length SARS-CoV2 S protein with human ACE2 complex by computational methods. […] Residues K31, H34, E35 in ACE2 protein were showed both in our full-length model and RBD structure model, which recognized as critical residues in previous studies. […] Surprisingly, ACE2 residues E564, R559, N556 were only found participating in the interaction of our full-length model, which suggested the full-length model has bigger binding interface. […] In computational level, we present a stronger binding model containing a full-length structure of SARS-CoV2 S protein with ACE2 complex.
32917282 Out of 22 eligible articles that investigated candidate genes (2 as associated with COVID-19), the top-ranked genes in the number of studies were ACE2, CLEC4M (L-SIGN), MBL, MxA (n = 3), ACE, CD209, FCER2, OAS-1, TLR4, TNF-α (n = 2).
32917283 Several studies suggested that genetic variants in the ACE2 gene may influence the host susceptibility or resistance to SARS-CoV-2 infection according to the functional role of ACE2 in human pathophysiology. […] We therefore investigated the occurrence of ACE2 variants in a cohort of 131 Italian unrelated individuals clinically diagnosed with COVID-19 and in an Italian control population, to evaluate a possible allelic association with COVID-19, by direct DNA analysis. […] As a pilot study, we analyzed, by whole-exome sequencing, genetic variants of ACE2 gene in 131 DNA samples of COVID-19 patients hospitalized at Tor Vergata University Hospital and at Bambino Gesù Children’s Hospital, Rome. […] Our results suggest that there is no strong evidence, in our cohort, of consistent association of ACE2 variants with COVID-19 severity. […] We might speculate that rare susceptibility/resistant alleles could be located in the non-coding regions of the ACE2 gene, known to play a role in regulation of the gene activity.
32917722 Mechanistically, we demonstrate that sphingosine binds to ACE2, the cellular receptor of SARS-CoV-2, and prevents the interaction of the receptor binding domain of the viral spike protein with ACE2.
32917884 The novel coronavirus SARS-CoV-2 entry into host cells is mediated by its spike glycoprotein (S-glycoprotein), and the angiotensin-converting enzyme 2 (ACE2) has been identified as a cellular receptor. […] Here, we use atomic force microscopy to investigate the mechanisms by which the S-glycoprotein binds to the ACE2 receptor. […] We demonstrate, both on model surfaces and on living cells, that the receptor binding domain (RBD) serves as the binding interface within the S-glycoprotein with the ACE2 receptor and extract the kinetic and thermodynamic properties of this binding pocket.
32918944 The cellular receptor for SARS-CoV-2 is the Angiotensin Converting Enzyme (ACE2). […] In this study, we used several bioinformatics approaches to bring clues in the interaction of ACE2, TMPRSS2, and GRP78 with SARS-CoV-2. […] Results showed that ionic pairs (salt bridges, N-O pair, and long-range interactions) produced between ACE2 and the viral spike has an essential function in the host interaction.
32919067 Protein S binds to angiotensin-converting-enzyme 2, ACE2, of the host cell, followed by proteolysis of the spike protein, drastic protein conformational change with exposure of the fusion peptide of the virus, and entry of the virion into the host cell.
32920291 The objective of this study is to investigate whether CQ and HCQ could be ACE2 blockers and used to inhibit 2019-nCoV virus infection. […] In our study, we used CCK-8 staining, flow cytometry and immunofluorescent staining to evaluate the toxicity and autophagy of CQ and HCQ, respectively, on ACE2 high-expressing HEK293T cells (ACE2h cells). […] We further analyzed the binding character of CQ and HCQ to ACE2 by molecular docking and surface plasmon resonance (SPR) assays, 2019-nCoV spike pseudotyped virus was also used to observe the viropexis effect of CQ and HCQ in ACE2h cells. […] Results showed that HCQ is slightly more toxic to ACE2h cells than CQ. […] Both CQ and HCQ could bind to ACE2 with KD = (7.31 ± 0.62)e-7 M and (4.82 ± 0.87)e-7 M, respectively. […] They exhibit equivalent suppression effect for the entrance of 2019-nCoV spike pseudotyped virus into ACE2h cells. […] CQ and HCQ both inhibit the entrance 2019-nCoV into cells by blocking the binding of the virus with ACE2.
32921216 Abbreviations: ICU: An intensive care unit; 2019-nCoV: 2019 novel coronavirus; ACEI: ACE inhibitor; ACS: Acute coronary syndrome; ARDS: Acute respiratory distress syndrome; AT1R: Ang II type 1 receptor; ATP: Adenosine triphosphate; ACC: American College of Cardiology; ACE: Angiotensin converting enzyme; Ang II: Angiotensin II; ARB: Angiotensin II receptor blocker; AV block: Atrioventricular block; CAD: Coronary artery disease; CVD: Cardiovascular disease; CT: Computerized tomography; CHF: Congestive heart failure; CHD: Coronary heart disease; CK-MB: Creatine kinase isoenzyme-MB; CRP: C-reactive protein; cTnI: Cardiac troponin I; EAT: Epicardial adipose tissue; ECMO: Extracorporeal membrane oxygenation; FDA: Food and Drug Administration; G-CSF: Granulocyte colony-stimulating factor; HFrEF: HF with a reduced ejection fraction; synhACE2: Human isoform of ACE2; IL: Interleukin; IABP: Intra-aortic balloon counterpulsation; IP10: Interferon γ-induced protein 10 kDa; LPC: Lysophosphatidylcholine; Mas: Mitochondrial assembly receptor; MCP1: Monocyte chemoattractant protein-1; MERS: Middle East respiratory syndrome; MIP1a: macrophage inflammatory protein 1a: MOF: Multiple organ failure; MI: Myocardial infarction; MRI: Magnetic resonance imaging; MYO: Myohe-moglobin; NT-proBNP: N-terminal pro-brain natriuretic peptide; PCPS: Percutaneous cardiopulmonary assistance; rhACE2: Recombinant human ACE2; SARS: Severe acute respiratory syndrome; Th: T helper; RAS: Renin-angiotensin system; TNF-α: Tumor necrosis factor-α; WHO: World Health Organization.
32921279 These reports have influenced us to perform a comparative analysis among angiotensin-converting enzyme 2 (ACE2) homologous proteins for verifying the conservation of specific protein regions. […] One of the most conserved peptides is represented by the peptide "353-KGDFR-357 (H. sapiens ACE2 residue numbering), which is located on the surface of the ACE2 molecule and participates in the binding of SARS-CoV-2 spike receptor binding domain (RBD). […] Multiple sequence alignments of the ACE2 proteins by ClustalW, whereas the three-dimensional structure of its binding region for the spike glycoprotein of SARS-CoV-2 was assessed by means of Spanner, a structural homology modeling pipeline method. […] ACE2 works as a receptor for the SARS-CoV-2 spike glycoprotein between humans, dogs, cats, tigers, minks, and other animals, except for snakes. […] The three-dimensional structure of the KGDFR hosting protein region involved in direct interactions with SARS-CoV-2 spike RBD of the mink ACE2 appears to form a loop structurally related to the human ACE2 corresponding protein loop, despite of the reduced available protein length (401 residues of the mink ACE2 available sequence vs 805 residues of the human ACE2). […] The multiple sequence alignments of the ACE2 proteins shows high homology and complete conservation of the five amino acid residues: 353-KGDFR-357 with humans, dogs, cats, tigers, minks, and other animals, except for snakes.
32921715 There are several reasons, including the prolonged hospitalization time as a consequence of their more severe illness and aberrant expression of angiotensin-converting enzyme 2 (ACE2) - the cell surface receptor of SARS-COV2 that is present on cardiac cells - and using drugs such as ACE inhibitors and angiotensin receptor blockers (ARBs) that alter the expression of ACE2.
32921739 It has been shown that SARS-CoV2 binds to ACE2. […] Covid-19 may infect NK cells to suppress their functions, as NK cells express angiotensin converting enzyme 2 (ACE2).
32922297 SARS-CoV-2 binds the angiotensin-converting enzyme 2 (ACE2) on the cell surface and this complex is internalized. […] ACE2 serves as an endogenous inhibitor of inflammatory signals associated with four major regulator systems: the renin-angiotensin-aldosterone system (RAAS), the complement system, the coagulation cascade, and the kallikrein-kinin system (KKS).
32923747 This organ expressed angiotensin-converting enzyme 2 (ACE2), the transmembrane protein which facilitate the entering of the virus into the cell. […] Previous studies showed ACE2 role in various indications of this disease, especially in kidney effects. […] The MicroRNAs (miRNAs) in this organ affected ACE2 expression. […] Several miRNAs, particularly miR-18 (which was upregulated in nephropathy), played a crucial role in ACE2 expression. […] Therefore, the antimiR-18 roles were summarized in various primate models that aided in developing the therapy for ACE2 related diseases.
32924827 The results showed 97% sequence similarity among SARS and SARS-CoV-2 main protease and has same cleavage site positions and ACE2 receptor binding region as in the SARS-CoV spike protein.
32926272 This novel CoV enters the cells through the angiotensin-converting enzyme 2 (ACE2) receptor.
32926917 By making use of its spike (S) protein, the virus binds to its primary human cell receptor, angiotensin converting enzyme 2 (ACE2) which is present in the pulmonary epithelial cells as well as other organs. […] SARS-CoV-2 may cause a downregulation of ACE2. […] ACE2 plays a protective role in the pulmonary system through its Mas-receptor and alamandine-MrgD-TGR7 pathways. […] An attractive strategy in SARS-CoV-2 therapeutics would be to augment ACE2 either directly by supplementation or indirectly through drugs which increase its levels or stimulate its downstream players. […] In this semi-systematic review, we have analysed the pathophysiological interplay between ACE and ACE2 in the cardiopulmonary system, the modulation of these two proteins by SARS-CoV-2, and potential therapeutic avenues targeting ACE-Ang II and ACE2-Ang (1-7) axes, that can be utilized against COVID-19 disease progression.
32927621 X-ray crystallography and cryo-electron microscopy made huge impact on the studies on the S protein and ACE2 receptor protein interaction, by elucidating the three-dimensional structures of these proteins and their conformational changes.
32928868 To review evidence on routinely prescribed drugs in the UK that could upregulate or downregulate ACE2 and potentially affect COVID-19 disease. […] Any design with animal or human models examining a currently prescribed UK drug compared with a control, placebo or sham group, and reporting an effect on ACE2 level, activity or gene expression. […] We screened 3360 titles and included 112 studies with 21 different drug classes identified as influencing ACE2 activity. […] Ten studies were in humans and one hundred and two were in animal models None examined ACE2 in human lungs. […] Our review indicates that the impact of currently prescribed drugs on ACE2 has been poorly studied in vivo, particularly in human lungs where the SARS-CoV-2 virus appears to enact its pathogenic effects.
32928903 SARS-CoV-2 shows a high affinity to ACE2 receptors, making sites of high ACE2 receptor expression, such as lungs, GI tract, brain, kidneys, heart, liver and immune system, a prime target for infection.
32929138 The 3D structures show that the protein surface is extensively shielded from antibody recognition by glycans, with the notable exception of the ACE2 receptor binding domain, and also that the degree of shielding is largely insensitive to the specific glycoform.
32929412 SARS-CoV-2 mode of actions includes hyper-inflammation characterized by a severe and fatal hyper-cytokinaemia with multi-organ failure; immunosuppression; reduction of angiotensin-converting enzyme 2 (ACE2) to enhance pulmonary vascular permeability causing damage to the alveoli; and further activated by open reading frame (ORF)3a, ORF3b, and ORF7a via c-Jun N- terminal kinase (JNK) pathway which induces lung damage.
32930058 Like other coronaviruses, SARS-CoV-2 relies on the surface Spike glycoprotein to access the host cells, mainly through the interaction of its Receptor Binding Domain (RBD) with the host receptor Angiotensin-Converting Enzyme2 (ACE2). […] Therefore, molecular entities able to interfere with binding of the SARS-CoV-2 Spike protein to ACE2, or damping hyperinflammatory cytokines storm, blocking ERK1/2 phosphorylation have a great potential to inhibit viral entry along with viral infectivity. […] Notably, virtual docking and simulation data also suggest LDN may disrupt the interaction of ACE2 with RBD.
32930095 Adipose tissue demonstrates high expression of ACE2 which SARS- CoV-2 exploits to enter host cells. […] Acute viral infection results in ACE2 downregulation. […] This relative deficiency can lead to disturbances in other systems controlled by ACE2, including the renin-angiotensin system. […] Here, we propose that interactions of virally-induced ACE2 deficiency with obesity and/or diabetes leads to a synergistic further impairment of endothelial and gut barrier function.
32930394 Immunohistochemistry for the receptor of the SARS-COV 2, ACE2, and its priming activatorTMPRSS2 revealed that both proteins co-localize in airway cells. […] In particular, the ACE2 protein was expressed in both endothelial cells and alveolar type I and II pneumocytes in the areas of histological diffuse alveolar damage (DAD).
32934757 Our present study showed that angiotensin-converting enzyme-2 (ACE2), a cellular receptor for SARS-CoV-2, is expressed in human induced pluripotent stem cell (iPSC)-derived neural stem/progenitor cells (hiPSC-NS/PCs) and young neurons. […] Considering the role of CCN1 which is known to be involved in viral toxicity and inflammation, hiPSC-NS/PCs could provide an excellent model for COVID-19-associated CNS disorders from the aspect of SARS-CoV-2 infection-ACE2-CCN1 axis.
32934806 Methods: Inhibition of angiotensin-converting enzyme 2 (ACE2) caused by the spike protein of SARS-CoV-2 is the most plausible mechanism of lung injury in COVID-19. […] We performed drug repositioning analysis to identify drug candidates that reverse gene expression pattern in L1000 lung cell line HCC515 treated with ACE2 inhibitor. […] Further bioinformatics analysis shows that 12 significantly enriched pathways (P-value <0.05) overlap between HCC515 cells treated with ACE2 inhibitor and human COVID-19 patient lung tissues. […] Conclusions: This study shows that ACE2 inhibition is likely part of the mechanisms leading to lung injury in COVID-19, and that compounds such as COL-3 and CGP-60474 have potential as repurposed drugs for its treatment.
32936429 A tentative hypothesis to explain these findings is the role of angiotensin-converting enzyme 2 (ACE2) and serine protease TMPRSS2 involved in viral infection. […] In this review, we summarize the available evidence pointing to gender-related differences in ACE2 and TMPRSS2 expression, from both genetic and endocrine points of view. […] Altogether, available evidence points toward two not-mutually exclusive mechanisms in gender susceptibility to COVID-19 by sex hormonal regulation of ACE2 and TMPRSS2. […] On one hand, ACE2 expression could be increased in women, either by estrogens or constitutively by X chromosome inactivation escape or by reduced methylation, providing a larger reservoir of ACE2 to maintain the fundamental equilibrium of RAS regulatory axis. […] On the other, low levels of androgens in women may keep at low levels TMPRSS2 expression, representing a further protective factor for the development of COVID-19 infection, despite the increased expression of ACE2, which represents the Trojan horse for SARS-CoV-2 entry.
32936531 The SARS-CoV-2 makes its way into the cell via the ACE2 receptor and the proteolytic action of TMPRSS2. […] What is known about the expression and epigenetic regulation of the ACE2 gene and the various players in the host response are explored in this review.
32936832 It was shown that the human Angiotensin-converting enzyme 2 (ACE2) is the receptor of recent coronavirus SARS-CoV-2, and variation in this gene may affect the susceptibility of a population. […] Therefore, we have analysed the sequence data of ACE2 among 393 samples worldwide, focusing on South Asia. […] In the present analyses of ACE2, we observed that the majority of South Asian haplotypes are closer to East Eurasians rather than to West Eurasians.
32937008 Angiotensin-converting enzyme 2 (ACE2), which facilitates SARS-CoV-2 host cell entry, may be impacted by angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), two commonly used antihypertensive classes.
32937591 Bulk sequencing demonstrated that mouse, non-human primate and human olfactory mucosa expresses two key genes involved in CoV-2 entry, ACE2 and TMPRSS2. […] However, single cell sequencing revealed that ACE2 is expressed in support cells, stem cells, and perivascular cells, rather than in neurons. […] Immunostaining confirmed these results and revealed pervasive expression of ACE2 protein in dorsally-located olfactory epithelial sustentacular cells and olfactory bulb pericytes in the mouse.
32938700 Here, we present an efficient, competitive serological assay that can simultaneously determine an individual’s seroreactivity against the SARS-CoV-2 Spike protein and determine the proportion of anti-Spike antibodies that block interaction with the human angiotensin-converting enzyme 2 (ACE2) required for viral entry. […] Sera are then competed with soluble ACE2-Fc, or with a higher-affinity variant thereof, to determine the proportion of ACE2 blocking anti-RBD antibodies. […] Assessment of sera from 144 SARS-CoV-2 patients ultimately revealed that a remarkably consistent and high proportion of antibodies in the anti-RBD pool targeted the epitope responsible for ACE2 engagement (83% ± 11%; 50% to 107% signal inhibition in our largest cohort), further underscoring the importance of tailoring vaccines to promote the development of such antibodies.IMPORTANCE With the emergence and continued spread of the SARS-CoV-2 virus, and of the associated disease, coronavirus disease 2019 (COVID-19), there is an urgent need for improved understanding of how the body mounts an immune response to the virus. […] Here, we developed a competitive SARS-CoV-2 serological assay that can simultaneously determine whether an individual has developed antibodies against the SARS-CoV-2 Spike protein receptor-binding domain (RBD) and measure the proportion of these antibodies that block interaction with the human angiotensin-converting enzyme 2 (ACE2) required for viral entry. […] Using this assay and 144 SARS-CoV-2 patient serum samples, we found that a majority of anti-RBD antibodies compete for ACE2 binding.
32938937 To this end, we collected information regarding naturally-occurring variants of the Angiotensin-converting enzyme 2 (ACE2), an epithelial receptor that both SARS-CoV and SARS-CoV-2 use to enter the host cells. […] We built 242 structural models of variants of human ACE2 bound to the receptor binding domain (RBD) of the SARS-CoV-2 surface spike glycoprotein (S protein) and refined their interfaces with HADDOCK. […] Our dataset includes 140 variants of human ACE2 representing missense mutations found in genome-wide studies, 39 mutants with reported effects on the recognition of the RBD, and 63 predictions after computational alanine scanning mutagenesis of ACE2-RBD interface residues.
32940573 SARS-CoV-2 shares genetic similarity with SARS-CoV with some modification in the S protein leading to their enhanced binding affinity toward the angiotensin-converting enzyme 2 (ACE2) receptors of human lung cells.
32940922 Cellular entry of SARS-CoV-2 depends on the binding of its spike protein to a cellular receptor named angiotensin-converting enzyme 2 (ACE2), and the subsequent spike protein-priming by host cell proteases, including transmembrane protease serine 2 (TMPRSS2). […] Thus, high expression of ACE2 and TMPRSS2 is considered to enhance the invading capacity of SARS-CoV-2. […] To elucidate the underlying histological mechanisms of the aerodigestive disorders caused by SARS-CoV-2, we investigated the expression of ACE2 and TMPRSS2 proteins using immunohistochemistry, in the aerodigestive tracts of the tongue, hard palate with partial nasal tissue, larynx with hypopharynx, trachea, esophagus, and lung of rats. […] Co-expression of ACE2 and TMPRSS2 proteins was observed in the taste buds of the tongue, nasal epithelium, trachea, bronchioles, and alveoli with varying degrees of expression. […] A wide range of organs have been speculated to be affected by SARS-CoV-2 depending on the expression levels of ACE2 and TMPRSS2.
32941783 In this article, we investigate the binding processes of a fragment of the coronavirus spike protein receptor binding domain (RBD), the hexapeptide YKYRYL on the angiotensin-converting enzyme 2 (ACE2) receptor, and its inhibitory effect on the binding and activation of the coronavirus-2 spike protein CoV-2 RBD at ACE2. […] In agreement with an experimental study, we find a high affinity of the hexapeptide to the binding interface between CoV-2 RBD and ACE2, which we investigate using 20 independent equilibrium molecular dynamics (MD) simulations over a total of 1 μs and a 200-ns enhanced correlation guided MD simulation. […] We then evaluate the effect of the hexapeptide on the assembly process of the CoV-2 RBD to ACE2 in long-time enhanced correlation guided MD simulations. […] In that set of simulations, we find that CoV-2 RBD does not bind to ACE2 with the binding motif shown in experiments, but it rotates because of an electrostatic repulsion and forms a hydrophobic interface with ACE2. […] Surprisingly, we observe that the hexapeptide binds to CoV-2 RBD, which has the effect that this protein only weakly attaches to ACE2 so that the activation of CoV-2 RBD might be inhibited in this case. […] Our results indicate that the hexapeptide might be a possible treatment option that prevents the viral activation through the inhibition of the interaction between ACE2 and CoV-2 RBD.
32941803 Electron microscopy combined with scanning mutagenesis identified ab8 interactions with all three S protomers and showed how ab8 neutralized the virus by directly interfering with ACE2 binding.
32942285 SARS-CoV-2 infection is initiated by virus binding to ACE2 cell surface receptors1-4, followed by fusion of virus and cell membranes to release the virus genome into the cell. […] We have investigated the binding of ACE2 to the furin-cleaved form of SARS-CoV-2 S by cryoEM. […] We classify ten different molecular species including the unbound, closed spike trimer, the fully open ACE2-bound trimer, and dissociated monomeric S1 bound to ACE2. […] The ten structures describe ACE2 binding events which destabilise the spike trimer, progressively opening up, and out, the individual S1 components. […] The opening process reduces S1 contacts and un-shields the trimeric S2 core, priming fusion activation and dissociation of ACE2-bound S1 monomers. […] The structures also reveal refolding of an S1 subdomain following ACE2 binding, that disrupts interactions with S2, notably involving Asp61413-15, leading to destabilisation of the structure of S2 proximal to the secondary (S2’) cleavage site.
32942748 The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus responsible for COVID-19, binds to its receptor angiotensin-converting enzyme 2 (ACE2), and replicates within the cells of the nasal cavity, then spreads along the airway tracts, causing mild clinical manifestations, and, in a majority of patients, a persisting loss of smell.
32943587 The G614 variant is associated with higher upper respiratory tract viral load, higher infectivity, increased total S protein incorporation into the virion, reduced S1 shedding and a conformational change leading to a more ACE2- binding and fusion- competent state.
32944935 Reports denote SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2) as its primary entry point into the host cell. […] Here, we used single-cell RNA sequencing data of human organoids to analyze expressions of ACE2 and TMPRSS2, in addition to an array of RNA receptors to examine their role in SARS-CoV-2 pathogenesis. […] ACE2 is abundant in all organoids, except the prostate and brain, and TMPRSS2 is omnipresent. […] Innate immune pathways are upregulated in ACE2(+) cells of all organoids, except the lungs. […] Besides this, the expression of low-density lipoprotein receptor is highly enriched in ACE2(+) cells in intestinal, lung, and retinal organoids, with the highest expression in lung organoids.
32945111 The identification of additional mechanisms involved in the endothelial damage as that described by Richardson et al. [1] mediated by the p38 MAPK pathway, which is upregulated as a result of the binding of SARSCoV2 on ACE2 receptors on the surface of endothelial cells and, in turn, activates the transcription of the proinflammatory cytokines.
32949179 ACE2 has been identified as a cell entry receptor for the virus. […] We silenced the expression of STAT3α and STAT3β, and found that while silencing STAT3α causes an increase in ACE2 expression, silencing STAT3β causes the opposite effect. […] Studying the role of STAT3 in ACE2 expression will shed light on the molecular events that contribute to the progression of the disease and that the different roles of STAT3α and STAT3β in that context must be taken in consideration.
32949888 However, we used more techniques and also included Angiotensin converting enzyme 2 (ACE2) (a SARS-CoV receptor, possibly the viral entry point in alveolar lung cells) and the immune system, as cytokine storm is essential in the late phase. […] Intersection calculations between the LHQW-proteins and ACE2 co-expression-proteins. […] LHQW shared 189 proteins with ACE2 co-expression proteins. […] Moreover, it also relieves the “cytokine storm” and improves ACE2-expression-disorder-caused symptoms.
32950044 This result is thought to be due to the anti-A antibody’s ability to block the ACE2 receptor.
32950735 Angiotensin-converting enzyme 2 (ACE2) is the receptor of the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19) pandemic. […] ACE2 has been shown to be down-regulated during coronaviral infection, with implications for circulatory homeostasis. […] Despite the loss of ACE2 and raised circulating vasoconstrictor angiotensin II (AngII), COVID-19 patients experience a vasodilative vasculopathy. […] This article discusses the interplay between the immune system and pulmonary vasculature and how SARS-CoV-2-mediated ACE2 disruption and AngII may contribute to the novel vascular pathophysiology of COVID-19.
32953401 In the heart, expressed angiotensin-converting enzyme 2 (ACE2) and response effect of hyperactivity with angiotensin II associated to the renin-angiotensin mechanism are key factors of hypertension, atherosclerosis, and congestive heart failure.
32955126 The receptor for spike protein of SARS-CoV-2, angiotensin 2 converting enzyme (ACE2), and transmembrane protease serine (for viral entry) is expressed in upper gastrointestinal (GI) enterocytes, ACE2 is expressed on enteroendocrine cells (EECs), and SARS-CoV-2 infects enterocytes but not EECs (studies needed with native EECs). […] Additionally, data from SARS-CoV-2 show an increase in plasma angiotensin II (consequent on SARS-CoV-2/ACE2 interaction), a centrally (AP) acting emetic, providing a further potential mechanism in COVID-19.
32956843 SARS-CoV-2 intervened mainly in the lung with progression to pneumonia and acute respiratory distress syndrome (ARDS) via the angiotensin-converting enzyme 2(ACE2) receptor. […] Depending on the viral load, infection spread through the ACE2 receptor further to various organs such as heart, liver, kidney, brain, endothelium, GIT, immune cell, and RBC (thromboembolism).
32957797 The gene is Angiotensin I Converting-Enzyme 2 (ACE2). […] According to the multi-experiment matrix (MEM), the gene exhibiting the most statistically significant co-expression link to ACE2 is Dopa Decarboxylase (DDC). […] SARS-CoV2-induced downregulation of ACE2 expression might reduce dopamine and serotonin synthesis, causing hypodopaminergia.
32957884 Previous studies have shown that quercetin reduces the entry of the virus into the cell by blocking the ACE2 receptor, as well as reducing the level of interleukin-6 in SARS and MERS patients.
32957894 The present review focuses on the role of S-spike protein in COVID-19 which helps the virus intruder the enzyme ACE2 (angiotensin-converting enzyme 2).
32958580 LA binding stabilizes a locked S conformation giving rise to reduced ACE2 interaction in vitro.
32959144 To visualize SARS-CoV-2 host receptors ACE2 and CD147 on human oocytes and blastocysts. […] SARS-CoV-2 host receptors ACE2 and CD147 are present on the membrane of trophectoderm, epiblast and hypoblast cells in human blastocysts.
32960159 Network analysis revealed a set of genes/proteins, highly dense genes/protein clusters and sub-networks of Angiotensin-converting enzyme 2 (ACE2), Helicase, spike (S) protein (trimeric), membrane (M) protein, envelop (E) protein, and the nucleocapsid (N) protein. […] Further, molecular dynamics simulation of critical proteins such as ACE2, Mpro and spike proteins are performed to elucidate the inhibition mechanism. […] The binding energy which largely arises from van der Waals interactions is calculated (ACE2=-50.21 ± 6.3, Mpro=-89.50 ± 6.32 and spike=-23.06 ± 4.39) through molecular mechanics Poisson-Boltzmann surface area also confirm the affinity of procyanidin towards the critical receptors.
32961082 The spike (S) glycoprotein mediates binding to the angiotensin-converting enzyme 2 (ACE2) receptor for virus entry and also services as the target of virus-neutralizing antibodies, making it an attractive and leading viral antigen for vaccine development.
32962613 In general, all CoVs including SARSCoV-2 are spherical positive single-stranded RNA viruses containing spike (S) protein, envelope (E) protein, nucleocapsid (N) protein, and membrane (M) protein, where S protein has a receptor-binding domain (RBD) that mediates the binding to host cell receptor, angiotensin converting enzyme 2 (ACE2).
32964551 In this study, one hundred (100) A. melegueta secondary metabolites have been mined and computational evaluated for inhibition of host furin, and SARS-COV-2 targets including 3C-like proteinase (Mpro /3CLpro), 2’-O-ribose methyltransferase (nsp16) and surface glycoprotein/ACE2 receptor interface.
32964684 Literature reports that angiotensin-converting enzyme 2 (ACE2) is the host receptor mediating the cell entry of severe acute respiratory syndrome coronavirus 2. […] Clinical and experimental evidence shows that loss of function of ACE2 aggravates pulmonary hypertension and gain of function of ACE2 exerts protection on cardiopulmonary circulation.
32964802 Angiotensin converting enzyme 2 (ACE2) is a receptor protein that interacts with the spike glycoprotein of the host to facilitate the entry of coronavirus (SARS-CoV-2) hence causing the disease (COVID-19). […] The interaction of wildtype ACE2-spike glycoprotein and their variants were analyzed using docking studies. […] The mutations W461R, G405E and F588S in ACE2 receptor protein and population specific mutations P391S, C12S and G1223A in the spike glycoprotein were predicted as highly destabilizing to the structure of the bound complex. […] So far, no extensive in silico study has been reported that identifies the effect of SNPs on Spike glycoprotein-ACE2 interaction exploring both sequence and structural features.
32965016 This virus can enter human cells through angiotensin-converting enzyme 2 (ACE2) in alveoli and activate immune response in human body.
32965603 Considerable concern has emerged for the potential harm in the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor inhibitors (ARBs) in COVID-19 patients, given that ACEIs and ARBs may increase the expression of ACE2 receptors that represent the way for coronavirus 2 to entry into the cell and cause severe acute respiratory syndrome.
32965660 SARS-CoV-2 enters cells by interaction between SARS-CoV-2 spike protein and the receptor molecule angiotensin converting enzyme 2 (ACE2) expressed on the surface of the target cells, such that polymorphisms and the expression level of ACE2 influence infectivity and consequent pathogenesis of SARS-CoV-2.
32966582 Infection of iPS-CMs was dependent on cathepsins and angiotensin-converting enzyme 2 (ACE2), and was blocked by remdesivir. […] This study demonstrates that SARS-CoV-2 infects cardiomyocytes in vitro in an ACE2- and cathepsin-dependent manner.
32966801 ACE2 binds the coronavirus SARS-CoV-2 and facilitates its cellular entry. […] Interferons activate ACE2 expression in pneumocytes, suggesting a critical role of cytokines in SARS-CoV-2 target cells. […] Viral RNA was detected in breast milk in at least seven studies, raising the possibility that ACE2 is expressed in mammary tissue during lactation. […] Here, we show that Ace2 expression in mouse mammary tissue is induced during pregnancy and lactation, which coincides with the activation of intronic enhancers. […] Deletion of Stat5a results in decommissioning of the enhancers and an 83% reduction of Ace2 mRNA. […] We also demonstrate that Ace2 expression increases during lactation in lung, but not in kidney and intestine.
32966970 A key step in understanding the pathobiology of the SARS-CoV-2 was the identification of -converting enzyme 2 (ACE2) as the receptor for SARS-CoV-2 to gain entry into host cells. […] ACE2 is an established component of the ‘protective arm’ of the renin-angiotensin-aldosterone-system (RAAS) that opposes ACE/angiotensin II (ANG II) pressor and tissue remodelling actions. […] Identification of ACE2 as the entry point for SARS-CoV-2 into cells quickly focused attention on the use of ACE inhibitors (ACEi), angiotensin receptor blockers (ARB) and mineralocorticoid receptor antagonists (MRA) in patients with hypertension and cardiovascular disease given that these pharmacological agents upregulate ACE2 expression in target cells. […] ACE2 is cleaved from the cells by metalloproteases ADAM10 and ADAM17. […] This review will examine the endocrine mechanisms that control ACE2 and discusses the impact of therapies targeting the RAAS, glucocorticoid and other endocrine systems for their relevance to the impact of SARS-CoV-2 infection and the treatment and recovery from COVID-19-related critical illness.
32967280 Angiotensin converting enzyme 2 (ACE2) downregulation is a key negative factor for the severity of lung edema and acute lung failure observed in patients infected with SARS-CoV-2. […] ACE2 downregulation affects the levels of diverse peptide mediators of the renin-agiotensin-aldestosterone and kallikrein-kinin systems, compromising vascular hemostasis.
32967703 SARS-coronavirus-2 enters host cells through binding of the Spike protein to ACE2 receptor and subsequent S priming by the TMPRSS2 protease. […] We aim to assess differences in both ACE2 and TMPRSS2 expression in normal tissues from oral cavity, pharynx, larynx and lung tissues as well as neoplastic tissues from the same areas.
32968552 This virus uses angiotensin converting enzyme 2 (ACE2) receptors to facilitate cellular entry. […] ACE2 receptors appear to be highly expressed in pancreatic exocrine glands and islet cells, more so than in lung tissues, suggesting that pancreatic injury can occur despite having only mild COVID-19 symptoms.
32968645 Coronavirus disease (COVID-19) is a severe infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that binds to the cells; angiotensin converting enzyme 2 (ACE2) receptor. […] Imbalance in the ACE2-RAAS- bradykinin axis and the cytokine storm could be an important mechanism leading to pathophysiological changes in pulmonary vascular and secondary refractory hypoxemia.
32968798 Angiotensin-converting enzyme 2 (ACE2) plays a key role in the host cells as a receptor of Spike-I Glycoprotein of COVID-19 which causes final infection. […] ACE2 is highly expressed in the bladder, ileum, kidney and liver, comparing with ACE2 expression in the lung-specific pulmonary alveolar type II cells. […] In this study, the single-cell RNAseq data of the five tissues from different humans are curated and cell types with high expressions of ACE2 are identified. […] Firstly, renin-angiotensin system and PPAR signaling pathway can play a vital role for enhancing the infection after its intrusion through ACE2.
32969123 Biological plausibility for infection with SARS-CoV-2 exists in testis, ovaries, and placenta as they express ACE2 receptor activity. […] In females, an alteration of the ACE2 cascade via SARS-CoV-2 infection could lead to impairment in important follicular and luteal processes.
32969333 It was proven that human ACE2 is the main receptor for the entry of Covid-19 into lower respiratory tract epithelial cells through interaction with SARS-CoV-2 S protein. […] In this study, using structure-based virtual screening of FDA databases, several lead drugs were discovered based on the ACE2-binding pocket of SARS-CoV-2 S protein.
32969768 Ectopic expression of viral receptors revealed that the levels of angiotensin-converting enzyme 2 (ACE2) expression confer permissiveness to SARS-CoV-2 infection, and TMPRSS2 greatly facilitates ACE2-mediated SARS-CoV-2 dissemination. […] Interestingly, ACE2 but not TMPRSS2 expression was significantly promoted by enterocytic differentiation, suggesting that the state of enterocytic differentiation may serve as a determining factor for viral propagation.
32970391 Here, the expression of five genes, known to encode coronavirus receptors/interactors (ACE2, TMPRSS2, CLEC4M, DPP4 and TMPRSS11D), was investigated in normal and cancer tissues, and their molecular relationships with clinical comorbidities were investigated.
32970653 Several recent studies reveal that angiotensin-converting enzyme 2 (ACE2), which was found in the target cells of the virus, is highly expressed in the lungs, small bowel, and vasculature.
32970989 We show that SARS-CoV-2 spike protein interacts with both cellular heparan sulfate and angiotensin-converting enzyme 2 (ACE2) through its receptor-binding domain (RBD). […] Docking studies suggest a heparin/heparan sulfate-binding site adjacent to the ACE2-binding site. […] Both ACE2 and heparin can bind independently to spike protein in vitro, and a ternary complex can be generated using heparin as a scaffold. […] Electron micrographs of spike protein suggests that heparin enhances the open conformation of the RBD that binds ACE2. […] On cells, spike protein binding depends on both heparan sulfate and ACE2. […] We suggest a model in which viral attachment and infection involves heparan sulfate-dependent enhancement of binding to ACE2.
32970990 Here, we report the 3.5-Å cryo-EM structure of BD-368-2/trimeric-spike complex, revealing that BD-368-2 fully blocks ACE2 recognition by occupying all three receptor-binding domains (RBDs) simultaneously, regardless of their “up” or “down” conformations.
32971150 Possible mechanisms such as a decreased expression of angiotensin-converting enzyme 2 (ACE2) and a lower virulence because of a high altitude environment, may explain this epidemiological features.
32971472 ACE2 is a host ectopeptidase and the receptor for SARS-CoV-2. […] Numerous reports describe ACE2 mRNA abundance and tissue distribution; however, mRNA abundance is not always representative of protein levels. […] Currently, there is limited data evaluating ACE2 protein and its correlation with other SARS-CoV-2 susceptibility factors. […] Our results reveal that ACE2 protein is highest within regions of the sinonasal cavity and pulmonary alveoli, sites of presumptive viral transmission and severe disease development, respectively. […] In the lung parenchyma, ACE2 protein was found on the apical surface of a small subset of alveolar type II cells and colocalized with TMPRSS2, a cofactor for SARS-CoV2 entry. […] ACE2 protein was not increased by pulmonary risk factors for severe COVID-19. […] Additionally, ACE2 protein was not reduced in children, a demographic with a lower incidence of severe COVID-19. […] These results offer new insights into ACE2 protein localization in the human respiratory tract and its relationship with susceptibility factors to COVID-19.
32972126 It is known that SARS-CoV-2 infects the host through the cell surface receptor of angiotensin-converting enzyme 2 (ACE2), which is expressed in multiple organs, and in the arterial and venous endothelial cells.
32972339 The priming of the spike (S) protein of the virus by proteolytic cleavage by the trans-membrane serine protease-2 (TMPRSS2) is necessary for fusion of the virus to the host cell after it binds to its receptor angiotensin converting enzyme-2 (ACE2).
32972994 Cryo-electron microscopy structures show that S2E12 and S2M11 competitively block ACE2 attachment and that S2M11 also locks the spike in a closed conformation by recognition of a quaternary epitope spanning two adjacent receptor-binding domains.
32973534 SARS-CoV-2 mainly invades the cells by binding to the angiotensin converting enzyme 2 (ACE2) receptor, leading to the injury of respiratory system, cardiovascular system, digestive system, and urinary system, and even secondary to acute respiratory distress syndrome (ARDS) and systemic inflammatory response, resulting in multiple organ failure.
32973818 SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) receptor and is primarily trophic for the lower and upper respiratory tract.
32973879 We explored and collected five published and one unpublished single-cell respiratory system tissue transcriptome datasets, including idiopathic pulmonary fibrosis (IPF), aging lungs (mouse origin data), lung cancers, and smoked branchial epithelium, for specifically reanalyzing the ACE2 and TMPRSS2 expression profiles. […] Compared to normal people, we found that smoking and lung cancer increase the risk for COVID-19 infection due to a higher expression of ACE2 and TMPRSS2 in lung cells.
32974030 Using the recently published crystal structure of the SARS-CoV-2 spike protein complexed with the human host cell receptor angiotensin converting enzyme 2 (ACE2), we characterized the structure and evolution of ACE2 in several of these species and identify a single interacting amino acid residue conserved between human and Felidae ACE2 but not in Canidae that correlates with virus susceptibility. […] Using computational analyses we describe how this site likely affects ACE2 targeting by the virus.
32974224 The receptor binding domain (RBD) in S protein of this virus gets attached with the ACE2 receptors present on human cells. […] The new virus is fast spreading, but it utilizes the same RBD and ACE2 receptors along with furin present in human cells.
32974340 SARS-CoV-2 binding receptor ACE2 and the S protein priming protease TMPRSS2 are co-expressed by a subset of syncytiotrophoblasts (STB) in the first trimester and extravillous trophoblasts (EVT) in the second trimester human placenta. […] Additionally, the term placenta of multiple species including humans expressed ACE2, DPP4, and ANPEP along with the viral S protein proteases. […] The ACE2- and TMPRSS2-positive (ACE2 + TMPRSS2 +) placental subsets expressed mRNA for proteins involved in viral budding and replication. […] Further, we discovered unique signatures of genes in ACE2 + TMPRSS2 + STBs and EVTs. […] The ACE2 + TMPRSS2 + STBs are highly differentiated cells and express genes involving mitochondrial metabolism and glucose transport. […] The second trimester ACE2 + TMPRSS2 + EVTs are enriched for markers of endovascular trophoblasts.
32974373 It has been reported that angiotensin-converting enzyme 2 (ACE2) is one of the major cellular entry receptors of SARS-CoV-2; thus, high ACE2 expression may increase susceptibility to infection. […] Therefore, we analyzed the expression of ACE2 in the blood to identify the individuals who may be susceptible to infection. […] Methods: In total, 229 subjects were enrolled in this study, and reverse transcription-quantitative polymerase chain reaction and ELISA assay was used to identify the level of ACE2 mRNA expression and ACE2 protein level in the blood. […] Independent Student’s t-test, Pearson’s linear correlation, logistic regression analysis, and multiple linear regression correlation were performed to assess the association between these factors and the expression of ACE2. […] Results: Higher level of ACE2 was observed in females, older subjects, subjects with hypertension, subjects with a cardiocerebrovascular disease, male smokers, and subjects with cancer (p < 0.05) than in other subjects. […] Multiple linear regression analysis showed that there is a statistically significant correlation between being a female and ACE2 expression (β = 0.550, p < 0.001), between older age and ACE2 expression (β = 0.197, p = 0.003), between smoking and ACE2 expression (β = 0.163, p = 0.037), and between cancer and ACE2 expression (β = 0.265, p < 0.001). […] Logistic regression analysis revealed that female subjects (odds ratio [OR] = 2.255, 95% confidence interval [CI] = 1.770-2.872), subjects with hypertension (OR = 1.264, 95% CI = 1.075-1.486), subjects with a cardiocerebrovascular disease (OR = 1.271, 95% CI = 1.023-1.579), subjects with cancer (OR = 1.695, 95% CI = 1.253-2.293), and subjects above 60 years of age (OR = 3.097, 95% CI = 1.078-8.896) are at an increased risk of infection due to their high expression of ACE2. […] Conclusion: The level of ACE2 is higher in females, older subjects, smokers, and subjects with cancer than in other subjects, indicating that some of which are at higher risk for the severe forms of COVID-19 when they are exposed to the SARS-Cov-2.
32975064 The cellular entry of severe respiratory syndrome coronavirus-2 (SARS-CoV-2) is mediated by interaction with the human angiotensin-converting enzyme 2 (ACE2), a receptor that is expressed on both lung and intestinal epithelial cells. […] ACE2 expression was low and remained unaltered in the gut of patients with ulcerative colitis (UC), Crohn’s disease (CD), intestinal Behćet’s disease (BD), and intestinal tuberculosis (TB), when compared with that of healthy individuals.
32975865 Angiotensin-converting enzyme 2 (ACE2) is identified as a key cell entry receptor for SARS-CoV-2 and suggested to be a limiting factor for viral entry at the initial infection stage. […] Recent studies have demonstrated that ACE2 expression is highly enriched in nasal epithelial cells and type II alveolar epithelial cells, highlighting the importance of respiratory tract as the primary target site of SARS-CoV-2. […] The expression of ACE2 in airway epithelial cells is tightly regulated by inflammatory milieu and environmental and internal stimuli. […] Very recently, ACE2 has been reported to have different expression levels in airways under distinct chronic inflammatory airway diseases, such as chronic obstructive pulmonary disease (COPD) and allergic asthma, which may associate with the COVID-19 risk and affect the management of primary airway diseases. […] In this review, we focus on the cutting-edge progress in distribution, expression, and regulation of ACE2 in respiratory system in physiological and pathological conditions, and their implication for the development of COVID-19.
32976665 Downregulation of angiotensin converting enzyme 2 (ACE2), a receptor for SARS-CoV-2 and the renin-angiotensin system, as well as inflammatory mechanisms have been suggested to play a role. […] ACE2 is abundant in the gut and associated with gut microbiota composition.
32977101 We speculate that SARS-CoV-2 could have caused angiotensin-converting enzyme-2 (ACE2) receptor internalization in the nucleus of the solitary tract and other midbrain nuclei, impairing baroreflex and chemoreceptor response, and inhibiting the compensatory tachycardia during acute hypocapnic hypoxemia.
32979436 The SARS-CoV-2 spike glycoproteins (SGPs) and human angiotensin converting enzyme 2 (ACE2) are the two key targets for the prevention and treatment of COVID-19. […] In the current study, a series of polysaccharides from Saccharina japonica were prepared to investigate the structure-activity relationship on the binding abilities of polysaccharides (oligosaccharides) to pseudotype particles, including SARS-CoV-2 SGPs, and ACE2 using surface plasmon resonance. […] Sulfated galactofucan (SJ-D-S-H) and glucuronomannan (Gn) displayed strongly inhibited interaction between SARS-CoV-2 SGPs and heparin while showing negligible inhibition of the interaction between SARS-CoV-2 SGPs and ACE2.
32979476 These targets including an important host cell receptor, i.e., angiotensin-converting enzyme ACE2 and several viral proteins e.g. spike glycoprotein (S) containing S1 and S2 domains, SARS CoV Chymotrypsin-like cysteine protease (3CLpro), papain-like cysteine protease (PLpro), helicases and RNA-dependent RNA polymerase (RdRp).
32980345 A striking expression of ACE2 on the small bowel enterocyte brush border supports intestinal infectivity by SARS-CoV-2. […] Commonly used IBD medications, both biologic and non-biologic, do not significantly impact ACE2 and TMPRSS2 receptor expression in the uninflamed intestines.
32980434 Of note, ACE2 is responsible for the host cell entry of the virus.
32981023 The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could interact with angiotensin-converting enzyme 2 (ACE2) in the endothelial, neural, and glial cells. […] In the present study, we reviewed the most common neurological manifestations and complications that emerged after infection with the SARS-CoV-2 and discussed their possible relation to the expression and function of ACE2.
32981365 ACE2 (angiotensin-converting enzyme 2) is a key component of the renin-angiotensin-aldosterone system. […] Yet, little is known about the clinical and biologic correlates of circulating ACE2 levels in humans. […] We assessed the clinical and proteomic correlates of plasma (soluble) ACE2 protein levels in human heart failure. […] We measured plasma ACE2 using a modified aptamer assay among PHFS (Penn Heart Failure Study) participants (n=2248). […] We performed an association study of ACE2 against ≈5000 other plasma proteins measured with the SomaScan platform. […] Plasma ACE2 was not associated with ACE inhibitor and angiotensin-receptor blocker use. […] Plasma ACE2 was associated with older age, male sex, diabetes mellitus, a lower estimated glomerular filtration rate, worse New York Heart Association class, a history of coronary artery bypass surgery, and higher pro-BNP (pro-B-type natriuretic peptide) levels. […] Plasma ACE2 exhibited associations with 1011 other plasma proteins. […] In pathway overrepresentation analyses, top canonical pathways associated with plasma ACE2 included clathrin-mediated endocytosis signaling, actin cytoskeleton signaling, mechanisms of viral exit from host cells, EIF2 (eukaryotic initiation factor 2) signaling, and the protein ubiquitination pathway. […] In conclusion, in humans with heart failure, plasma ACE2 is associated with various clinical factors known to be associated with severe coronavirus disease 2019 (COVID-19), including older age, male sex, and diabetes mellitus, but is not associated with ACE inhibitor and angiotensin-receptor blocker use. […] Plasma ACE2 protein levels are prominently associated with multiple cellular pathways involved in cellular endocytosis, exocytosis, and intracellular protein trafficking. […] Whether these have a causal relationship with ACE2 or are relevant to novel coronavirus-2 infection remains to be assessed in future studies.
32981369 The virus responsible for COVID-19-severe acute respiratory syndrome coronavirus 2-gains entry into host cells via ACE2 (angiotensin-converting enzyme 2). […] ACE2 is a primary enzyme within the key counter-regulatory pathway of the renin-angiotensin system (RAS), which acts to oppose the actions of Ang (angiotensin) II by generating Ang-(1-7) to reduce inflammation and fibrosis and mitigate end organ damage. […] In addition, recognition of the role of ACE2 and the RAS in COVID-19 has renewed interest in its role in the pathophysiology of cardiovascular disease in general. […] We discuss sound methodological approaches to quantifying enzyme content and activity (ACE, ACE2), peptides (Ang II, Ang-[1-7]), and receptors (types 1 and 2 Ang II receptors, Mas receptor).
32981925 Expressions of BNP, CXCL1, CXCL2, IL-6, IL-8 and TNF-α were upregulated, while ACE2 was downregulated.
32982720 So far COVID-19 therapies have targeted various pathogenic mechanisms, namely the neutralization of ACE2 receptors or SARS-CoV-2 spike protein epitopes, the disruption of the endocytic pathways using hydroxychloroquine, arbidol, or anti-Janus kinase inhibitors, the inhibition of RNA-dependent RNA polymerase using nucleotide analogues such as remdesivir, immunosuppressive drugs or molecules acting on the immune response (corticoids, interferons, monoclonal antibodies against inflammatory cytokines, mesenchymal stem cells) and convalescent plasma administration together with numerous drugs with unproven effect against SARS-CoV-2 but with potential antiviral activities (antiretrovirals, antimalarial drugs, antibiotics, etc.).
32983152 SARS-CoV-2 uses the same receptor, angiotensin-converting enzyme 2 (ACE2), as that for SARS-CoV, the coronavirus associated with the SARS outbreak in 2003.
32983259 Genes co-expressed with ACE2 were considered potential therapeutic targets on COVID-19.
32983400 SARS-CoV-2 is a novel highly virulent pathogen which gains entry to human cells by binding with the cell surface receptor - angiotensin converting enzyme (ACE2). […] We computationally contrasted the binding interactions between human ACE2 and coronavirus spike protein receptor binding domain (RBD) of the 2002 epidemic-causing SARS-CoV-1, SARS-CoV-2, and bat coronavirus RaTG13 using the Rosetta energy function. […] We find that the RBD of the spike protein of SARS-CoV-2 is highly optimized to achieve very strong binding with human ACE2 (hACE2) which is consistent with its enhanced infectivity. […] SARS-CoV-2 forms the most stable complex with hACE2 compared to SARS-CoV-1 (23% less stable) or RaTG13 (11% less stable). […] Notably, we calculate that the SARS-CoV-2 RBD lowers the binding strength of angiotensin 2 receptor type I (ATR1) which is the native binding partner of ACE2 by 44.2%. […] By contrasting the spike protein SARS-CoV-2 Rosetta binding energy with ACE2 of different livestock and pet species we find strongest binding with bat ACE2 followed by human, feline, equine, canine and finally chicken. […] These results offer a computational explanation for the increased infection susceptibility by SARS-CoV-2 and allude to therapeutic modalities by identifying and rank-ordering the ACE2 residues involved in binding with the virus.
32984489 Both MERS-CoV and SARS-CoV-2 bind strongly to their cellular receptors, DDP4 and ACE2, respectively, and infect very efficiently both bronchus and lung ex vivo cell cultures which are not protected by a mucus barrier.
32984543 There is clear evidence that, by targeting the angiotensin-converting enzyme II (ACE2) -its natural receptor-, SARS-CoV-2 would mainly affect the renin-angiotensin-aldosterone system (RAAS), whose imbalance triggers diverse symptomatology-associated pathological processes. […] Downstream actors of the RAAS cascade are identified, and their interaction with risk factors and comorbidities are presented, rationalizing why a specific subgroup of individuals that present already lower ACE2 levels is particularly more susceptible to severe forms of disease.
32984768 ACE2, as one of the receptors for SARS-CoV-2 intrusion, is widely distributed in kidney tissues.
32984892 The global COVID-19 pandemic is caused by the SARS-CoV-2 virus entering human cells using angiotensin-converting enzyme 2 (ACE2) as a cell surface receptor. […] ACE2 is shed to the circulation, and a higher plasma level of soluble ACE2 (sACE2) might reflect a higher cellular expression of ACE2. […] The present study explored the associations between sACE2 and clinical factors, cardiovascular biomarkers, and genetic variability. […] The sACE2 protein level was measured by the Olink Proteomics® Multiplex CVD II96 × 96 panel. […] Higher levels of sACE2 were statistically significantly associated with male sex, cardiovascular disease, diabetes, and older age. […] The sACE2 level was most strongly associated with the levels of GDF-15, NT-proBNP, and hs-cTnT. […] When adjusting for these biomarkers, only male sex remained associated with sACE2. […] We found no statistically significant genetic regulation of the sACE2 level. […] Male sex and clinical or biomarker indicators of biological ageing, cardiovascular disease, and diabetes are associated with higher sACE2 levels. […] The levels of GDF-15 and NT-proBNP, which are associated both with the sACE2 level and a higher risk for mortality and cardiovascular disease, might contribute to better identification of risk for severe COVID-19 infection.
32985199 SARS-CoV-2 has been shown to use the SARS-CoV receptor ACE2 for entry and serine protease TMPRSS2 for S protein.
32985211 Resveratrol was shown to mitigate the major pathways involved in the pathogenesis of SARS-CoV-2, including regulation of the renin-angiotensin system (RAS) and expression of angiotensin-converting enzyme 2 (ACE2), stimulation of immune system and downregulation of pro-inflammatory cytokines release. […] Keywords: SARS-CoV-2; Resveratrol; antiviral activity; immune response; ACE2; oxidative stress; HbF.
32985513 To facilitate the development of medical approaches and novel treatments, we compared the ACE2 receptor, and TMPRSS2 and Furin proteases usage of the SARS-CoV-2 Spike glycoprotein in human and in a panel of animal models, i.e. guinea pig, dog, cat, rat, rabbit, ferret, mouse, hamster and macaque. […] Here we showed that ACE2, but not TMPRSS2 or Furin, has a higher level of sequence variability in the Spike protein interaction surface, which greatly influences Spike protein binding mode. […] Using molecular docking simulations we compared the SARS-CoV and SARS-CoV-2 Spike proteins in complex with the ACE2 receptor and showed that the SARS-CoV-2 Spike glycoprotein is compatible to bind the human ACE2 with high specificity. […] Computational analysis of binding modes and protein contacts indicates that macaque, ferrets and hamster are the most suitable models for the study of inhibitory antibodies and small molecules targeting the SARS-CoV-2 Spike protein interaction with ACE2. […] Since TMPRSS2 and Furin are similar across species, our data also suggest that transgenic animal models expressing human ACE2, such as the hACE2 transgenic mouse, are also likely to be useful models for studies investigating viral entry.
32986928 Angiotensin-converting enzyme 2 (ACE2) appears to be the key functional receptor for the virus.
32987060 The factors such as directly pathogen-mediated damage to cardiomyocytes, down-regulated angiotensin-converting enzyme 2 (ACE2) expression, excessive inflammatory response, hypoxia and adverse drug reaction, are closely related to the occurrence and development of the course of COVID-19.
32989429 SARS-CoV-2 cases had higher ACE2, but lower TMPRSS2, BSG/CD147, and CTSB expression compared with negative cases. […] COVID-19 patients’ age negatively affected ACE2 expression. […] Principal-component analysis determined that ACE2, MX1, MX2, and BSG/CD147 expression was able to cluster non-COVID-19 and COVID-19 individuals. […] Altogether, these findings support differences in ACE2, MX1, MX2, and BSG/CD147 expression between COVID-19 and non-COVID-19 patients and point out to MX1 as a critical responder in SARS-CoV-2 infection.
32990314 The discovery of its homologue, ACE2, 20 years ago has led to intensive comparisons of these two enzymes revealing surprising structural, catalytic and functional distinctions between them. […] ACE2 plays multiple roles not only as a vasopeptidase but also as a regulator of amino acid transport and serendipitously as a viral receptor, mediating the cellular entry of the coronaviruses causing severe acute respiratory syndrome (SARS) and, very recently, COVID-19. […] Catalytically, ACE2 functions as a monocarboxypeptidase principally converting the vasoconstrictor angiotensin II to the vasodilatory peptide Ang-(1-7) thereby counterbalancing the action of ACE on the renin-angiotensin system (RAS) and providing a cardioprotective role. […] Unlike ACE, ACE2 does not metabolise bradykinin nor is it inhibited by classical ACE inhibitors. […] Interest in ACE2 biology and its potential as a possible therapeutic target has surged in recent months as the COVID-19 pandemic rages worldwide. […] This review highlights the surprising discoveries of ACE2 biology during the last 20 years, its distinctions from classical ACE and the therapeutic opportunities arising from its multiple biological roles.
32990980 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) gains access to host cells by attaching to angiotensin-converting enzyme 2 (ACE2). […] Vitamin D (VitD) can upregulate ACE2 and has an antagonistic effect on Renin, which exerts a vasodilatation and anti-inflammatory effect against coronavirus disease (COVID-19). […] However, it may also facilitate viral entry by increasing ACE2 as the main SARS-CoV-2 receptor and mediates ROS production through NADPH oxidase, as a double-edged sword effect.
32991251 This population has up-regulation of the angiotensin converting enzyme-2 (ACE2) receptor, which is exploited by COVID-19 as the route of entry and infection. […] Viral envelope proteins bind to and degrade ACE2 receptors, thus preventing normal ACE2 function. […] COVID-19 infection causes imbalances in ACE2 and induces an inflammatory immune response, known as a cytokine storm, both of which amplify comorbidities within the host.
32991738 Angiotensin-converting enzyme 2 (ACE2) has been identified as the functional receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and a target for disease prevention. […] However, the relationship between ACE2 expression and its clinical implications in SARS-CoV-2 pathogenesis remain unknown. […] Here, we explored the location and expression of ACE2, and its correlation with gender, age and cigarette smoke (CS), in a CS-exposed mouse model and 224 non-malignant lung tissues (125 non-smokers, 81 current smokers and 18 ex-smokers) by immunohistochemistry. […] Moreover, the correlations of ACE2 with CS-induced oxidative stress-related markers, hypoxia inducible factor-1α (HIF-1α), inducible nitric oxide synthase (iNOS), and 4-hydroxynonenal (4-HNE) were investigated. […] Chromatin immunoprecipitation and luciferase reporter assays identified the cause of ACE2 overexpression in human primary lung epithelial cells. […] We demonstrated that ACE2 was predominantly overexpressed on the apical surface of bronchial epithelium, while reduced in alveolar epithelium, owing to the dramatically decreased abundance of alveolar type II pneumocytes in CS-exposed mouse lungs. […] Consistent with this, ACE2 was primarily significantly overexpressed in human bronchial and alveolar epithelial cells in smokers regardless of age or gender. […] Decreased ACE2 expression was observed in bronchial epithelial cells from ex-smokers compared with current-smokers, especially in those who had ceased smoking for more than 10 years. […] Moreover, ACE2 expression was positively correlated with the levels of HIF-1α, iNOS, and 4-HNE in both mouse and human bronchioles. […] Finally, our results showed that HIF-1α transcriptionally upregulates ACE2 expression. […] Our results indicate that smoking-induced ACE2 overexpression in the apical surface of bronchial epithelial cells provide a route by which SARS-CoV-2 enters host cells, which supports clinical relevance in attenuating the potential transmission risk of COVID-19 in smoking populations by smoking cessation.
32991842 Here we show that D614G was more infectious than the ancestral form on human lung cells, colon cells, and on cells rendered permissive by ectopic expression of human ACE2 or of ACE2 orthologs from various mammals, including Chinese rufous horseshoe bat and Malayan pangolin. […] D614G did not alter S protein synthesis, processing, or incorporation into SARS-CoV-2 particles, but D614G affinity for ACE2 was reduced due to a faster dissociation rate. […] Assessment of the S protein trimer by cryo-electron microscopy showed that D614G disrupts an interprotomer contact and that the conformation is shifted toward an ACE2 binding-competent state, which is modeled to be on pathway for virion membrane fusion with target cells.
32992409 The new coronavirus uses membrane-bound angiotensin-converting enzyme 2 (ACE2) to enter into the cells, such as SARS-CoV, and mostly affects the respiratory tract. […] SIGNIFICANCE OF THE STUDY: This review summarized current information on COVID-19 (epidemiology, pathophysiology, clinical, laboratory, cardiovascular diseases, ACE2 and pharmacological agents) for researchers and reveals guiding data for researchers, especially in the field of cardiovascular system, pharmacology, dysregulation of cellular function in disease, molecular and cell biology and physiology in the regulation of tissue function in health and disease.
32992681 The present study aims to investigate the microRNAs that regulate the expression of hypothalamic angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), essential elements for SARS-CoV-2 cell entry. […] To determine potential hypothalamic miRNAs that can directly bind to ACE2 and TMPRSS2, multiple target bioinformatics prediction algorithms were used, including miRBase, Target scan, and miRWalk2.029. […] Our in silico analysis has revealed that, although there are over 5000 hypothalamic miRNAs, around 31 miRNAs and 29 miRNAs have shown binding sites and strong binding capacity against ACE2 and TMPRSS2, respectively. […] These novel potential hypothalamic miRNAs can be used to identify new therapeutic targets to treat neurological symptoms in COVID-19 patients via regulation of ACE2 and TMPRSS2 expression.
32992731 Proposed mechanisms involve host cell membrane-bound angiotensin-converting enzyme 2 (ACE2), type II transmembrane serine proteases (TTSPs), such as transmembrane serine protease isoform 2 (TMPRSS2), lysosomal endopeptidase Cathepsin L (CTSL), subtilisin-like proprotein peptidase furin (FURIN), and even potentially membrane bound heparan sulfate proteoglycans. […] Here, we show that the expression levels of ACE2, TMPRSS2 and other viral entry-related genes, as well as potential downstream effector genes such as bradykinin receptors, are modulated in the target organs of select disease states. […] In tissues, such as the heart, which normally express ACE2 but minimal TMPRSS2, we found that TMPRSS2 as well as other TTSPs are elevated in individuals with comorbidities compared to healthy individuals.
32993622 Abnormalities in the renin-angiotensin-aldosterone system (RAAS), angiotensin-converting enzyme-2 (ACE2) and the androgen-driven transmembrane serine protease 2 (TMPRSS2) have been elicited as key modulators of SARS-CoV-2.
32993656 We analyzed publicly available RNA microarray datasets for SARS-CoV-2 entry receptors and cofactors ACE2, TMPRSS2, BSG (CD147) and FURIN. […] We found that ACE2 and TMPRSS2 are upregulated in the airways of smokers. […] In asthmatics, ACE2 tended to be downregulated in nasal epithelium, and TMPRSS2 was upregulated in the bronchi.
32994064 Artificial intelligence can have an important role in analysing such data to identify populations at higher risk of COVID-19-related urological pathologies and to suggest treatments that block viral entry into cells by interrupting the angiotensin-converting enzyme 2-transmembrane serine protease 2 (ACE2-TMPRSS2) pathway.
32994673 The virus spike (S) protein finds its binding site, ACE2, widely distributed in all cells and tissues that potentially proffer CoViD-19 pathology. […] Current trends show that variant alleles resulting from single nucleotide polymorphisms (SNPs) of ACE2, and genetic variants of TMPRSS2, with putative distinct affinities for S clip, may determine a complex multi-factorial spectrum of SARS-CoV2 virulence across patients, and predict CoViD-19 susceptibility.
32994678 Results also shows that thrombin binds with SER494 in the spike protein, and GLU37 in the ACE2 receptor.
32995660 Single cell sequencing studies have highlighted the role of cell polarity and the co-expression of proteases, such as Furin, along with ACE2 in the genesis of coronavirus disease rather than exclusively link tissue involvement with ACE2 levels thought previously.
32995920 The last decade was crucial for our understanding of the renin-angiotensin-aldosterone system (RAAS) as a two-axis, counter-regulatory system, divided into the classical axis, formed by angiotensin-converting enzyme (ACE), angiotensin II (Ang II), and the angiotensin type 1 receptor (AT1R), and the alternative axis comprising angiotensin-converting enzyme 2 (ACE2), angiotensin-(1-7) (Ang-(1-7)), and the Mas receptor.
32996784 In the current study, using primary isolated human airway smooth muscle (ASM) cells from normal males vs. females as a model, we explored the effect of estrogen vs. testosterone in modulating the expression of angiotensin converting enzyme 2 (ACE2), a cell entry point for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). […] Using confocal imaging, we found that ACE2 is expressed in human ASM. […] Furthermore, Western analysis of ASM cell lysates showed significantly lower ACE2 expression in females compared to males at baseline. […] In addition, ASM cells exposed to estrogen and testosterone for 24 h showed that testosterone significantly upregulates ACE2 expression in both males and females, whereas estrogen downregulates ACE2, albeit not significant compared to vehicle.
32998451 Concerns about the male fertility consequences of SARS-CoV-2 infection have started to emerge, since epidemiologic studies observed that this coronavirus affects male patients more frequently and with increased severity, possibly because of the hormone-regulated expression of angiotensin-converting enzyme 2 (ACE2) receptor. […] A disturbance in fertility is also expected based on studies of the previous SARS-CoV infection, which targets the same ACE2 receptor when entering the host cells. […] In addition, bioinformatics analyses reveal the abundant expression of ACE2 receptor in the male reproductive tissues, particularly in the testis. […] It has been proposed that pharmacological intervention favoring the angiotensin-(1-7)/ACE2/Mas receptor pathway and increasing ACE2 expression and activity could greatly prevent inflammatory lesions in this area.
33001051 The virus enters the respiratory tract cells and other tissues via ACE2 receptors.
33001856 We also suggest that the important gestational shift Th1-Th2 immune response, known as a potential contributor to the severity in cases of viral infections during pregnancy, are counter-regulated by the enhanced-pregnancy-induced ACE2-Ang-(1-7) axis. […] Conversely, we also suggest, that down-regulation of ACE2 receptors induced by SARS-CoV-2 cell entry might have been detrimental in subjects with pre-existing ACE2 deficiency associated with pregnancy.
33002032 The viral infection depends on the attachment of spike (S) glycoprotein to human cell receptor angiotensin-converting enzyme 2 (ACE2). […] The inhibitor consists of two α helical peptides homologues to protease domain (PD) of ACE2. […] Docking studies and molecular dynamic simulation revealed that the inhibitor binds exclusively at the ACE2 binding site of S protein. […] The computed binding affinity of the inhibitor is higher than the ACE2 and thus will likely out compete ACE2 for binding to S protein.
33002515 Capsule summary (33 of 35 words; 2 of 2 sentences): Secukinumab reduced the inflammation and the expression of ACE2, which encodes the SARS-CoV-2 receptor, in plaques of patients with psoriasis. […] Reductions in ACE2 expression with secukinumab significantly correlated with reductions in disease activity.
33003119 In addition, the modulation of endothelial function, the down-regulation of renin, angiotensin-converting-enzyme (ACE) and angiotensin genes and the up-regulation of ACE2 expression is still an area of research.
33003587 The viral entry of SARS-CoV-2 depends on an interaction between the receptor-binding domain of its trimeric spike glycoprotein and the human angiotensin-converting enzyme 2 (ACE2) receptor. […] A better understanding of the spike/ACE2 interaction is still required to design anti-SARS-CoV-2 therapeutics. […] Here, we investigated the degree of cooperativity of ACE2 within both the SARS-CoV-2 and the closely related SARS-CoV-1 membrane-bound S glycoproteins. […] Interestingly, the SARS-CoV-2 spike exhibits a positive cooperativity for monomeric soluble ACE2 binding when compared to the SARS-CoV-1 spike, which might have more structural restraints. […] Our findings can be of importance in the development of therapeutics that block the spike/ACE2 interaction.
33005531 Further investigation revealed differences in immune response regulated by sex hormones, angiotensin-converting enzyme 2 (ACE2) expression, and health behaviours as contributing factors to increased risk of mortality from COVID-19 among males.
33006233 We further report that the gene expression of ACE2, the SARS-CoV-2 receptor, grows in the lung with age, except for subjects on a ventilator.
33006605 The receptor-binding domain (RBD) of SARS-CoV-2 S protein directly interacts with the human angiotensin-converting enzyme 2 (ACE2) on the host cell membrane. […] In addition, we investigated 3705 mutations in SARS-CoV-2 RBD and 11 324 mutations in human ACE2 and found that SARS-CoV-2 neighbor residues G496 and F497 and ACE2 residues D355 and Y41 are critical for the RBD-ACE2 interaction.
33006953 Severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) that causes COVID-19 infections penetrates body cells by binding to angiotensin-converting enzyme-2 (ACE2) receptors. […] Therefore, this mini-review highlights the role of ACE2 receptors in promoting SARS-CoV-2-induced blood-testis/epididymal barrier infiltration and testicular dysfunction.
33007239 This study focuses on host proteases that proteolytically activate the SARS-CoV-2 spike protein, critical for its fusion after binding to angiotensin-converting enzyme 2 (ACE2), as antiviral targets.
33008593 We determined the expression levels of receptor ACE2 and CD147, and serine protease TMPRSS2 in human and mouse brain cell lines and mouse different region of brain tissues with qRT-PCR and Western blot. […] ACE2 is lower but CD147 is higher expressed in mostly brain cell lines and mouse brain tissues comparing with lung cell line and tissue, and TMPRSS2 has consistent expression in brain cell lines and mouse lung tissues.
33009240 The potential pathophysiology for SARS-CoV-2 to affect the target is via the receptor, angiotensin-converting enzyme 2 (ACE2). […] ACE2 can be found in the respiratory, cardiovascular, gastrointestinal tract, urinary tract, and reproductive organs such as human ovaries and Leydig cells in the testis.
33010584 The virus enters the nervous system either directly through nerve pathways or indirectly through the ACE2 receptor.
33011745 Here, we determined the expression of the SARS-CoV2 receptor, angiotensin converting enzyme 2 (ACE2) and its associated cellular serine protease TPMRSS2 in the dental pulp under normal and inflamed conditions. […] Using existing datasets we show that both ACE2 and TPMRSS2 are expressed in the dental pulp and, that their expression does not change under conditions of inflammation.
33013059 COVID-19 enters the respiratory tract through the ACE2 receptor on alveoli through binding of s-protein of the virus and causes injuries though the cytopathic effect, as well as cytokines and other mediators, released after developing sepsis.
33013062 It enters the respiratory tract through angiotensin converting enzyme-2 (ACE2) receptors on alveoli.
33013423 Lung immunoblot analysis of smokers, COPD and IPF subjects revealed increased abundance of proteases and receptor/spike protein like TMPRSS2, furin, and DPP4 in association with a slight increase in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor ACE2 levels. […] Overall, these findings suggest that altered transcription of target genes that regulate mitochondrial function, cellular senescence, and telomere attrition in the pathobiology of lung aging in COPD and IPF is associated with alterations in SARS-CoV-2 ACE2-TMPRSS2-Furin-DPP4 axis as pharmacological targets for COVID-19.
33014653 The novel coronavirus disease of 2019 (COVID-19) is caused by the binding of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to angiotensin-converting enzyme 2 (ACE2) receptors present on various locations such as the pulmonary alveolar epithelium and vascular endothelium.
33015411 One of the hotspots of pharmacological interventions is to inhibit binding of virus with the host cells, which is mediated by Spike glycoprotein of SARS-CoV-2 and ACE2 receptors present on the human cells.
33015820 ACE2 long served as the human gateway for multiple coronaviruses, including the currently pandemic SARS-CoV-2. […] This mini-review explores the potential of targeting ACE2 in blocking viral penetrance. […] PubMed search was conducted using the terms: “coronaviridae”, “peptidyl-dipeptidase A”, “ACE2”, “SARS”, and “SARS-CoV-2”. […] Four main methods of blocking ACE2-mediated viral penetrance were identified: receptor blockage, receptor decoying, receptor shedding, and co-receptor inhibition. […] Drugs that inhibit viral binding to ACE2 present a strong choice for the current, and if necessary, future outbreaks.
33015868 SARS-CoV-2 spike protein binding to angiotensin-converting enzyme 2 (ACE2) is critical for viral cell entry and infection. […] Here we integrate species differences in susceptibility with multiple in-depth structural analyses to identify key ACE2 amino acid positions including 30, 83, 90, 322, and 354 that distinguish susceptible from resistant species. […] We also demonstrate that SARS-CoV-2 is nearly optimal for binding ACE2 of humans compared to other animals, which may underlie the highly contagious transmissibility of this virus among humans. […] Taken together, our findings define potential ACE2 and SARS-CoV-2 residues for therapeutic targeting and identification of animal species on which to focus research and protection measures for environmental and public health.
33017071 Angiotensin-converting enzyme 2 (ACE2) has been identified as necessary cell entry point for SARS-CoV-2. […] Previous animal studies have demonstrated an increased ACE2 expression following treatment with either angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB) that have led to a massive precariousness regarding the optimal cardiovascular therapy during this pandemic. […] We have measured ACE2 mRNA expression using real-time quantitative polymerase chain reaction in atrial biopsies of 81 patients undergoing coronary artery bypass grafting and we compared 62 patients that received ACEi/ARB vs. 19 patients that were not ACEi/ARB-treated. […] We found atrial ACE2 mRNA expression to be significantly increased in patients treated with an ACEi or an ARB, independent of potential confounding comorbidities. […] Interestingly, the cardiac ACE2 mRNA expression correlated significantly with the expression in white blood cells of 22 patients encouraging further evaluation if the latter may be used as a surrogate for the former. […] Similarly, analysis of 18 ventricular biopsies revealed a significant and independent increase in ACE2 mRNA expression in patients with end-stage heart failure that were treated with ACEi/ARB. […] On the other hand, cardiac unloading with a left ventricular assist device significantly reduced ventricular ACE2 mRNA expression. […] Treatment with ACEi/ARB is independently associated with an increased myocardial ACE2 mRNA expression in patients with coronary artery disease and in patients with end-stage heart failure. […] Nevertheless, haemodynamic factors seem to be equally important for regulation of cardiac ACE2 mRNA expression.
33017906 The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein mediates viral cellular entry via the ACE2 receptor.
33017910 The receptor for corona virus and influenza A is the mucosal cell membrane protein angiotensin converting enzyme 2 (ACE2), which is abundant on the membrane of alveolar cells and enterocytes. […] It has an affinity of 39.3 nM to ACE2, much higher than that of the corona S1. […] The issues to be investigated are the affinity of HDEF5 to S1 protein, the ability of recombinant HDEF5 function in attaching both ACE2 and S1, and the feasibility to perform aerosol spray of this protein.
33017914 ALA reduces ADAM17 activity and ACE2 upregulation.
33020502 To enter host cells, the viral spike protein (S-protein) binds to its receptor, ACE2, and is then processed by TMPRSS2. […] Whilst receptor binding contributes to the viral host range, S-protein:ACE2 complexes from other animals have not been investigated widely. […] To predict infection risks, we modelled S-protein:ACE2 complexes from 215 vertebrate species, calculated changes in the energy of the complex caused by mutations in each species, relative to human ACE2, and correlated these changes with COVID-19 infection data. […] We predict that mutations are more detrimental in ACE2 than TMPRSS2.
33020722 Here, we screened 26 animal counterparts of the human ACE2 (hACE2), the receptor for SARS-CoV-2 and SARS-CoV, and found that the ACE2s from various species, including pets, domestic animals and multiple wild animals, could bind to SARS-CoV-2 receptor binding domain (RBD) and facilitate the transduction of SARS-CoV-2 pseudovirus. […] We further resolved the cryo-electron microscopy (cryo-EM) structure of the cat ACE2 (cACE2) in complex with the SARS-CoV-2 RBD at a resolution of 3 Å, revealing similar binding mode as hACE2 to the SARS-CoV-2 RBD.
33022818 The SARS-CoV-2-induced kidney damage is expected to be multifactorial; directly it can infect the kidney podocytes and proximal tubular cells and based on an angiotensin-converting enzyme 2 (ACE2) pathway it can lead to acute tubular necrosis, protein leakage in Bowman’s capsule, collapsing glomerulopathy and mitochondrial impairment.
33023417 The pathogenesis of the disease is triggered by the entry of SARS-CoV-2 via its spike protein into ACE2-bearing host cells, particularly pneumocytes, resulting in overactivation of the immune system, which attacks the infected cells and damages the lung tissue. […] The interaction of the SARS-CoV-2 receptor binding domain (RBD) with host cells is primarily mediated by the N-terminal helix of ACE2; thus, inhibition of the spike-ACE2 interaction may be a promising therapeutic strategy for blocking the virus entry into host cells. […] In this paper, we used an in-silico approach to explore small-molecule α-helix mimetics as inhibitors that may disrupt the attachment of SARS-CoV-2 to ACE2. […] First, the RBD-ACE2 interface in the 6M0J structure was studied by the MM-GBSA decomposition module of the HawkDock server, which led to the identification of two critical target regions in the RBD.
33024003 Increased expression of pulmonary ACE2, the SARS-CoV-2 receptor, could contribute to increased infectivity of COVID-19 in subjects with diabetes, but ACE2 expression has not been studied in lung tissue of subjects with diabetes. […] We therefore studied ACE2 mRNA and protein expression in lung tissue samples of patients with and without diabetes that were collected between 2002 and 2020 from patients undergoing lobectomy for lung tumors. […] For immunohistochemical staining, samples from 26 subjects with diabetes were compared to 66 randomly chosen control samples. mRNA expression of ACE2 was measured by quantitative RT-PCR. […] Protein levels of ACE2 were visualized by immunohistochemistry on paraffin-embedded lung tissue samples and quantified in alveolar and bronchial epithelium. […] Pulmonary ACE2 mRNA expression was not different between subjects with or without diabetes. […] In contrast, protein levels of ACE2 were significantly increased in both alveolar tissue and bronchial epithelium of patients with diabetes as compared with control subjects, independent of smoking, COPD, BMI, RAAS-inhibitor use and other potential confounders. […] To conclude, we show increased bronchial and alveolar ACE2 protein expression in patients with diabetes. […] Further research is needed to elucidate whether up-regulation of ACE2 expression in airways and lungs has consequences on infectivity and clinical outcomes of COVID-19.
33024017 The nanodecoy, made by fusing cellular membrane nanovesicles derived from human monocytes and genetically engineered cells stably expressing angiotensin converting enzyme II (ACE2) receptors, possesses an antigenic exterior the same as source cells.
33024851 We collect the nasopharyngeal and oropharyngeal swabs of 63 subjects with severe symptoms or contacts with COVID-19 confirmed cases to perform a pilot-study aimed to verify the “in situ” expression of SARS-CoV-2 host invasion genes (ACE2, TMPRSS2, PCSK3, EMILIN1, EMILIN2, MMRN1, MMRN2, DPP4). […] ACE2 (FC = +1.88, p ≤ 0.05) and DPP4 (FC = +3, p < 0.01) genes showed a significant overexpression in COVID-19 patients. […] ACE2 and DPP4 expression levels had a good performance (AUC = 0.75; p < 0.001) in distinguishing COVID-19 patients from negative subjects. […] Interestingly, we found a significant positive association of ACE2 mRNA and PCSK3, EMILIN1, MMRN1 and MMRN2 expression and of DPP4 mRNA and EMILIN2 expression only in COVID-19 patients. […] Noteworthy, a subgroup of severe COVID-19 (n = 7) patients, showed significant high level of ACE2 mRNA and another subgroup of less severe COVID-19 patients (n = 6) significant raised DPP4 levels. […] These results indicate that a group of SARS-CoV-2 host invasion genes are functionally related in COVID-19 patients and suggests that ACE2 and DPP4 expression level could act as genomic biomarkers.
33025029 In this paper, we describe the characteristics of SARS-CoV‑2 and its functional receptor angiotensin-converting enzyme 2 (ACE2). […] Furthermore, we explore the impact of virus-induced myocardial damage, decreased ACE2 activity, immune imbalance, hypoxemia, and heart damage caused by antiviral drugs.
33025046 This is due to a decrease in Angiotensin-converting enzyme 2 (ACE2) gene expression in the nose and bronchial cells of allergic airway diseases.
33025652 Some antihypertensive drugs affect ACE2 expression or activity (ACE inhibitors and angiotensin II receptor blockers [ARBs]), suggesting use of other hypertensives might be preferable, such as calcium channel blockers (CCBs). […] Varying effects of different classes of antihypertensives on immune and inflammatory markers do not suggest antihypertensive use based on their role in ACE2 expression, but instead suggest investigation of the role of antihypertensives in immune function and inflammation might reveal important information that could optimize their use in SARSCoV-2.
33026669 Infection of coronavirus in diabetic patients may trigger acute hyperglycemia due to increased secretion of hyperglycemic hormones, extensive application of glucocorticoids to patients with severe symptoms and the potential pathogenicity of coronavirus in pancreas expressing angiotensin-converting enzyme 2 (ACE2) This article is protected by copyright.
33026922 Recent studies have revealed that both SARS CoV and SARS-CoV-2 invade target cells through a membrane-bound angiotensin-convert enzyme 2 (ACE2), an important component of the renin-angiotensin system (RAS) which maintains human homeostasis, whereas MERS utilizes host cells’ receptor dipeptidyl peptidase 4 (DPP4) for entry.
33027617 These two classes of IGHV3-53 antibodies both target the ACE2 receptor binding site, but with very different angles of approach and molecular interactions.
33029105 The novel coronavirus gains entry into humans by targeting the ACE2 receptor that found on lung cells, which destroy human lungs through cytokine storms, and this leads to hyperinflammation, forcing the immune cells to destroy healthy cells.
33029419 ACE2: Angiotensin-converting enzyme 2; COVID-19: coronavirus disease 2019; CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; HIV: human immunodeficiency virus; IRB, Institutional Review Board; ISH, in situ hybridisation; RT-PCR: reverse transcriptase-PCR; SARS-CoV-2, severe acute respiratory syndrome coronavirus-2; TMPRSS2: transmembrane protease, serine 2; WBC: white blood cell.
33029570 Entry of SARS-CoV-2, etiological agent of COVID-19, in the host cell is driven by the interaction of its spike protein with human ACE2 receptor and a serine protease, TMPRSS2. […] Although complex between SARS-CoV-2 spike protein and ACE2 has been structurally resolved, the molecular details of the SARS-CoV-2 and TMPRSS2 complex are still elusive.
33029696 This single-stranded RNA virus uses Angiotensin-converting enzyme 2 (ACE2) as a receptor for entry into the host cell. […] Overexpression of ACE2 is mainly observed in hypertensive, diabetic and heart patients that make them prone to SARS-CoV-2 infection.
33029758 The S spike protein of SARS-CoV-2 binds with angiotensin-converting enzyme 2 (ACE2) as a functional “receptor” and then enters into host cells to replicate and damage host cells and organs. […] ACE2 plays a pivotal role in the inflammation, and its downregulation may aggravate COVID-19 via the renin-angiotensin system, including by promoting pathological changes in lung injury and involving inflammatory responses. […] This review summarizes the current evidence and understanding of the underlying mechanisms of SARS-CoV-2, ACE2 and inflammation co-mediated multi-organ injury or failure in COVID-19 patients.
33029768 SARS-CoV-2 interacts with Renin angiotensin system by utilizing angiotensin-converting enzyme 2 (ACE2) as a receptor for its cellular entry. […] This interaction hampers the protective action of ACE2 in the cells and causes injuries to organs due to persistent angiotensin II (Ang-II) level.
33030073 According to the obtained evidence, Vitamin D (VitD) enhances the ACE2/Ang(1-7)/MasR pathway activity, and it also reduces cytokine storms and the ARS risk. […] In the present review, we have explained the effects of VitD on the renin-angiotensin system (RAS) function and angiotensin-converting enzyme2 (ACE2) expression.
33031368 There is evidence indicating that these drugs upregulate ACE2, a key component of the renin-angiotensin system (RAS) and is found on the cells of a number of tissues, including the epithelial cells in the lungs. […] While ACE2 has a beneficial role in many diseases such as hypertension, diabetes, and cardiovascular disease, it also serves as a receptor for both SARS-CoV and SARS-CoV-2 via binding with the spike protein of the virus, thereby allowing it entry into host cells. […] To that end, we have developed a mathematical model that represents the RAS, binding of ACE2 with SARS-CoV-2 and the subsequent cell entry, and the host’s acute inflammatory response. […] Model simulations indicate that whether the extent of tissue damage may be exacerbated by ACEi or ARB treatment depends on a number of factors, including the level of existing inflammation, dosage, and the effect of the drugs on ACE2 protein abundance.
33031602 The virus is believed to be evolved in a recombined form of bat and animal coronavirus with the capacity to infect human host using the ACE2 receptors as an entry point. […] In the present review, we have discussed the significance of age and sex-dependent pattern of ACE2 receptor expression and ACE2 variants in the immune protective mechanism of the disease virulence. […] We have also added a brief note on the importance of sex hormones in the pathogenesis of ACE2 mediated SARS-CoV2 infection.
33031797 According to bulk RNA and single cell RNA sequencing analysis, we found that high expression of both angiotensin converting enzyme 2 (ACE2) and transmembrane Serine Protease 2 (TMPRSS2) makes the lung and intestine vulnerable to SARS-CoV-2.
33032170 Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative pathogen for COVID-19, has been shown to bind to angiotensin converting enzyme 2 (ACE2) protein in human epithelial cells which facilitates its entry in the organ and mediate tissue specific pathogenesis. […] For ACE2 mediated cell entry of the SARS-CoV-2, co-expression of one more protein-Transmembrane protease serine 2 (TMPRSS2) is essential. […] Existing studies suggested significant expression of ACE2 and TMPRSS2 in human vascular endothelium. […] ACE2 has proven role in the maintenance of endothelial integrity inside the vessels. […] Existing in situ evidence for SARS-CoV-1 (the causative agent for SARS pandemic of 2002, which shared ACE2 as cell entry receptor) suggested that virus binding can downregulate ACE2, thus can induce endothelial dysfunction. […] Recently, in situ evidence has been presented that SARS-CoV-2 can infect cells in engineered human vascular endothelium, which can be effectively blocked by using clinical-grade recombinant human ACE2. […] Based on the circumstantial evidence present in the literature, we propose a SARS-CoV-2 cell entry receptor ACE2 based mechanism for vascular thrombosis in COVID-19 patients.
33032965 Notably, SARS-CoV-2, the causative virus of COVID-19, binds to ACE2, which is abundantly present not only in human epithelia of the lung and the small intestine, but also in vascular endothelial cells and arterial smooth muscle cells.
33033170 Angiotensin converting enzyme 2 (ACE2), a crucial factor in COVID-19 pathogenesis, has been identified as a potential target for COVID-19 treatment. […] Smoking and vaping are potential risk factors for COVID-19 which are also shown to upregulate ACE2 expression. […] In this review, we have discussed the pathobiology of COVID-19 in the lungs and brain and the role of ACE2 in the transmission and pathobiology of this disease. […] Further, we have shown possible interactions between nicotine/smoking and ACE2 in the lungs and brain which could aggravate the transmission and pathobiology of COVID-19 resulting in a poor disease outcome. […] It focuses on the potential negative impact of tobacco and nicotine exposure on the outcomes of this disease by interaction with the ACE2 receptor.
33034780 Recently, various studies have shown that angiotensin-converting enzyme 2 (ACE2) acts as the “doorknob” that can be bound by the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which conduces to its entrance to the host cells, and plays an important role in corona virus disease 2019 (COVID-19). […] This paper aims to collect and sorts out the existing drugs, which exert the ability to block the binding of S protein and ACE2 so as to provide directions for the later drug development. […] By reviewing the existing literature, we expound the pathogenesis of SARS-CoV-2 from the perspective of S protein and ACE2 binding, and summarize the drugs and compounds that can interfere with the interaction of spike protein and ACE2 receptor from different ways. […] They can fight SARS-CoV-2 by specifically binding to ACE2 receptor, S protein, or blocking membrane fusion between the host and virus. […] ACE2 is the key point for SARS-CoV-2 to enter the cells, and it is also the focus of drug intervention.
33035337 SARS-CoV-2 uses human angiotensin-converting enzyme 2 (ACE2) for viral entry and transmembrane serine protease family member II (TMPRSS2) for spike protein priming.
33035589 Our review illustrates findings that claim SARS-CoV-2’s arrival onto the ACE2 receptors of neuronal and glial cells mainly via CSF, olfactory nerve, trigeminal nerve, neuronal dissemination, and hematogenous pathways.
33036546 Angiotensin converting enzyme 2 (ACE2) plays a central role in COVID-19 and is a necessary receptor for viral entry into human cells. […] ACE2 normally not only eliminates angiotensin II (Ang II) by converting it to Ang (1-7), but also elicits a beneficial response profile counteracting that of Ang II. […] Molecular analyses of single nuclei from human hearts have shown that ACE2 is most highly expressed by pericytes. […] Furthermore, ACE2 activity is crucial for opposing adverse effects of locally generated Ang II, so virus-mediated internalization of ACE2 could exacerbate pathology by this mechanism. […] While the role of cardiac pericytes in acute heart injury by SARS-CoV-2 requires investigation, expression of ACE2 by these cells has broader implications for cardiac pathophysiology.
33036853 These factors, coupled with imbalance of ACE2 and RAS axis interactions, have been shown to create a prothrombotic environment, favoring thromboembolic events.
33038424 SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) for entry into host cells. […] Since ACE2 is a susceptibility factor for infection, we investigated how diabetic kidney disease and medications alter ACE2 receptor expression in kidneys. […] Single cell RNA profiling of healthy living donor and kidney biopsies from patients with diabetic kidney disease revealed ACE2 expression primarily in proximal tubular epithelial cells. […] ACE2 expression levels were unaltered by exposures to renin angiotensin aldosterone system inhibitors in diabetic kidney disease. […] Bayesian integrative analysis of a large compendium of public-omics datasets identified molecular network modules induced in ACE2-expressing proximal tubular epithelial cells in diabetic kidney disease (searchable at that were linked to viral entry, immune activation, endomembrane reorganization, and RNA processing. […] The diabetic kidney disease ACE2-positive proximal tubular epithelial cell module overlapped with expression patterns seen in SARS-CoV-2 infected cells. […] Similar cellular programs were seen in ACE2-positive proximal tubular epithelial cells obtained from urine samples of 13hospitalized patients with COVID-19, suggesting a consistent ACE2-coregulated proximal tubular epithelial cell expression program that may interact with the SARS-CoV-2 infection processes.
33038909 Studies have shown that protein S interacts with its specific receptor in target cells named as angiotensin-converting enzyme 2 (ACE2).
33039415 In addition, a major component, ACE2, is the entry receptor for SARS-CoV-2.
33039544 Recent studies have reported that similar to SARS-CoV, this strain expresses a spike protein (S) with a receptor binding domain (RBD) that binds to angiotensin-converting enzyme 2 (ACE2) - an enzyme expressed mostly in the endothelium, kidneys, heart, gastrointestinal tract and lungs - to facilitate viral entry and intracellular replication. […] Incidentally, the renin-angiotensin-aldosterone system (RAAS) is integral to physiologic control of both ACE and ACE2 expression, and is an essential system utilized by SARS-CoV-2, albeit with varying schools of thought on how it can affect viral entry. […] We will then discuss the relevance of these interactions on organ-specific ACE2 expression, and provide scientific insights on how this mechanism can potentially affect SARS-CoV-2 infection in the early phases of disease.
33041173 Surface plasmon resonance (SPR) assays and NanoBit assays were used to verify the predicated compounds with their binding activities to spike proteins and inhibitory activities on the SARS-CoV-2 RBD/ACE2 interaction, respectively.
33041407 In this paper, computational approaches were employed, especially the structure-based virtual screening followed by molecular dynamics (MD) simulation as well as binding energy analysis for the computational identification of specific terpenes from the medicinal plants, which can block SARS-CoV-2 S-RBD binding to Human angiotensin-converting enzyme 2 (H-ACE2) and can act as potent anti-COVID-19 drugs after further advancements.
33041626 It has been shown that SARS-CoV-2 uses ACE2 (Angiotensin Converting Enzyme 2) as a cellular receptor for host cell entry through the surface unit of SARS-CoV spike glycoprotein. […] In this brief report, we analyze ACE2 protein expression and localization in human salivary gland, and propose a possible role of saliva in the pathogenesis of Coronavirus disease 2019 (COVID-19).
33042151 The human ACE2 (hACE2) protein is the crucial target for the SARS-CoV’s Spike protein that allows the virus to adhere to host epithelial cells. […] X-ray crystal structures and biophysical properties of protein-protein interactions reveal a large interaction surface with high binding-affinity between SARS-CoV-2 and hACE2 (18 interactions), at least 15-fold stronger than between SARS-CoV-1 and hACE2 (eight interactions). […] Furthermore, interspecies comparisons indicate that ACE2 proteins of man and cat are far closer than dog, ferret, mouse, and rat with significant differences in binding-affinity between Spike and ACE2 proteins. […] The large interaction surface with strong affinity between SARS-CoV-2 and hACE2 (dG-12.4) poses a huge challenge to develop reliable antibody therapy that truly blocks SARS-CoV-2 adherence and infection. […] We gauge that single antibodies against single epitopes might not sufficiently interfere with the strong interaction-synapse between Spike and hACE2 proteins.
33042335 Many reports show that angiotensin converting enzyme II (ACE2) is the cell receptor through which 2019-nCoV enters host cells, and this is similar to the cell entry mechanism of SARS coronavirus. […] Previous studies show that ACE2 is highly expressed in the gastrointestinal tract, especially in the colon. […] In patients with colon cancer, ACE2 expression is significantly increased in tumor tissues compared to tissues from patients with other types of cancer. […] Furthermore, the Database of Gene expression profiling interactive analysis suggests that expression levels for ACE2, TMPRSS2, and AAK1 are positively correlated in colon cells.
33042994 The Renin Angiotensin System (RAS) seems to be involved in COVID-19 natural course, since studies suggest the membrane-bound Angiotensin-converting enzyme 2 (ACE2) works as SARS-CoV-2 cellular receptor. […] This review aims to discuss possible SARS-CoV-2 intracellular signaling pathways, cell entry mechanism and the possible consequences of the interaction with RAS components, including Angiotensin II (Ang II), Angiotensin-(1-7) [Ang-(1-7)], Angiotensin-converting enzyme (ACE), ACE2, Angiotensin II receptor type-1 (AT1), and Mas Receptor. […] Data were obtained independently by the two authors who carried out a search in the PubMed, Embase, LILACS, Cochrane, Scopus, SciELO and the National Institute of Health databases using Medical Subject Heading terms as “SARS-CoV-2,” “COVID-19,” “Renin Angiotensin System,” “ACE2,” “Angiotensin II,” “Angiotensin-(1-7),” and “AT1 receptor.” […] Similarly to other members of Coronaviridae family, the molecular interactions between the pathogen and the membrane-bound ACE2 are based on the cleavage of the spike glycoprotein (S) in two subunits. […] Following the binding of the S1 receptor-binding domain (RBD) to ACE2, transmembrane protease/serine subfamily 2 (TMPRSS2) cleaves the S2 domain to facilitate membrane fusion. […] It is very likely that SARS-CoV-2 cell entry results in downregulation of membrane-bound ACE2, an enzyme that converts Ang II into Ang-(1-7).
33043050 Angiotensin-converting enzyme 2 (ACE2) provides an adhesion site for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. […] The objective of this study was to investigate ACE2 regulation by air pollution during the development of COPD. […] We examined lung injury markers, oxidative stress, inflammation, emphysema, ACE2 and angiotensin II receptor type 1 (AT1) and 2 (AT2) in the lungs after exposure. […] Upregulation of ACE2 was found after 3 months of PM1 exposure; however, ACE2 had decreased by 6 months of PM1 exposure. […] In conclusion, short-term exposure to PM1 increased the ACE2 overexpression in lungs. […] Long-term exposure to PM1 decreased the ACE2 overexpression in emphysema.
33043142 Angiotensin-converting enzyme 2 (ACE2) can mediate coronavirus entry into host cells.
33043253 This work makes an assessment of wildlife susceptibility to SARS-CoV-2 by analyzing the similarities of Angiotensin Converting Enzyme 2 (ACE2) and Transmembrane Protease, Serine 2 (TMPRSS2) -both recognized as receptors and protease for coronavirus spike protein- and the genetic variation of the viral protein spike in the recognition sites. […] Comparisons of aligned sequences were made by selecting amino acids residues of ACE2, TMPRSS2 and S protein; phylogenetic trees were reconstructed using the same sequences.
33043967 Mean serum concentrations of ACE2, angiotensin II, and aldosterone did not differ between the SARS-CoV-2 positive and the control group.
33044654 A subset of patients with acute abdominal pathology were identified with inflammatory pathology in organs with high ACE2 receptor expression including bowel, pancreas, urinary bladder, and kidney. […] Further, COVID-19 positive patients are more likely to have inflammation of organs with high expression of ACE2 receptors than other types of acute abdominal pathology.
33045350 Knowing the ability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to bind to the angiotensin-converting enzyme 2 (ACE2) receptor and to enter cells via endocytosis paved the way for repositioning of old drugs as potential treatment of COVID-19, the disease caused by SARS-CoV-2 infection. […] To conclude, administration of these two drugs using a special drug delivery system provides two kinds of drug targeting: (i) tissue targeting through using an inhaled drug delivery system to achieve high drug concentrations at the respiratory epithelial tissue that overexpress the ACE2 receptor for virus binding; and (ii) cellular targeting of the virus in the acidic vesicles (late endosomes and lysosomes), which represent the fate of endocytic viruses.
33045718 Human neutralizing antibodies (hNAbs) that target the host ACE2 receptor-binding domain (RBD) of the SARS-CoV-2 spike1-5 show therapeutic promise and are being evaluated clincally6-8. […] Structural comparisons allowed classification into categories: (1) VH3-53 hNAbs with short CDRH3s that block ACE2 and bind only to “up” RBDs, (2) ACE2-blocking hNAbs that bind both “up” and “down” RBDs and can contact adjacent RBDs, (3) hNAbs that bind outside the ACE2 site and recognize “up” and “down” RBDs, and (4) Previously-described antibodies that do not block ACE2 and bind only “up” RBDs9.
33046696 Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2, an emerging virus that utilizes host proteins ACE2 and TMPRSS2 as entry factors. […] We identify expression quantitative trait loci for both ACE2 and TMPRSS2, that vary in frequency across world populations. […] We find TMPRSS2 is part of a mucus secretory network, highly upregulated by type 2 (T2) inflammation through the action of interleukin-13, and that the interferon response to respiratory viruses highly upregulates ACE2 expression. […] IL-13 and virus infection mediated effects on ACE2 expression were also observed at the protein level in the airway epithelium. […] Finally, we define airway responses to common coronavirus infections in children, finding that these infections generate host responses similar to other viral species, including upregulation of IL6 and ACE2.
33048778 Here, we examine the structure, replication cycle, phylogeny and genomic organization of this virus and discuss the role of spike (S) protein of the virus, an important structure that interacts with the host ACE2 receptor facilitating viral entry.
33049061 The co-expression network was constructed by mapping the well-known angiotensin converting enzyme (ACE2), TMPRSS2, and host susceptibility genes implicated in COVID-19 genomewide association study (GWAS) onto a cornea, retinal pigment epithelium, and lung. […] We identified a corneal mitochondrial susceptibility module (CMSM) of 14 mitochondrial genes by integrating ACE2 co-expression cluster and SARS-CoV-2 interactome. […] The gene ECSIT, as a cytosolic adaptor protein involved in inflammatory responses, exhibits the strongest correlation with ACE2 in CMSM, which has shown to be an important risk factor for SARS-CoV-2 infection and prognosis.
33049583 Angiotensin converting enzyme 2 (ACE2) receptor can bind to spike protein of SARS-CoV-2. […] Therefore, ACE2 and TMPRSS2 are potential antiviral targets for treatment of prevention of SARS-CoV-2 infection. […] In this study, we discovered that 10-250 μg/mL of GB-2, from Tian Shang Sheng Mu of Chiayi Puzi Peitian Temple, can inhibit ACE2 mRNA expression and ACE2 and TMPRSS2 protein expression in HepG2 and 293 T cells without cytotoxicity. […] GB-2 treatment could decrease ACE2 and TMPRSS2 expression level of lung tissue and kidney tissue without adverse effects, including nephrotoxicity and hepatotoxicity, in animal model. […] In the compositions of GB-2, we discovered that 50 μg/mL of theaflavin could inhibit protein expression of ACE2 and TMPRSS2. […] Theaflavin could inhibit the mRNA expression of ACE2. […] In conclusion, our results suggest that GB-2 and theaflavin could act as potential compounds for ACE2 and TMPRSS2 inhibitors in the further clinical study.
33050463 Moreover, 36 non-synonymous mutations were identified in the receptor-binding domain (RBD) of the spike protein with a low prevalence (<1%) across all genomes, of which only four could potentially enhance the binding of the SARS-CoV-2 spike protein to the human ACE2 receptor.
33051389 A proposed underlying mechanism is that SARS-CoV-2 infects vascular endothelial cells via the angiotensin-converting enzyme 2 (ACE2) and causes inflammation.
33051876 Here, we show that SARS-CoV-2-infected cells express the Spike protein (S) at their surface and fuse with ACE2-positive neighboring cells. […] On the contrary, the TMPRSS2 serine protease, which is known to enhance infectivity of cell-free virions, processes both S and ACE2 and increases syncytia formation by accelerating the fusion process.
33052306 The neuronal nicotinic acetylcholine receptor (nN-AChR) and angiotensin-converting enzyme 2 (ACE2) receptor showed 19.85% sequence identity among themselves. […] However, nicotine showed a higher binding affinity score of -6.33 kcal/mol for the sACE2-INS1 complex than the sACE2 alone with -5.24 kcal/mol. […] A lowered inhibitory constant value of 22.95μM recorded while nicotine interacted with the sACE2-INS1 complex over the sACE2 alone with 151.69 μM. […] In summary, nicotine showed a profound binding affinity for the sACE2-INS1 complex than the sACE2 alone paving for the clinical trials to validate its therapeutic efficacy as a bitter compound against the SARS-CoV-2 virulence.
33052573 The SARS-CoV-2 uses the resembling receptor, angiotensin-converting enzyme 2 (ACE2) as that for SARS-CoV, and mainly feasts through the respiratory tract. […] The ACE2 receptor appearances have been also detected upon glial cells and neurons, which makes them a potential target of SARS-CoV-2 disease (COVID-19). […] Consequently, cells expressing ACE2, apart from lung and cardiovascular tissue, neurons and glial cells may act as targets and are thus vulnerable to SARS-CoV-2 systemic infection as well as its central nervous system (CNS) comorbidities.
33053430 First, using postmortem brain tissue, we show that the angiotensin converting enzyme 2 or ACE2 (a known binding target for the SARS-CoV-2 spike protein), is ubiquitously expressed throughout various vessel calibers in the frontal cortex. […] Moreover, ACE2 expression was upregulated in cases of hypertension and dementia. […] ACE2 was also detectable in primary hBMVECs maintained under cell culture conditions.
33053830 Docking of over 160 aminothiourea derivatives at the SARS-CoV-2 S-protein-human ACE2 receptor interface, whose structure became available recently, has been evaluated for its complex stabilizing potency and subsequently subjected to quantitative structure-activity relationship (QSAR) analysis.
33057007 Angiotensin-converting enzyme 2 (ACE2) has been identified as the host entry receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the COVID-19 pandemic. […] ACE2 is a regulatory enzyme of the renin-angiotensin system and has protective functions in many cardiovascular, pulmonary and metabolic diseases. […] This review summarizes available murine models with systemic or organ-specific deletion of ACE2, or with overexpression of murine or human ACE2. […] The purpose of this review is to provide researchers with the genetic tools available for further understanding of ACE2 biology and for the investigation of ACE2 in the pathogenesis and treatment of COVID-19.
33058755 Crystal structures of two mAbs in complex with the SARS-CoV-2 receptor-binding domain at 2.55 and 2.70 Å revealed a direct block of ACE2 attachment.
33058948 The purpose of this study was to examine the deltoid skin biopsy in twenty-three patients with coronavirus disease 2019 (COVID-19), most severely ill, for vascular complement deposition and correlate this with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA and protein localization and ACE2 expression. […] Microvascular complement deposition strongly colocalized in situ with the SARS-CoV-2 viral proteins including spike glycoproteins in the endothelial cells as well as the viral receptor ACE2 in lesional and nonlesional skin; viral RNA was not evident. […] Microvascular SARS-CoV-2 viral protein, complement, and ACE2 expression was most conspicuous in the subcutaneous fat. […] It is concluded that complement activation is common in grossly normal skin, especially in the subcutaneous fat which may provide a link between severe disease and obesity, in people with severe COVID-19, and the strong colocalization with the ACE2 receptor and viral capsid proteins without viral RNA suggests that circulating viral proteins (ie, pseudovirions) may dock onto the endothelial of these microvessels and induce complement activation.
33059811 To study the expression of angiotensin-converting enzyme 2 (ACE2) and other key molecules of the RAS pathway in normal mice at different developmental stages, and to provide ideas for understanding the infection mechanism of coronavirus disease 2019 (COVID-19) as well as the diagnosis and treatment of children with COVID-19. […] Whole transcriptome resequencing was used to measure the mRNA expression of AGT, ACE, ACE2, Renin, Agtr1a, Agtr1b, Agtr2, and Mas1 in mouse lung tissue. […] The expression of ACE2 in the lungs showed changes from embryonic stage to adult stage. […] At different developmental stages of mice, ACE2 has dynamic expression changes, with high expression in early neonatal and adult mice. […] These suggest that the difference in clinical features between children and adults with COVID-19 might be associated with the different expression levels of ACE2 in the different stages, and further studies are needed for the mechanism.
33061265 We also summarize a possible hypothesis on much less understood and highly debated topics on regard to the etiopathogenesis of ocular involvement in SARS-CoV-2 based on either presence or absence of ACE2 receptor in the ocular surface. […] ACE2 receptors and its expression on the ocular mucosal surface are linked behind the etiopathogenesis of conjunctivitis.
33061805 The virus uses different transmission routes and targets cells and tissues with angiotensin-converting enzyme 2 (ACE2) protein, which makes it contagious.
33061814 Angiotensin-converting enzyme 2 (ACE2) is considered as the most important receptor of SARS-CoV-2 and wildly expressed in human tissues. […] Whereas, the extremely low expression of ACE2 in lung could hardly interpret the severe symptom of pneumonia in COVID-19 patients. […] Consistent with the expression and distribution of ACE2, TMPRSS2 was also highly expressed in digestive, urinary and reproductive systems, but low expressed in lung. […] Our data supposed that fourteen types of tumors might have different susceptibility to the virus according to ACE2, TMPRSS2 and IFITM3 expression patterns.
33062480 This review includes data on the roles of the S protein, ACE2 (angiotensin-converting enzyme 2) receptor, and various human secretory proteases, such as transmembrane protease/serine subfamily member 2 and furin, in the pathogenesis of SARS-CoV-2.
33062950 Highlighted are several sets of small molecules and biologics that act on specific targets, including 3CLpro, PLpro, RdRp, S-protein-ACE2 interaction, helicase/NTPase, TMPRSS2, and furin, which are involved in the viral life cycle or in other aspects of the disease pathophysiology.
33063089 We present preclinical evidence identifying the influence of biological sex on the expression and regulation of angiotensin-converting enzyme 2 (ACE2), which is the main receptor used by SARS-CoV-2 to enter cells. […] However, we note that there is a lack of reports showing that sexual dimorphism of ACE2 expression exists and is of functional relevance in humans.
33063823 The rapid sequencing of the SARS-CoV-2 virus facilitated identification of the receptor for angiotensin converting enzyme 2 (ACE2) as the high affinity binding site that allows virus endocytosis. […] Parallel evidence that coronavirus disease 2019 (COVID-19) disease evolution shows greater lethality in patients with antecedent cardiovascular disease, diabetes, or even obesity questioned the potential unfavorable contribution of angiotensin converting enzyme (ACE) inhibitors or angiotensin II (Ang II) receptor blockers as facilitators of adverse outcomes due to the ability of these therapies to augment the transcription of Ace2 with consequent increase in protein formation and enzymatic activity. […] We review, here, the specific studies that support a role of these agents in altering the expression and activity of ACE2 and underscore that the robustness of the experimental data is associated with weak clinical long-term studies of the existence of a similar regulation of tissue or plasma ACE2 in human subjects.
33064147 Angiotensin-converting enzyme 2 (ACE2) has been highlighted for its role as a receptor for SARS-CoV-2, responsible for the current COVID-19 pandemic. […] This review summarizes current knowledge about ACE2 as a multifunctional protein, focusing on its relevance in inflammatory bowel disease (IBD). […] As an enzyme, ACE2 may be protective in IBD because it favors the counter-regulatory arm of the renin-angiotensin system or deleterious because it metabolizes other anti-inflammatory/repairing elements. […] Meanwhile, as a receptor for SARS-CoV-2, the impact of ACE2 expression/activity on infection is still under debate because no direct evidence has been reported and, again, both protective and deleterious pathways are possible. […] Research has shown that ACE2 regulates the expression of the neutral amino acid transporter B0AT1, controlling tryptophan-associated intestinal inflammation and nutritional status. […] Finally, intact membrane-bound or shed soluble ACE2 can also trigger integrin signaling, modulating the response to anti-integrin biologic drugs used to treat IBD (such as vedolizumab) and fibrosis, a long-term complication of IBD. […] As such, future studies on ACE2 expression/activity in IBD can improve monitoring of the disease and explore an alternative pharmacological target.
33064288 Our critical analysis provides insights into the inflammation cycle induced in the lungs by early virus replication, downregulation and shedding of angiotensin-converting enzyme 2 (ACE2), and in the CS production.
33064690 Such drugs might increase the expression of the fundamental receptor of this new infectious agent: the angiotensin-converting enzyme 2 (ACE2). […] Preclinical observations indicate that the increase of ACE2 expression or the activity by ACEis and ARBs leads to a greater transformation of angiotensin (Ang)-II to Ang-(1-7), which is associated with positive effects on cardiovascular and pulmonary pathophysiology.
33064856 The ACE2 receptor, the binding sites for the COVID-19, is expressed abundantly in the oral cavity, raising the question of whether the mouth is a target for the virus in addition to organs such as kidneys and lungs.
33065601 Data from several preclinical and clinical reports suggest a lower susceptibility for COVID-19 in patients with underlying type 2 airway inflammation including asthma that may be related to a reduced expression of ACE2 and TMPRSS2 receptors for SARS-CoV-2. […] Corticosteroids further decrease expression of the ACE2 and TMPRSS2 receptors, hence may also have a protective effect against infection with SARS-CoV-2. […] Underrepresentation of SARS-CoV-2-infected patients with asthma and related allergic diseases may be based on potentially protective underlying mechanisms, such as type 2 airway inflammation, downregulation of ACE2/TMPRSS2 receptors, reduced exposures to triggers and improved adherence to controller medications.
33066495 As such, this paper focuses on the potential role of BPA in promoting comorbidities associated with severe COVID-19, as well as on potential BPA-induced effects on key SARS-CoV-2 infection mediators, such as angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2).
33067518 The binding affinity and adhesive strength between the spike (S) glycoproteins of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the human angiotensin-converting enzyme 2 (ACE2) receptor is computed using molecular dynamics (MD) simulations. […] Our analysis suggests that only 27 (13 in S-protein, 14 in ACE2) residues are active during the initial fusion process between the S-protein and ACE2 receptor.
33068416 This part of the viral sequence codes for the Spike S protein that interacts with the human receptor angiotensin-converting enzyme 2 (ACE2).
33068560 The aim of this study was to evaluate the effect of ICSs following pulmonary expression of the SARS-CoV-2 viral entry receptor angiotensin-converting enzyme-2 (ACE2). ) and administration of exogenous IFN-β were used to study the functional role of type-I interferon signaling in ACE2 expression. […] We compared sputum ACE2 expression in patients with COPD stratified according to use or nonuse of ICS. mice had reduced ACE2 expression, indicating that type I interferon contributes mechanistically to this effect. […] ICS administration attenuated expression of ACE2 in airway epithelial cell cultures from patients with COPD and in mice with elastase-induced COPD-like changes. […] Compared with ICS nonusers, patients with COPD who were taking ICSs also had reduced sputum expression of ACE2. […] ICS therapies in COPD reduce expression of the SARS-CoV-2 entry receptor ACE2.
33069360 Most of the SARS-CoV-2 neutralizing antibodies to date target the spike (S) protein receptor binding domain (RBD), which engages the host receptor ACE2 for viral entry.
33069705 In here, exploiting a large panel of publicly available genome-wide data, we investigated whether the human receptor ACE2 and human proteases TMPRSS2, FURIN and CATHEPSINs (B, L and V), which are involved in SARS-CoV-2 cell entry, are transcriptionally regulated by environmental cues. […] We report that more than 50 chemicals modulate the expression of ACE2 or human proteases important for SARS-CoV-2 cell entry.
33070537 There is growing evidence to suggest that the angiotensin converting enzyme 2 receptor (ACE2 receptor) is expressed on endothelial cells (ECs) in the lung, heart, kidney, and intestine, particularly in systemic vessels (small and large arteries, veins, venules, and capillaries).
33071815 results suggest that the dysregulated lipogenesis and the subsequently high ACE2 expression in obese patients might be the mechanism underlying the increased risk for severe complications in those patients when infected by SARS-CoV-2.
33072093 SARS-CoV-2 infection is mediated by the binding of viral Spike proteins (S-protein) to human cells through a 2-step process, which involves Angiotensin Converting Enzyme-2 (ACE2) and Transmembrane Serine Protease (TMPRSS)-2. […] Therefore, the development of novel inhibitors of ACE2/TMPRSS2 is likely to be beneficial in combating SARS-CoV-2 infections.
33072222 interactions with the host cell angiotensin-converting enzyme 2 (ACE2) PD domain. […] We utilized the information from ACE2-SARS-CoV-2 binary interactions, and based on crucial interacting interface residues, novel peptidomimetics were designed. […] Top scoring peptidomimetics were found to bind at the ACE2 binding site of the receptor-binding domain (RBD) of SARS-CoV-2 spike protein.
33072499 Together with data from screening by comprehensive 2D angiotensin-converting enzyme 2 (ACE2) biochromatography, 8 components in LHQW that were exposed to human and had potential ACE2 targeting ability were identified for further pharmacodynamic evaluation. […] Results show that rhein, forsythoside A, forsythoside I, neochlorogenic acid and its isomers exhibited high inhibitory effect on ACE2.
33072500 Angiotensin-converting enzyme 2 (ACE2) was rapidly identified as the critical functional receptor for SARS-CoV-2. […] ACE2 is well-known as a counter-regulator of the renin-angiotensin system (RAS) and plays a key role in the cardiovascular system. […] Given that ACE2 functions as both a SARS-CoV-2 receptor and a RAS modulator, the treatment for COVID-19 presents a dilemma of how to limit virus entry but protect ACE2 physiological functions. […] Thus, an in-depth summary of the recent progress of ACE2 research and its relationship to the virus is urgently needed to provide possible solution to the dilemma. […] Here, we summarize the complexity and interplay between the coronavirus, ACE2 and RAS (including anti-RAS drugs). […] We propose five novel working modes for functional receptor for SARS-CoV-2 infection and the routes of ACE2-mediated virus entering host cells, as well as its regulatory mechanism. […] These will contribute to a deeper understanding of the complex mechanisms of underlying the relationship between the virus and ACE2, and provide guidance for virus intervention strategies.
33072849 Genes exhibiting most variable expression include ACE2, CLEC4G, CLEC4M, CD209 (interact with the SARS-CoV-2 spike protein); REEP6 (a receptor accessory protein expressed in the olfactory epithelium); SLC27A2 and PKP2 (inhibit virus replication); and PTGS2 (mediates fever response). […] The most significant age-dependent gene is ACE2, the cellular receptor of SARS-CoV-2.
33073699 Therefore, this study was planned to investigate the antiviral role of the active constituents against spike glycoprotein of SARS-CoV-2 as well as its host ACE2 receptor. […] The results suggested that amarogentin, eufoliatorin, α-amyrin, caesalpinins, kutkin, β-sitosterol, and belladonnine are the top-ranked molecules have the highest affinity towards both the spike glycoprotein and ACE2.
33073716 The most established mechanism of viral entry into the body is considered to be via angiotensin-converting enzyme 2 (ACE2) acting as a receptor for viral spike protein thereby facilitating its entry in the cell. […] However, ACE2 is also involved in providing the protection from severe pathological changes. […] This article provides a computational and bioinformatics-based analysis of ACE2 with an objective of providing further insight into the earnest efforts to determine its true position in COVID-19 pathology. […] The results of this study show that ACE2 has strikingly low expression in healthy human lung tissue and was absent from the list of differentially expressed genes. […] Moreover, the miRNA prediction analysis revealed that miR-1246, whose upregulation has been experimentally established to be a cause of acute respiratory distress syndrome (ARDS), was found to be targeting the coding DNA sequence (CDS) of ACE2. […] This study presents a wide range of potentially important transcription factors as well as miRNA targets associated with ACE2 which can be potentially used for drug designing amid this challenging pandemic situation.
33073910 To analyse ACE2 expression in salivary glands, bulk RNA-seq profiles from four public datasets including 31 COVID-19 patients were recruited. […] ACE2 expression was present at detectable levels in the salivary glands. […] This study confirms the expression of ACE2 in the salivary glands and demonstrates the possibility of SARS-CoV-2 infection of salivary glands.
33073969 SARS-CoV-2 mainly affects the tissues expressing angiotensinconverting enzyme 2 (ACE2). […] ACE2 is used as a receptor for the virus to enter the cells.
33074885 Surgically resected specimens of the cases with confirmed COVID-19 were obtained to detect the expression of ACE2 and the presence of SARS-CoV-2.
33077836 Angiotensin converting enzyme 2 (ACE2) (EC: is a transmembrane protein which is considered as a receptor for spike protein binding of novel coronavirus (SARS-CoV2). […] In this paper five phytochemicals, which belong to flavonoid and anthraquinone subclass, have been selected as small molecules in molecular docking study of spike protein of SARS-CoV2 with its human receptor ACE2 molecule. […] Among them, the phytochemical hesperidin can bind with ACE2 protein and bound structure of ACE2 protein and spike protein of SARS-CoV2 noncompetitively. […] The binding sites of ACE2 protein for spike protein and hesperidin, are located in different parts of ACE2 protein. […] Ligand spike protein causes conformational change in three-dimensional structure of protein ACE2, which is confirmed by molecular docking and molecular dynamics studies. […] This compound modulates the binding energy of bound structure of ACE2 and spike protein. […] This result indicates that due to presence of hesperidin, the bound structure of ACE2 and spike protein fragment becomes unstable.
33077899 The plant-produced RBD exhibited specific binding to the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2).
33077915 Angiotensin-converting enzyme 2 (ACE2) is an entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and a regulator of several physiological processes. […] ACE2 has recently been proposed to be interferon (IFN) inducible, suggesting that SARS-CoV-2 may exploit this phenomenon to enhance viral spread and questioning the efficacy of IFN treatment in coronavirus disease 2019. […] Using a recent de novo transcript assembly that captured previously unannotated transcripts, we describe a new isoform of ACE2, generated by co-option of intronic retroelements as promoter and alternative exon. […] The new transcript, termed MIRb-ACE2, exhibits specific expression patterns across the aerodigestive and gastrointestinal tracts and is highly responsive to IFN stimulation. […] In contrast, canonical ACE2 expression is unresponsive to IFN stimulation. […] Moreover, the MIRb-ACE2 translation product is a truncated, unstable ACE2 form, lacking domains required for SARS-CoV-2 binding and is therefore unlikely to contribute to or enhance viral infection.
33077916 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, utilizes angiotensin-converting enzyme 2 (ACE2) for entry into target cells. […] ACE2 has been proposed as an interferon-stimulated gene (ISG). […] Thus, interferon-induced variability in ACE2 expression levels could be important for susceptibility to COVID-19 or its outcomes. […] Here, we report the discovery of a novel, transcriptionally independent truncated isoform of ACE2, which we designate as deltaACE2 (dACE2). […] We demonstrate that dACE2, but not ACE2, is an ISG. […] In The Cancer Genome Atlas, the expression of dACE2 was enriched in squamous tumors of the respiratory, gastrointestinal and urogenital tracts. […] In vitro, dACE2, which lacks 356 amino-terminal amino acids, was non-functional in binding the SARS-CoV-2 spike protein and as a carboxypeptidase. […] Our results suggest that the ISG-type induction of dACE2 in IFN-high conditions created by treatments, an inflammatory tumor microenvironment or viral co-infections is unlikely to increase the cellular entry of SARS-CoV-2 and promote infection.
33078028 Although SARS-CoV-2 primarily causes respiratory infection by binding to ACE2 receptors present on alveolar epithelial cells, studies have been published linking the disease to the small intestine enterocytes and its microbiome.
33078369 COVID-19 and AD share common links with respect to angiotensin-converting enzyme 2 (ACE2) receptors and pro-inflammatory markers such as interleukin-1 (IL-1), IL-6, cytoskeleton-associated protein 4 (CKAP4), galectin-9 (GAL-9 or Gal-9), and APOE4 allele.
33078623 Angiotensin-converting enzyme 2 (ACE2) facilitates the cellular entry of the severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2), which causes the coronavirus-2019 (COVID-19) disease. […] We review the hypothesis that sex-related differences in outcomes in COVID-19 are due to different activity of ACE2 between men and women. […] We also show that studies in humans have demonstrated no significant difference in serum ACE2 levels between healthy men and women. […] However, men with hypertension and heart failure typically have higher level of serum ACE2 activity compared to women.
33080267 Angiotensin-converting enzyme 2 (ACE2) is the entry receptor for SARS-CoV-2, and recombinant ACE2 decoys are being evaluated as new antiviral therapies. […] We designed and tested an antibody-like ACE2-Fc fusion protein, which has the benefit of long pharmacological half-life and the potential to facilitate immune clearance of the virus. […] Out of a concern that the intrinsic catalytic activity of ACE2 may unintentionally alter the balance of its hormonal substrates and cause adverse cardiovascular effects in treatment, we performed a mutagenesis screening for inactivating the enzyme. […] This study established new ACE2-Fc candidates as antiviral treatment for SARS-CoV-2 without potentially harmful side effects from ACE2’s catalytic actions toward its vasoactive substrates.
33080900 interaction of angiotensin-converting enzyme 2 (ACE2) human receptor with two bioactive compounds, i.e., nicotine and caffeine, via molecular dynamic (MD) simulations. […] The simulations reveal the efficient blocking of ACE2 by caffeine and nicotine in the exposure to the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). […] We have selected the two most important active sites of ACE2-S protein, i.e., 6LZG and 6VW1, which are critically responsible in the interaction of S protein to the receptor and thus, we investigated their interaction with nicotine and caffeine through MD simulations. […] Further, we investigated the interaction of ACE2 receptor- S protein with nicotine or caffeine when mixed with candidate or approved antiviral drugs for SARS-CoV-2 therapy. […] Our MD simulations suggest that the combination of caffeine with ribavirin shows a stronger interaction with 6VW1, while in case of favipiravir+nicotine, 6LZG shows potent efficacy of these interaction, proposing the potent efficacy of these combinations for blocking ACE2 receptor against SARS-CoV-2.
33081421 To address the expression pattern of the SARS-CoV-2 receptor ACE2 and the viral priming protease TMPRSS2 in the respiratory tract, this study investigated RNA sequencing transcriptome profiling of samples of airway and oral mucosa. […] As shown, ACE2 has medium levels of expression in both small airway epithelium and masticatory mucosa, and high levels of expression in nasal epithelium. […] The expression of ACE2 is low in mucosal-associated invariant T (MAIT) cells and cannot be detected in alveolar macrophages.
33081670 Several studies have indicated that the downregulation of membrane-bound ACE2 may exert a key role for the impairment of immune functions and for COVID-19 patients’ outcome. […] The downregulation may occur by distinct mecha-nisms, particularly: (1) the shedding process induced by SARS-CoV-2 fusion pathway, which reduces the amount of mem-brane-bound ACE2, stimulating more shedding by the high levels of Angiotensin II; (2) the endocytosis of ACE2 receptor with the virus itself and (3) by the interferon inhibition caused by SARS-CoV-2 effects on immune system, which leads to reduction of ACE2 receptor expression. […] Recent research provides evidence of a reduction of the components of the alternative RAS axis, including ACE2 and Angiotensin-(1-7).
33081905 The possible mechanism is that metformin could inhibit cytokine storm via suppressing interleukin-6 (IL-6) signaling, prevent the process of lung fibrosis, suppress endocytosis, thereby elevating angiotensin converting enzyme 2 (ACE2) expression.
33082267 ACE2 has emerged as a double agent in the COVID-19 ordeal, as it is both physiologically protective and virally conducive. […] The identification of ACE2 in as many as 72 tissues suggests that extrapulmonary invasion and damage is likely, which indeed has already been demonstrated by cardiovascular and gastrointestinal symptoms. […] On the other hand, identifying ACE2 dysregulation in patients with comorbidities may offer insight as to why COVID-19 symptoms are often more severe in these individuals. […] This may be attributed to a pre-existing proinflammatory state that is further propelled with the cytokine storm induced by SARS-CoV-2 infection or the loss of functional ACE2 expression as a result of viral internalization. […] Here, we aim to characterize the distribution and role of ACE2 in various organs to highlight the scope of damage that may arise upon SARS-CoV-2 invasion. […] Furthermore, by examining the disruption of ACE2 in several comorbid diseases, we offer insight into potential causes of increased severity of COVID-19 symptoms in certain individuals. […] SIGNIFICANCE STATEMENT: Cell surface expression of ACE2 determines the tissue susceptibility for coronavirus infectious disease 2019 infection. […] Comorbid disease conditions altering ACE2 expression could increase the patient’s vulnerability for the disease and its complications, either directly, through modulation of viral infection, or indirectly, through alteration of inflammatory status.
33082395 Here, we analyzed published RNA-seq datasets and demonstrated that cells of four different lung epithelial stem cell types express SARS-CoV-2 entry factors, including Ace2.
33082473 Previously, we described a strategy to rapidly identify and generate llama nanobodies (VHH) from naïve and synthetic humanized VHH phage libraries that specifically bind the S1 SARS-CoV-2 spike protein, and block the interaction with the human ACE2 receptor. […] The resulting tri-specific VHH-Fc antibodies show more potent S1 binding, S1/ACE2 blocking, and SARS-CoV-2 pseudovirus neutralization than the bi-specific VHH-Fcs or combination of individual monoclonal VHH-Fcs.
33082574 A cryo-EM structure of the trivalent VH bound to Spike shows each VH domain engaging an RBD at the ACE2 binding site, confirming our original design strategy.
33083627 Molecular docking of shortlisted lead compounds was performed using AutoDock Vina and interacting residues were visualized. analysis, the lead compounds scrutinized herewith interact with S, hence, can prevent its internalization in cell using ACE2 and GRP78 receptor.The compounds predicted in this study are based on rigorous computational analysis and the evaluation of predicted lead compounds can be promising in experimental studies.
33083782 The SARS-CoV-2 is dependent on binding to the angiotensin converting enzyme 2 (ACE2), which is part of the renin-angiotensin system (RAS). […] Downregulation of ACE2 upon virus binding disturbs downstream activities of RAS resulting in increased inflammation and development of fibrosis. […] The poor prognosis and risk of developing pulmonary fibrosis are therefore associated with the increased expression of ACE2 in risk groups, such as obesity, heart disorders and aging, conferring plenty of binding opportunity for the virus and subsequently the internalization of ACE2, thus devoiding the enzyme from acting counter-inflammatory and antifibrotic.
33084001 Some physicians have considered the need for interrupting RAAS inhibition in order to reduce the possibility of SARS-CoV2 entering lung cells after binding to angiotensin-converting enzyme 2 (ACE2) receptors.
33084449 The spike (S) of SARS coronavirus 2 (SARS-CoV-2) engages angiotensin-converting enzyme 2 (ACE2) on a host cell to trigger viral-cell membrane fusion and infection. […] The extracellular region of ACE2 can be administered as a soluble decoy to compete for binding sites on the receptor-binding domain (RBD) of S, but it has only moderate affinity and efficacy. […] A deep mutational scan of ACE2 expressed on human cells identified mutations that increase S affinity and guided the engineering of a potent and broad soluble receptor decoy.
33085491 Human angiotensin-converting enzyme 2 (ACE2) was recently recognized as the transmembrane protein that serves as the point of entry of SARS-CoV-2 into cells, thus constituting the first biomolecular event leading to COVID-19 disease. […] Moreover, the free energy of binding between ACE2 and the active receptor binding domain of the SARS-CoV-2 spike protein is evaluated quantitatively, providing for the first time the thermodynamics of virus-receptor recognition. […] Furthermore, the action of different ACE2 ligands is also examined in particular in their capacity to disrupt SARS-CoV-2 recognition, also providing via a free energy profile the quantification of the ligand-induced decreased affinity.
33086029 receptor axis towards a protective ACE2/Ang (1-7)/Mas receptor axis.
33088807 Angiotensin-converting enzyme 2 (ACE2) plays a pivotal role in the renin-angiotensin system and is closely related to coronavirus disease of 2019. […] However, the role of ACE2 in cancers remains unclear. […] We explored the pan-cancer expression patterns and prognostic value of ACE2 across multiple databases, including Oncomine, PrognoScan, Gene Expression Profiling Interactive Analysis, and Kaplan-Meier Plotter. […] Then, we investigated the correlations between ACE2 expression and immune infiltration in cancers. […] We found that tumor tissues had higher expression levels of ACE2 compared with normal tissue in the kidney and the liver and lower expression levels in the lung. […] High expression levels of ACE2 were beneficial to survival in ovarian serous cystadenocarcinoma, liver hepatocellular carcinoma, kidney renal papillary cell carcinoma, and kidney renal clear cell carcinoma, although this was not the case in lung squamous cell carcinoma. […] For those with a better prognosis, there were significant positive correlations between ACE2 expression and immune infiltrates, including B cells, CD8 + T cells, CD4 + T cells, neutrophils, macrophages, and dendritic cells. […] In conclusion, ACE2 could serve as a pan-cancer prognostic biomarker and is correlated with immune infiltrates.
33089452 We examined the expression of ACE2, to which SARS-CoV-2 Spike (S) protein binds to facilitate viral entry, in cord blood derived HSCs/HPCs and in peripheral blood derived immune cell subtypes. […] ACE2 is expressed in low numbers of immune cells, higher numbers of HPCs, and up to 65% of rigorously defined HSCs. […] Graphical Abstract • Human HSCs, HPCs, and immune cells express ACE2 on the cell surface, making them potentially susceptible to SARS-CoV-2 infection. […] • SARS-CoV-2 S protein, which binds to ACE2, induces defects in the colony forming capacity of human HPC and inhibits the expansion of HSC/HPC subpopulations ex vivo. […] These effects can be at least partially neutralized by treatment with SARS-CoV-2 targeting antibody, recombinant human ACE2, or Angiotensin1-7.
33090438 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) uses Angiotensin- converting enzyme 2 (ACE2) receptors to infect host cells which may lead to coronavirus disease (COVID-19). […] Given the presence of ACE2 receptors in the brain and the critical role of the renin-angiotensin system (RAS) in brain functions, special attention to brain microcirculation and neuronal inflammation is warranted during COVID-19 treatment.
33091066 Additionally, we identified 18 mutations in the SARS-CoV-2 spike glycoprotein and a few selected mutations showed to increase stability, binding affinity, and molecular flexibility in the overall tertiary structure of the protein that may facilitate interaction between the receptor binding domain (RBD) of spike protein and the human angiotensin-converting enzyme 2 (ACE2) receptor.
33091382 Probe regions include full-length spike ectodomain as well as various subregions, and we also design mutants that eliminate recognition of the angiotensin-converting enzyme 2 (ACE2) receptor. […] Probes are characterized for antigenicity and ACE2 recognition, and the structure of the spike ectodomain probe is determined by cryoelectron microscopy.
33091416 Both SARS-CoV-2 and SARS-CoV-1 in 2002 share the same receptor angiotensin-converting enzyme 2 (ACE2), which can be found in the brain and mediate the disease process.
33091590 The virus first infects the lower airway and bind with angiotensin-converting enzyme 2 (ACE2) of alveolar epithelial cells.
33092787 In time, the coronaviruses that bats host as reservoirs have undergone recombination and other modifications that have increased their ability for inter-species transmission: one modification of particular importance has been the development of the ability to use ACE2 as a receptor in host cells.
33092925 Besides, E-M could bind with the residues His34, Phe28, Thr27, Ala36, Asp355, Glu37, Gln24, Ser19, Tyr83, and Tyr41 of ACE2. […] Hydrogen bonds and electrostatic interactions may play vital roles in blocking the receptor ACE2 binding with SARS-CoV-2.
33093202 An essential mechanism for severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection begins with the viral spike protein binding to the human receptor protein angiotensin-converting enzyme II (ACE2). […] Here, we describe a stepwise engineering approach to generate a set of affinity optimized, enzymatically inactivated ACE2 variants that potently block SARS-CoV-2 infection of cells. […] We first computationally designed the ACE2-RBD interface using a two-stage flexible protein backbone design process that improved affinity for the RBD by up to 12-fold. […] The highest-affinity variant contained seven amino acid changes and bound to the RBD 170-fold more tightly than wild-type ACE2. […] With the addition of the natural ACE2 collectrin domain and fusion to a human immunoglobulin crystallizable fragment (Fc) domain for increased stabilization and avidity, the most optimal ACE2 receptor traps neutralized SARS-CoV-2-pseudotyped lentivirus and authentic SARS-CoV-2 virus with half-maximal inhibitory concentrations (IC50s) in the 10- to 100-ng/mL range. […] Engineered ACE2 receptor traps offer a promising route to fighting infections by SARS-CoV-2 and other ACE2-using coronaviruses, with the key advantage that viral resistance would also likely impair viral entry.
33095007 Based on the binding affinity and interaction, 15 peptides were selected, which showed higher affinity compared to the α-helix of the human ACE2 receptor.
33097186 Given that angiotensin I converting enzyme 2 (ACE2) is the viral entry molecule, understanding ACE2 has become a major focus of current COVID-19 research. […] ACE2 is highly expressed in the gut, but its role has not been fully understood and thus COVID-19 treatments intending to downregulate ACE2 level may cause untoward side effects. […] Gaining insight into the functions of ACE2 in gut homeostasis therefore merits closer examination, and is beneficial to find potential therapeutic alternatives for COVID-19. […] We took advantage of Ace2 knockout out mice and isolated intestinal organoids to examine the role of ACE2 in intestinal stemness. […] Our data reveal that ACE2 contributes to the proliferation of intestinal stem cells and hence orchestrates the mucosal homeostasis.
33099241 This is the first study to detect SARS-CoV-2 S1 antigen using an LFIA with matched pair consisting of ACE2 and antibody.
33100642 The virus causes multiorgan damage and primarily damages airway epithelium, small intestine epithelium, and vascular endothelium, which are organs with high angiotensin-converting enzyme (angiotensin-converting enzyme-2 [ACE2] expression).
33101066 Plasma ACE, ACE2, and Ang-(1-7) levels, and ACE2 activity were significantly higher in normal pregnant women compared with non-pregnant women; neprilysin (NEP) levels were not changed. […] In SGA pregnancies, ACE and ACE2 levels were higher in early-mid pregnancy compared with normal pregnant women. […] In women with PE, plasma ACE, ACE2, NEP, and Ang-(1-7) levels and ACE2 activity were lower than levels in normal pregnant women. […] The higher plasma ACE2 levels and activity in pregnancy could be driving the higher Ang-(1-7) levels. […] The early gestation increases in ACE and ACE2 levels in SGA pregnancies highlights the possibility that these enzymes could be used as potential early biomarkers of poor fetal growth. […] In women with PE, the reduced ACE2 and NEP levels at term, could be contributing to the reduction in Ang-(1-7) levels. […] Since soluble ACE2 can prevent binding of the novel coronavirus, SARS-CoV-2, to membrane bound ACE2, the interplay between ACE2 and the coronavirus and its impact in pregnancy requires further investigation.
33101175 In the past two hitherto similar CoVs, the severe acute respiratory syndrome CoV (SARS-CoV-1) and Middle East respiratory syndrome CoV (MERS-CoV) also gained universal attention as they produced clinical symptoms similar to those of SARS-CoV-2 utilizing angiotensin-converting enzyme 2 (ACE2) receptor and dipeptidyl peptidase 4 (DPP4) to go into the cells. […] The proper understanding of the expression and dissemination of ACE2 in central and peripheral nerve systems is crucial to understand better the neurological morbidity caused by COVID-19. […] We correlate ACE2 to the pathogenesis and neurologic complications of COVID-19 and found that SAMHD1 links to NF-κB pathway.
33101246 The primary focus has been on the angiotensin-converting enzyme 2 (ACE2), which is a host cell receptor for SARS-CoV-2. […] Among investigated species, irrespective of ACE2 spike protein binding, only mild (or no) disease has occurred following infection with SARS-CoV-2, suggesting that ACE2 may be necessary for infection but is not sufficient to determine the outcome of infection. […] Healthy pigs express ACE2 protein that binds the viral spike protein but they are not susceptible to infection with SARS-CoV-2.
33101829 approach to predict the potential animals range with high susceptibility to SARS-CoV-2 by modelling and studying the Spike-ACE2 interaction of 22 domestic and wild animals. […] Our results showed that all studied animals are potentially susceptible to SARS-CoV-2 infection with a slight difference in the binding affinity and stability of their ACE2-RBD complexes. […] Furthermore, we identified a specific substitution of tyrosine to histidine at position 41 in ACE2 that likely reduces the affinity to SARS-CoV-2 in horses and greater horseshoe bats.
33102950 Many efforts to design and screen therapeutics for the current severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic have focused on inhibiting viral host cell entry by disrupting angiotensin-converting enzyme-2 (ACE2) binding with the SARS-CoV-2 spike protein. […] This work focuses on the potential to inhibit SARS-CoV-2 entry through a hypothesized α5β1 integrin-based mechanism and indicates that inhibiting the spike protein interaction with α5β1 integrin (+/- ACE2) and the interaction between α5β1 integrin and ACE2 using a novel molecule (ATN-161) represents a promising approach to treat coronavirus disease-19.
33103220 The first interaction between the virus and the host cell is mediated by the spike protein on the virus surface and the human angiotensin-converting enzyme (ACE2). […] Small molecules able to bind the receptor-binding domain (RBD) of the spike protein and disrupt the binding to ACE2 would offer an important tool for slowing, or even preventing, the infection. […] Out of six drugs characterized as putative RBD binders, the cephalosporin antibiotic cefsulodin was further assessed for its effect on the binding between the RBD and ACE2, suggesting that it is important to consider the dynamic formation of the heterodimer between RBD and ACE2 when judging any potential candidate.
33103586 and has potential to act as an interfering compound between viral spike-host ACE2 interactions.
33103998 The Spike protein of SARS-CoV-2, its receptor-binding domain (RBD), and its primary receptor ACE2 are extensively glycosylated. […] We expressed different glycoforms of the Spike-protein and ACE2 in CRISPR-Cas9 glycoengineered cells, and developed corresponding SARS-CoV-2 pseudovirus. […] We observed that N- and O-glycans had only minor contribution to Spike-ACE2 binding. […] Blocking N-glycan biosynthesis at the oligomannose stage using both genetic approaches and the small molecule kifunensine dramatically reduced viral entry into ACE2 expressing HEK293T cells. […] This could reduce RBD presentation on virus, lowering binding to host ACE2 and decreasing viral entry.
33105685 Despite similarities based on cryo-EM and biochemical studies, the SARS-CoV-2 shows higher stability and binding affinity to the ACE2 receptor.
33105869 The spike glycoprotein has drawn considerable attention as a means to block viral entry owing to its interactions with the human angiotensin-converting enzyme 2 (ACE2), which acts as a receptor. […] Here, we review the current knowledge of SARS-CoV-2 and its interactions with ACE2 and antibodies. […] Structural information of SARS-CoV-2 spike glycoprotein and its complexes with ACE2 and antibodies can provide key input for the development of therapies and vaccines against the new coronavirus.
33106680 Unfortunately, SARS-CoV-2 infects mice only if they have been genetically modified to express human ACE2.
33106832 The virus infects lung cells by binding angiotensin-converting enzyme 2 (ACE2) of cell surface, which leads to leukocyte infiltration, increased permeability of blood vessels and alveolar walls, and decreased surfactant in the lung, causing respiratory symptoms.
33108789 The coronavirus disease 2019 (COVID-19) infection, caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), involves several organs through participation of angiotensin-conversion enzyme 2 (ACE2) receptors. […] The presence of ACE2 receptors in the liver renders this organ a potential target for the novel coronavirus.
33108833 The virus employs the angiotensin-converting enzyme 2 (ACE2) receptor for entry into human cells. […] ACE2 is expressed on different organs, which is raising concern as to whether these organs can be infected by the virus or not. […] The testis appears to be an organ enriched with levels of ACE2, while the possible mechanisms of involvement of the male reproductive system by SARS-CoV-2 are not fully elucidated. […] The aim of this review was to provide new insights into different possible mechanisms of involvement of male gonads with SARS-CoV-2 including investigating the ACE2 axis in testis, hormonal alterations in patients with COVID-19, possible formation of anti-sperm antibodies (ASA) and subsequently immunological infertility as a complication of SARS-CoV-2 infection. […] Once infected, changes in ACE2 signalling pathways followed by oxidative stress and inflammation could cause spermatogenesis failure, abnormal sperm motility, DNA fragmentation and male infertility.
33108902 Considering the limited data on cancer patients, we analyzed public data repositories limited to investigate angiotensin-converting enzyme 2 (ACE2) and the transmembrane serine protease 2 (TMPRSS2) expressions and genetic variants to identify the basis of individual susceptibility to SARS-CoV-2. […] Allele frequencies of germline variants were explored in different ethnicities, with a special focus on ACE2 variants located in the binding site to SARS-CoV-2 spike protein.The analysis of ACE2 and TMPRSS2 expressions in healthy tissues showed a higher expression in the age class 20 to 59 years (false discovery rate [FDR] < 0.0001) regardless of gender. […] ACE2 and TMPRSS2 were more expressed in tumors from males than females (both FDR < 0.0001) and, opposite to the regulation in tissues from healthy individuals, more expressed in elderly patients (FDR = 0.005; FDR < 0.0001, respectively). […] ACE2 and TMPRSS2 expressions were higher in cancers of elderly patients compared with healthy individuals (FDR < 0.0001). […] The mechanisms of ACE2 and TMPRSS2 regulation could be targeted for preventive and therapeutic purposes in the whole population and especially in cancer patients.Further studies are needed to show a direct correlation of ACE2 and TMPRSS2 expressions in cancer patients and the incidence of COVID-19.
33110068 The structure reveals that CV30 binds to an epitope that overlaps with the human ACE2 receptor binding motif providing a structural basis for its neutralization.
33110195 The contact surface of the host cell receptor, ACE2, displays amino acid residues that are critical for virus recognition, and variations at these critical residues modulate infection susceptibility. […] Here, we show that all apes and African and Asian monkeys (catarrhines), exhibit the same set of twelve key amino acid residues as human ACE2.
33110240 We discussed a possible link between the activation of hypoxia inducible factor 1α (HIF-1α) and cell entry of SARS-CoV-2, since HIF-1α is shown to suppress the angiotensin-converting enzyme 2 (ACE2) receptor and transmembrane protease serine 2 (TMPRSS2) and upregulate disintegrin and metalloproteinase domain-containing protein 17 (ADAM17).
33110677 The exact reasons why the disease has a milder course in children is unknown but high numbers of Angiotensin Converting Enzyme-2 (ACE2) receptors, underdeveloped immune responses, cross-reaction with other viruses, protective effect of fetal hemoglobin and fewer outdoor activities as well as journeys, and nonexposure to air pollution, and smoking.
33110678 SARS-CoV-2 spike (S) glycoprotein is vital in the binding of the virus to the host cell receptor that is angiotensin converting-enzyme 2 (ACE2), membrane fusion, vaccine studies and immune response to the virus.
33111375 The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is a candidate vaccine antigen that binds angiotensin-converting enzyme 2 (ACE2), leading to virus entry. […] Compared to other vaccine formulations, immunization using CoPoP liposomes admixed with recombinant RBD induces multiple orders of magnitude higher levels of antibody titers in mice that neutralize pseudovirus cell entry, block RBD interaction with ACE2, and inhibit live virus replication.
33112126 In this Review, we discuss the role of primary host factors such as the cell receptor angiotensin-converting enzyme 2 (ACE2), cellular proteases of S protein priming, post-translational modifiers, kinases, inflammatory cells, and their pharmacological intervention in the infection of SARS-CoV-2 and related viruses.
33112147 The spike protein of nCOV-2019 resides on the virion’s surface mediating coronavirus entry into host cells by binding its receptor binding domain (RBD) to the host cell surface receptor protein, angiotensin converter enzyme (ACE2). […] Our goal is to provide a detailed structural mechanism of how nCOV-2019 recognizes and establishes contacts with ACE2 and its difference with an earlier severe acute respiratory syndrome coronavirus (SARS-COV) in 2002 via extensive molecular dynamics (MD) simulations. […] In this study, we investigated the effect of these mutations as well as other Ala-scanning mutations on the stability of the RBD/ACE2 complex. […] It is found that most of the naturally occurring mutations to the RBD either slightly strengthen or have the same binding affinity to ACE2 as the wild-type nCOV-2019. […] Furthermore, in silico Ala-scanning and long-timescale MD simulations highlight the crucial role of the residues at the interface of RBD and ACE2 that may be used as potential pharmacophores for any drug development endeavors.
33112187 Using computational analysis with experimental data, we report that idiopathic pulmonary fibrosis (IPF)- and chronic obstructive pulmonary disease (COPD)-derived lung fibroblasts express higher levels of angiotensin-converting enzyme 2 (ACE2), the receptor for SARS-CoV-2 entry and part of the renin-angiotensin system that is antifibrotic and anti-inflammatory. […] In preclinical models, we found that chronic exposure to cigarette smoke, a risk factor for both COPD and IPF and potentially for SARS-CoV-2 infection, significantly increased pulmonary ACE2 protein expression. […] Further studies are needed to understand the functional implications of ACE2 on lung fibroblasts, a cell type that thus far has received relatively little attention in the context of COVID-19.
33112694 Similar to SARS-CoV-1, cellular entry of SARS-CoV-2 depends on the expression of ACE2, a receptor that is abundantly expressed in the nervous system.
33112891 COVID-19 is caused by a novel coronavirus SARS-CoV-2, which enters human target cells via angiotensin converting enzyme 2 (ACE2). […] We used a number of bioinformatics tools to computationally characterize ACE2 by determining its cell-specific expression in trachea, lung, and small intestine, derive its putative functions, and predict transcriptional regulation. […] The small intestine expressed higher levels of ACE2 mRNA than any other organ. […] Single cell RNA-Seq data from trachea indicated positive signals along the respiratory tract in key protective cell types including club, goblet, proliferating, and ciliary epithelial cells; while in lung the ratio of ACE2-expressing cells was low in all cell types (<2.6%), but was highest in vascular endothelial and goblet cells. […] Gene ontology analysis suggested that, besides its classical role in the renin-angiotensin system, ACE2 may be functionally associated with angiogenesis/blood vessel morphogenesis. […] Using a novel tool for the prediction of transcription factor binding sites we identified several putative binding sites within two tissue-specific promoters of the ACE2 gene as well as a new putative short form of ACE2. […] Our results also confirmed that age and gender play no significant role in the regulation of ACE2 mRNA expression in the lung.
33113348 We find expression of viral receptor ACE2 in mature choroid plexus cells expressing abundant lipoproteins, but not in neurons or other cell types. […] We find that infected cells are apolipoprotein- and ACE2-expressing cells of the choroid plexus epithelial barrier.
33114359 It has been well established that angiotensin-converting enzyme type 2 (ACE2) is the primary cellular receptor for SARS-CoV-2. […] ACE2 belongs to the renin-angiotensin system (RAS), composed of several peptides, such as angiotensin II (Ang II) and angiotensin (1-7) (Ang-(1-7)).
33114495 These different fat types have partially diverging biochemical roles in the human body, and they are differentially associated with SARS-CoV-2, which targets the angiotensin-converting enzyme 2 (ACE2) for cell entry. […] ACE2 is highly expressed in adipose tissue, especially in visceral fat, suggesting an important role for this tissue in determining COVID-19 disease severity.
33115584 Both viruses use the common angiotensin converting enzyme (ACE2) receptor to attach to the epithelial cells of the target organs. […] However, ACE2 has high expression in other human organs such as kidney and testes. […] Thus, it is assumed that, like SARS, it may have adverse effects on other vital organs, which have dominant expression of ACE2. […] Key Words: COVID-19; SARS; ACE2, Testes.
33116037 These drugs are reported to result in unfavorable outcome as they tend to increase the levels of ACE2 which mediates the entry of SARS-CoV-2.
33116139 We investigate the expression and subcellular localization of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), within the upper (nasal) and lower (pulmonary) respiratory tracts of human donors using a diverse panel of banked tissues. […] Here, we report our discovery that the ACE2 receptor protein robustly localizes within the motile cilia of airway epithelial cells, which likely represents the initial or early subcellular site of SARS-CoV-2 viral entry during host respiratory transmission. […] We further determine whether ciliary ACE2 expression in the upper airway is influenced by patient demographics, clinical characteristics, comorbidities, or medication use, and show the first mechanistic evidence that the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs) does not increase susceptibility to SARS-CoV-2 infection through enhancing the expression of ciliary ACE2 receptor.
33116299 We found that multiple colonic cell types, especially enterocytes, express ACE2 and are permissive to SARS-CoV-2 infection.
33116543 Co-administration of fluoxetine in the treatment of COVID19 could be considered due to the possibility of its interaction with ACE2 receptors, immune-modulatory function, and a proper immune response at the right time.
33116692 The renin-angiotensin system (RAS) is the most important regulatory system of electrolyte homeostasis and blood pressure and acts through angiotensin-converting enzyme (ACE)/angiotensin II (Ang II)/Ang II type 1 (AT1) receptor axis and angiotensin-converting enzyme 2 (ACE2)/angiotensin (1-7)/MAS receptor axis. […] SARS-CoV and SARS-CoV-2 enter the host cells by binding with ACE2. […] H5N1 and H7N9 avian influenza viruses reduce the ACE2 level in the body, and EV71 increases Ang II concentration.
33117175 However, a warning from some research reports and National Authorities raised NSAIDs safety concerns because of the supposed induction of angiotensin-converting enzyme 2 (ACE2) levels (the receptor used by SARS-CoV2 to enter host airways cells), the increased risk of bacterial superinfections and masking of disease symptoms.
33117379 Therefore, the occurrence of specific comorbidities associated with renin-angiotensin system (RAS) imbalance mediated by the interaction between angiotensin-converting enzyme 2 (ACE2) and desintegrin and metalloproteinase domain 17 (ADAM17), along with specific genetic factors mainly associated with type II transmembrane serine protease (TMPRSS2) expression, could be decisive for the clinical outcome of COVID-19. […] Indeed, the exacerbated ADAM17-mediated ACE2, TNF-α, and IL-6R secretion emerges as a possible underlying mechanism for the acute inflammatory immune response and the activation of the coagulation cascade. […] Therefore, in this review, we focus on the main pathophysiological aspects of ACE2, ADAM17, and TMPRSS2 host proteins in COVID-19.
33117440 This has been attributed to differences in immunological response, expression of angiotensin-converting enzyme 2 (ACE2), prevalence of comorbidities, and health-related behaviours, such as smoking.
33118327 Recently, SARS-CoV-2 has been identified as the causative factor of viral infection called COVID-19 that belongs to the zoonotic beta coronavirus family known to cause respiratory disorders or viral pneumonia, followed by an extensive attack on organs that express angiotensin-converting enzyme II (ACE2).
33120941 The virus invades human cells through the angiotensin-converting enzyme 2 (ACE2) receptor-driven pathway, primarily targeting the human respiratory tract.
33122196 Human angiotensin-converting enzyme 2(ACE2) was identified as the entry receptor for SARS-CoV-2. […] As a carboxypeptidase, ACE2 cleaves many biological substrates besides angiotensin II to control vasodilatation and vascular permeability. […] Given the nanomolar high affinity between ACE2 and SARS-CoV-2 spike protein, we investigated how this interaction would affect the enzymatic activity of ACE2. […] Surprisingly, SARS-CoV-2 trimeric spike protein increased ACE2 proteolytic activity ∼3-10 fold against model peptide substrates, such as caspase-1 substrate and Bradykinin-analog. […] The enhancement in ACE2 enzymatic function was mediated by the binding of SARS-CoV-2 spike RBD domain. […] These results highlighted the potential for SARS-CoV-2 infection to enhance ACE2 activity, which may be relevant to the cardiovascular symptoms associated with COVID-19.
33122473 Given the fact that coronavirus harnesses spike protein to invade host cells through angiotensin-converting enzyme 2 (ACE2), hence we see if any previous anti-virtual compounds can block spike-ACE2 interaction and inhibit the virus entry.
33122999 Therefore, we carried out immunostainings for ACE2 and TMPRSS2, two proteinases crucial for the entry of SARS-CoV2 into host cells, in the human enteric nervous system (ENS), as well as in the choroid plexus of the lateral ventricles. […] We found that ACE2 and TMPRSS2 are expressed by enteric neurons and glial cells of the small and large intestine, as well as choroid plexus epithelial cells, indicating that these cells meet the molecular requirements for viral entry.
33123031 Expressed on cell membranes in target pulmonary and intestinal host cells, ACE2 serves as an anchor for initial viral homing, binding to COVID-19 spike-protein domains to enable viral entry into cells and subsequent replication. […] Inherent or acquired enhancement of membrane ACE2 expression, likely leads to a higher degree of infection and may explain the predisposition to severe disease among males, diabetics, or patients with respiratory or cardiac diseases. […] Additionally, once attached, viral intracellular translocation and replication leads to depletion of membranal ACE2 through degradation and shedding. […] ACE2 generates Ang 1-7, which serves a critical role in counterbalancing the vasoconstrictive, pro-inflammatory, and pro-coagulant effects of ACE-induced Ang II. […] Our understanding of COVID-ACE2 associations is incomplete, and some conceptual formulations are currently speculative, leading to controversies over issues such as the usage of ACE inhibitors or Ang-receptor blockers (ARBs). […] This highlights the importance of focusing on ACE2 physiology in the evaluation and management of COVID-19 disease.
33123616 Hence, a therapeutic value of VNS with respect to SARS-CoV-2 infection risk through ACE2 receptor modulation in intestinal epithelia could not be established.
33124193 Besides, there is a strong positive correlation between viral ORF1ab, ORF6, and angiotensin-converting enzyme 2 (ACE2) expression in human lung cells, implying that ACE2 facilitates SARS-CoV-2 infection and replication in host cells probably through the induction of ORF1ab and ORF6.
33124941 We present a framework for mechanisms of thrombosis in COVID-19 that initially derive from interaction of SARS-CoV-2 with ACE2, resulting in dysregulation of angiotensin signaling and subsequent inflammation and tissue injury.
33125431 Angiotensin-converting enzyme 2 (ACE2) has been implicated in the pathogenesis of chronic kidney disease (CKD) and is a membrane receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease (COVID-19), whereas transmembrane protease, serine 2 (TMPRSS2) is involved in viral attachment. […] Together, tissue expression of ACE2 and TMPRSS2 may determine infection. […] Sex, age, body mass index (BMI), and CKD are clinical risk factors for COVID-19 severity, but the relationships between kidney ACE2 and TMPRSS2 expression and these clinical variables are unknown. […] ACE2 expression was similar in the tubulointerstitium of the two groups, but greater in females than males in HLD (P = 0.005) and CKD (P < 0.0001). […] ACE2 expression was lower in glomeruli of CKD patients compared to HLD (P = 0.0002) and lower in males than females. […] There was a strong relationship between ACE2 and TMPRSS2 expression in the glomerulus (r = 0.51, P < 0.0001). […] In CKD, there was a relationship between tubulointerstitial ACE2 expression and estimated glomerular filtration rate (r = 0.36, P < 0.0001) and age (r = -0.17, P = 0.03), but no relationship with BMI. […] Genes involved in inflammation (CCL2, IL6, and TNF) and fibrosis (COL1A1, TGFB1, and FN1) were inversely correlated with ACE2 expression. […] In summary, kidney expression of ACE2 and TMPRSS2 differs in HLD and CKD. […] ACE2 is related to sex and eGFR. […] ACE2 is also associated with expression of genes implicated in inflammation and fibrosis.
33125439 In addition, this evidence is aligned with published ACE2 entry-receptor (single cell) expression data across the human body to construct a viral distribution and ACE2 receptor body map. […] The main SARS-CoV-2 entry receptor, ACE2, is expressed at different levels in multiple tissues throughout the human body, but its expression levels do not always correspond with SARS-CoV-2 detection, indicating that there is a complex interplay between virus and host.
33125711 Interaction of heparin with spike protein RBD was studied using differential scanning fluorimetry and the inhibition of RBD binding to human ACE2 protein using elisa assays was examined. […] Mechanistically, we observed that heparin binds and destabilizes the RBD protein and furthermore, we show heparin directly inhibits the binding of RBD to the human ACE2 protein receptor. […] UFH acts to directly inhibit binding of spike protein to the human ACE2 protein receptor.
33126048 The entry receptors for SARS-CoV-2 - ACE2 and TMPRSS2 are expressed in placenta.
33126657 Appropriate ACE2 activity might be decisive in preventing immune-induced damage and ensuring tissue repair. […] ACE2 has been identified as a common target for different pathogens. […] Some Coronaviruses, including SARS-CoV-2, also use ACE2 to infiltrate the cells. […] The importance of ACE2 shedding, associated with the release of soluble ACE2 and ADAM17-mediated activation of tumor necrosis factor-α (TNF-α)-signaling is unclear.
33128130 The disease arises from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that binds to angiotensin-converting enzyme 2 (ACE2) receptors on host cells for its internalization.
33128895 Cultured pneumocytes express the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor angiotensin-converting enzyme receptor type-2 (ACE2) and can be infected with virus.
33129966 Angiotensin converting enzyme-2 (ACE2) is known to be expressed on type II pneumocytes. […] As a counter-regulatory arm of the renin-angiotensin system (RAS), ACE2 plays critical roles in the pathogenesis of ARDS and acute lung injury. […] The affinity of the spike protein receptor binding domain (RBD) of SARS-CoV-2 for human ACE2 (hACE2) largely determines the degree of clinical symptoms after infection by SARS-CoV-2. […] Previous studies have shown that regulating the ACE2/RAS system is effective in the treatment of severe acute respiratory syndrome coronavirus (SARS-CoV)-induced ARDS and acute lung injury. […] Since ACE2 is the host cell receptor for both SARS-CoV-2 and SARS-CoV, regulating the ACE2/RAS system may alleviate ARDS and acute lung injury caused by SARS-CoV-2 as well as SARS-CoV. […] Vitamin D was found to affect ACE2, the target of SARS-CoV-2; therefore, we propose that vitamin D might alleviate ARDS and acute lung injury induced by SARS-CoV-2 by modulating ACE2.
33130382 Nisin, a food-grade antimicrobial peptide produced by lactic acid bacteria has been examined for its probable interaction with the human ACE2 (hACE2) receptor, the site where spike protein of SARS-CoV-2 binds. […] Among the eight nisin variants examined, nisin H, nisin Z, nisin U and nisin A showed a significant binding affinity towards hACE2, higher than that of the RBD (receptor binding domain) of the SARS-CoV-2 spike protein. […] The molecular interaction of nisin with hACE2 was investigated by homology modeling and docking studies. […] Further, binding efficiency of the most potent nisin H was evaluated through the interaction of hACE2:nisin H complex with RBD (receptor-binding domain) of SARS-CoV-2 and that of hACE2:RBD complex with nisin H. […] Here, nisin H acted as a potential competitor of RBD to access the hACE2 receptor. […] The study unravels for the first time that a globally used food preservative, nisin has the potential to bind to hACE2.
33132795 Then angiotensin-converting enzyme 2 (ACE2) as the binding site of SARS-CoV‑2 and the possible influence on the disease susceptibility are explained.
33134226 Researchers believe that smoking might increase the severity of infections caused by SARS-CoV-2 by altering the viability and integrity of the BBB, while promoting the expression of ACE2 in endothelial cells, glia, and neurons.
33134395 Angiotensin-converting enzyme 2 (ACE2) which is widely distributed in the human body is implicated in the pathogenesis of malaria, type 2 diabetes mellitus (T2DM), and COVID-19. […] Use of ACE2 by the COVID-19 virus induces inflammation and oxidative stress, which can lead to insulin resistance.
33135055 The S protein of SARS-CoV-2 binds to human angiotensin converting enzyme 2 (hACE2) for entry. […] Herein, we describe glycomic and glycoproteomic analysis of hACE2 expressed in HEK293 cells. […] To deduce the detailed structure of glycan epitopes on hACE2 that may be involved in viral binding, we have characterized the terminal sialic acid linkages, the presence of bisecting GlcNAc, and the pattern of N-glycan fucosylation. […] We have conducted extensive manual interpretation of each glycopeptide and glycan spectrum, in addition to using bioinformatics tools to validate the hACE2 glycosylation. […] Our elucidation of the site-specific glycosylation and its terminal orientations on the hACE2 receptor, along with the modeling of hACE2 glycosylation sites can aid in understanding the intriguing virus-receptor interactions and assist in the development of novel therapeutics to prevent viral entry. […] The relevance of studying the role of ACE2 is further increased due to some recent reports about the varying ACE2 dependent complications with regard to age, sex, race, and pre-existing conditions of COVID-19 patients.
33135082 Furthermore, 2019-nCov penetrates cells similarly to the SARS coronavirus, i.e., through the ACE2 receptor.
33135725 Angiotensin-converting enzyme II (ACE2) is a homologue of angiotensin-converting enzyme discovered in 2000. […] From the initial discovery, it was recognized that the kidneys were organs very rich on ACE2. […] Subsequent studies demonstrated the precise localization of ACE2 within the kidney and the importance of this enzyme in the metabolism of Angiotensin II and the formation of Angiotensin 1-7. […] With the recognition early in 2020 of ACE2 being the main receptor of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), the interest in this protein has dramatically increased. […] In this review, we will focus on kidney ACE2; its localization, its alterations in hypertension, diabetes, the effect of ACE inhibitors and angiotensin type 1 receptor blockers (ARBs) on ACE2 and the potential use of ACE2 recombinant proteins therapeutically for kidney disease. […] The possibility that binding of SARS-CoV-2 to kidney ACE2 plays a role in the kidney manifestations is also briefly discussed.
33137894 SARS-CoV2 infection depends on the host cell Angiotensin-Converting Enzyme-2 (ACE2) and Transmembrane Serine Protease-2 (TMPRSS2), where the virus uses ACE2 for entry and TMPRSS2 for S protein priming.
33139422 Using soluble ACE2, inhibition of antibody binding was demonstrated for S and RBD, and not for NP.
33139569 A high-affinity Fab was selected from one of the libraries and converted to a full-size antibody, IgG1 ab1, which competed with human ACE2 for binding to RBD. […] It potently neutralized replication-competent SARS-CoV-2 but not SARS-CoV, as measured by two different tissue culture assays, as well as a replication-competent mouse ACE2-adapted SARS-CoV-2 in BALB/c mice and native virus in hACE2-expressing transgenic mice showing activity at the lowest tested dose of 2 mg/kg. […] The mechanism of neutralization is by competition with ACE2 but could involve antibody-dependent cellular cytotoxicity (ADCC) as IgG1 ab1 had ADCC activity in vitro.
33139693 SARS-CoV-2 might infect the gastrointestinal tract through its viral receptor angiotensin-converting enzyme 2 (ACE2) and there is increasing evidence of a possible fecal-oral transmission route.
33139905 Neutralizing antibodies targeting the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) block severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry into cells via surface-expressed angiotensin-converting enzyme 2 (ACE2). […] We used a surrogate virus neutralization test (sVNT) and SARS-CoV-2 S protein-pseudotyped vesicular stomatitis virus (VSV) vector-based neutralization assay (pVNT) to assess the degree to which serum antibodies from coronavirus disease 2019 (COVID-19) convalescent patients interfere with the binding of SARS-CoV-2 S to ACE2.
33140034 -glycans at sites N165 and N234 in modulating the conformational dynamics of the spike’s receptor binding domain (RBD), which is responsible for ACE2 recognition. […] This finding is corroborated by biolayer interferometry experiments, which show that deletion of these glycans through N165A and N234A mutations significantly reduces binding to ACE2 as a result of the RBD conformational shift toward the “down” state.
33140636 Cell entry, the fundamental step in cross-species transmission of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), is initiated by the recognition of the host cell angiotensin-converting enzyme-2 (ACE2) receptor by the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2.
33140706 It also displayed a very strong binding affinity with the translation initiation and termination sequence sites of spike (S) protein mRNA of SARS-COV-2, its gene product, and host ACE2 receptor.
33140827 ACE2 is a type I membrane protein with extracellular carboxypeptidase activity displaying a broad tissue distribution with highest expression levels at the brush border membrane (BBM) of small intestine enterocytes and a lower expression in stomach and colon. […] In small intestinal mucosa, ACE2 mRNA expression appears to increase with age and to display higher levels in patients taking ACE-inhibitors (ACE-I). […] There, ACE2 protein heterodimerizes with the neutral amino acid transporter Broad neutral Amino acid Transporter 1 (B0AT1) (SLC6A19) or the imino acid transporter Sodium-dependent Imino Transporter 1 (SIT1) (SLC6A20), associations that are required for the surface expression of these transport proteins. […] The heterodimerization of the carboxypeptidase ACE2 with B0AT1 is suggested to favor the direct supply of substrate amino acids to the transporter, but whether this association impacts the ability of ACE2 to mediate viral infection is not known. […] Correspondingly, the lack of ACE2 and the concurrent absence of B0AT1 expression in small intestine causes a decrease in l-tryptophan absorption, niacin deficiency, decreased intestinal antimicrobial peptide production, and increased susceptibility to inflammatory bowel disease (IBD) in mice. […] Thus, the abundant expression of ACE2 in small intestine and its association with amino acid transporters appears to play a crucial role for the digestion of peptides and the absorption of amino acids and, thereby, for the maintenance of structural and functional gut integrity.
33141332 The current body of evidence indicates that SARS-CoV‑2 requires the membrane-bound angiotensin-converting enzyme 2 (ACE2) and the membrane-bound serine protease TMPRSS2 to enter cells. […] Recent studies suggest that COVID-19 patients rarely exhibit viral RNA in tear film and conjunctival smears and that, ACE2 and TMPRSS2 are only expressed in small amounts in the conjunctiva, making conjunctival infection with SARS-CoV‑2 via these mediators unlikely.
33142370 Binding of SARS-CoV-2 to the angiotensin-converting enzyme 2 (ACE2) is a vital pathway for the virus entry into human cells, including those of the respiratory mucosa, esophageal epithelium as well as the absorptive enterocytes from ileum and colon. […] The interaction between SARS-CoV-2 and ACE2 receptor may decrease the receptor expression and disrupt the function of B0AT1 transporter influencing the diarrhea observed in COVID-19 patients.
33142989 through the ACE2 complex. […] We propose a paradigm for the two-site attack of SARS-CoV-2 leading to ENaC hyperactivation and inactivation of the ACE2 complex, which collapses cell osmolality and leads to rupture and/or necrotic death of swollen pulmonary, endothelial, and cardiac cells, thrombosis in infected and non-infected tissues, and aberrant sensory and neurological perception in COVID-19 patients.
33143053 The two main co-factors needed by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to enter human cells are angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2).
33144890 Then angiotensin-converting enzyme 2 (ACE2) as the binding site of SARS-CoV‑2 and the possible influence on disease susceptibility are explained.
33145296 Current studies have found that angiotensin-converting enzyme 2 (ACE2) is a cell surface receptor of the novel coronavirus that plays a vital role in the pathogenesis of COVID-19. […] It is of immense importance for the prevention of virus transmission and treatment to clarify the distribution and expression of ACE2 in various tissues and organs of the body. […] We separately analyzed the distribution of ACE2 expression in different tissues in the GTEx and TCGA database, and explored the correlation between sex and ACE2 expression levels. […] Next, the expression levels of ACE2 in different tissues and organs and its correlation with sex were analyzed once again after combing all samples from the two databases. […] ACE2 expression data were collected from the GTEx database for 6738 normal tissues. […] The results indicated that the expression of ACE2 was the highest in the small intestines, higher in tissues such as salivary glands in the testicular, kidney, heart, thyroid and adipose tissues, while the expression of ACE2 was lower in tissues such as the spleen, brain, muscle, pituitary, and skin. […] There were no significant differences in the expression of ACE2 in the different organs when it came to the individual’s sex. […] Our study deeply explored the distribution and expression of ACE2 in various tissues of the human body. […] The tissues and organs with high ACE2 expression were consistent with the current clinical and basic research results of the novel coronavirus.
33146070 Since the cellular entry of SARS-CoV-2 is accomplished by binding of the spike glycoprotein binding domain (RBD) to the human angiotensin-converting enzyme 2 (hACE2), a molecule that can bind to the spike RDB-hACE2 interface could block the virus entry. […] Here, we performed a virtual screening of 55 compounds to identify potential molecules that can bind to the spike glycoprotein and spike-ACE2 complex interface. […] It was found that the compound ethyl 1-{3-[(2,4-dichlorobenzyl) carbamoyl]-1-ethyl-6-fluoro-4-oxo-1,4-dihydro-7-quinolinyl}-4-piperidine carboxylate (the S54 ligand) and ethyl 1-{3-[(2,4-dichlorobenzyl) carbamoyl]-1-ethyl-6-fluoro-4-oxo-1,4-dihydro-7-quinolinyl}-4 piperazine carboxylate (the S55 ligand) forms hydrophobic interactions with Tyr41A, Tyr505B and Tyr553B, Leu29A, Phe495B, respectively of the spike glycoprotein, the hotspot residues in the spike glycoprotein RBD-hACE2 binding interface.
33146371 Like ACE, the human homologue ACE2 is also involved in blood pressure regulation and cleaves a range of substrates involved in different physiological processes. […] Understanding the interaction between SARS-CoV-2 and ACE2 is crucial for the design of therapies to combat this disease. […] This review provides a comparative analysis of methodologies and findings to describe how structural biology techniques like X-ray crystallography and cryo-electron microscopy have enabled remarkable discoveries into the structure-function relationship of ACE and ACE2.
33147444 We identified known SARS-CoV-2 host factors, including the receptor ACE2 and protease Cathepsin L. […] We show that HMGB1 regulates ACE2 expression and is critical for entry of SARS-CoV-2, SARS-CoV-1, and NL63.
33147445 In addition, given the key role of the ACE2 receptor in the early stages of viral entry, we show that loss of RAB7A reduces viral entry by sequestering the ACE2 receptor inside cells.
33147451 In addition to an antiviral role for IFNλR1 in the cornea, our results suggest that the human cornea does not support SARS-CoV-2 infection despite expression of ACE2, a SARS-CoV-2 receptor, in the human corneal epithelium.
33148439 Additionally, we tested the association of genetic variants in two key genes related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2), with COVID-19 or any other phenotypes. ), was obtained.
33149112 A cryo-EM structure of the spike bound to Sb23 showed that Sb23 binds competitively in the ACE2 binding site. […] Furthermore, the cryo-EM reconstruction revealed an unusual conformation of the spike where two RBDs are in the ‘up’ ACE2-binding conformation.
33149560 Besides using the angiotensin-converting enzyme (ACE2) receptor as a main gate, the CoV-2 can bind to the glucose-regulating protein 78 (GRP78) receptor to get into the cells to start an infection.
33150674 For a virus to be pathogenic, in addition to its affinity (tropism) for specific tissue(s), host cells must allow viral entry, and discuss the important role played by transmembrane protease, serine 2 (TMPRSS2) and coexpression of both ACE2 and TMPRSS2 in the same cells is important to cause damage. […] Lack of coexpression of ACE2 and TMPRSS2 in the same cells of the kidneys is the limiting factor of SARS-CoV-2 direct effects in the kidney.
33152201 The current SARS-CoV-2, the COVID-19 infectious agent, belongs to a subgroup called betacoronavirus including the SARS-CoV and MERS-CoV responsible for epidemics in 2002 and 2012, respectively.These viruses can also infect the nervous system due to their affinity for the human angiotensin-converting enzyme 2 (ACE2) expressed in neurons and glial cells.
33152616 Spike protein (S2), a envelop glycoprotein aids viral entry into the host cells that corresponds to immunogenic ACE2 receptor binding and represents a potential antiviral drug target.
33153403 : ACE2, angiotensin converting enzyme II; βCoV, betacoronavirus; COVID-19, Coronavirus Disease 2019; CQ, chloroquine; DMV, double-membrane vesicle; GI, gastrointestinal; HCQ, hydroxychloroquine; IL, interleukin; MAP1LC3/LC3, microtubule associated protein 1 light chain 3; MEFs, mouse embryonic fibroblasts; MERS-CoV, Middle East respiratory syndrome coronavirus; MHV, murine hepatitis virus; PE, phosphatidylethanolamine; SARS-CoV, severe acute respiratory syndrome coronavirus; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TMPRSS2, transmembrane serine protease 2; TNF, tumor necrosis factor; WHO, World Health Organization.
33154106 The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus enters host cells via an interaction between its Spike protein and the host cell receptor angiotensin-converting enzyme 2 (ACE2). […] By screening a yeast surface-displayed library of synthetic nanobody sequences, we developed nanobodies that disrupt the interaction between Spike and ACE2. […] Cryo-electron microscopy (cryo-EM) revealed that one nanobody, Nb6, binds Spike in a fully inactive conformation with its receptor binding domains locked into their inaccessible down state, incapable of binding ACE2.
33156843 Analyses of single-cell RNA sequencing data show that co-expression of ACE2 and TMPRSS2 is elevated in absorptive enterocytes from the inflamed ileal tissues of Crohn disease patients compared to uninflamed tissues, revealing shared pathobiology between COVID-19 and inflammatory bowel disease.
33158147 Efficient direct binding to ACE2 was also demonstrated at similar levels in RBD obtained from both methods and from different production lots.
33158276 A detailed dynamic and energetic view of the binding mechanisms underlying virus entry is not fully understood and the consensus around the molecular origins behind binding preferences of SARS-CoV-2 for binding with the angiotensin-converting enzyme 2 (ACE2) host receptor is yet to be established. […] In this work, we performed a comprehensive computational investigation in which sequence analysis and modeling of coevolutionary networks are combined with atomistic molecular simulations and comparative binding free energy analysis of the SARS-CoV and SARS-CoV-2 spike protein receptor binding domains with the ACE2 host receptor. […] Different from other computational studies, we systematically examine the molecular and energetic determinants of the binding mechanisms between SARS-CoV-2 and ACE2 proteins through the lens of coevolution, conformational dynamics, and allosteric interactions that conspire to drive binding interactions and signal transmission. […] The results of this study detailed a binding mechanism in which the energetics of the SARS-CoV-2 association with ACE2 may be determined by cumulative changes of a number of residues distributed across the entire binding interface.
33159236 The broad infective capacity of SARS-CoV-2 is related to the pattern of expression of the viral entry factors ACE2 and TMPRSS2 in human tissues. […] As such, the respiratory and gastrointestinal tracts are at high risk for SARS-CoV-2 infection due to their high expression of ACE2 and TMPRSS2, which explains the clinical phenotype described in the vast majority of infected patients that includes pneumonia and diarrhea. […] Although there is little evidence of the expression of ACE2 and TMPRSS2 in the normal skin, the dermatological findings observed among COVID-19 patients warrants further investigation to delineate the mechanisms of skin affection after SARS-CoV-2 infection.
33159417 To circumvent the devastating pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, a humanized decoy antibody (ACE2-Fc fusion protein) was designed to target the interaction between viral spike protein and its cellular receptor, angiotensin-converting enzyme 2 (ACE2). […] First, we demonstrated that ACE2-Fc could specifically abrogate virus replication by blocking the entry of SARS-CoV-2 spike-expressing pseudotyped virus into both ACE2-expressing lung cells and lung organoids. […] The preservation of peptidase activity also enables ACE2-Fc to reduce the angiotensin II-mediated cytokine cascade. […] Furthermore, this Fc domain of ACE2-Fc was shown to activate NK cell degranulation after co-incubation with Spike-expressing H1975 cells. […] These promising characteristics potentiate the therapeutic prospects of ACE2-Fc as an effective treatment for COVID-19.
33159981 After binding to its receptor angiotensin-converting enzyme 2 (ACE2) on the cell surface, the SARS-CoV-2 is taken up by receptor-mediated endocytosis ending in the acidic endolysosomal compartment.
33160965 The host receptor for severe acute respiratory syndrome coronavirus 2, angiotensin-converting enzyme 2 (ACE2), is highly expressed in small bowel (SB). […] Our aim was to identify factors influencing intestinal ACE2 expression in Crohn’s disease (CD), ulcerative colitis (UC), and non-inflammatory bowel disease (IBD) controls. […] Using bulk RNA sequencing or microarray transcriptomics from tissue samples (4 SB and 2 colonic cohorts; n = 495; n = 387 UC; n = 94 non-IBD), we analyzed the relationship between ACE2 with demographics and disease activity and prognosis. […] We examined the outcome of anti-tumor necrosis factor and anti-interleukin-12/interleukin-23 treatment on SB and colonic ACE2 expression in 3 clinical trials. […] ACE2 levels were consistently reduced in SB CD and elevated in colonic UC compared with non-IBD controls. […] Elevated SB ACE2 was also associated with demographic features (age and elevated body mass index) associated with poor coronavirus disease 2019 outcomes. […] Within CD, SB ACE2 was reduced in patients subsequently developing complicated disease. […] Within UC, colonic ACE2 was elevated in active disease and in patients subsequently requiring anti-tumor necrosis factor rescue therapy. […] SB and colonic ACE2 expression in active CD and UC were restored by anti-cytokine therapy, most notably in responders. […] Reduced SB but elevated colonic ACE2 levels in IBD are associated with inflammation and severe disease, but normalized after anti-cytokine therapy, suggesting compartmentalization of ACE2-related biology in SB and colonic inflammation. […] The restoration of ACE2 expression with anti-cytokine therapy might be important in the context of severe acute respiratory syndrome coronavirus 2 infection and potentially explain reports of reduced morbidity from coronavirus disease 2019 in IBD patients treated with anti-cytokines.
33161277 We highlight two major lines of therapeutic strategies for COVID-19 treatment: 1) repurposing the existing drugs for use in COVID-19 patients, such as antiviral medications (e.g., remdesivir) and immunomodulators (e.g., dexamethasone) which were previously approved for other disease conditions, and 2) novel biological products that are designed to target specific molecules that are involved in SARS-CoV-2 viral entry, including neutralizing antibodies against the spike protein of SARS-CoV-2, such as REGN-COV2 (an antibody cocktail), as well as recombinant human soluble ACE2 protein to counteract SARS-CoV-2 binding to the transmembrane ACE2 receptor in target cells.
33161843 SARS-CoV-2 S protein-containing liposomes were detected in human umbilical vein endothelial cells and human brain microvascular endothelial cells in 3-dimensional middle cerebral artery models but not in monolayer culture consistent with flow dependency of ACE2 expression. […] Brain endothelial cells are susceptible to direct SARS-CoV-2 infection through flow-dependent expression of ACE2.
33163005 Supporting active involvement in the inflammatory risks accompanying COVID-19, DANCR’s decline associated with decrease of the COVID-19-related cellular transcript ACE2 and with sex-related increases in coding transcripts potentiating acetylcholine signaling.
33163958 Its causative virus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), enters human cells through the physical interaction between the receptor-binding domain (RBD) of its spike protein and the human cell receptor ACE2.
33164230 There is growing evidence that androgen-enabled expression of ACE2 receptors and the serine protease TMPRSS2, two permissive elements engaging the SARS-CoV-2 spike protein for infection, may contribute to severe COVID-19 in men.
33164751 Early evidence pointed to angiotensin-converting enzyme 2 (ACE2) as SARS-CoV-2 entry receptor. […] Here, we provide a critical summary of the current knowledge highlighting the limitations and remaining gaps that need to be addressed to fully characterize ACE2 function in SARS-CoV-2 infection and associated pathogenesis. […] We also discuss ACE2 expression and potential role in the context of comorbidities associated with poor COVID-19 outcomes.
33164753 , a gene expressed in alveolar cells and with known functional association with the SARS-CoV-2 receptor ACE2.
33164997 Nasal epithelial cells show the highest expression of angiotensin-converting enzyme 2 (ACE2), the receptor for attachment and entry of SARS-CoV-2 into host cells, among all investigated cells in the respiratory tree. […] Recent studies further suggest that ACE2 may be upregulated by type 1 and downregulated by type 2 inflammatory cytokines in nasal epithelial cells. […] Expression of ACE2 in nasal epithelial cells is influenced by inflammatory endotypes of CRSwNP. […] Type 1 inflammation in nasal tissue may increase the risk of SARS-CoV-2 infection by upregulating ACE2 expression.
33166692 Based on the maximum docked score and minimum atomic contact energy, LPD-12 (-1137.38 kcal) was the appropriate molecule for proper binding with the S-glycoprotein of SARS-CoV-2 and thus significantly interrupted its affinity of binding with angiotensin-converting enzyme-2 (ACE2), which is the only receptor molecule found to be facilitating disease development. […] The results confirmed a strong binding affinity of LPD-12 with ACE2, with a binding free energy of -1621.62 kcal, which could also reciprocally prevent the binding of S-protein. […] It can be concluded that LPD-12 may act as a potential therapeutic drug, by reducing the entry of SARS-CoV-2 to the human cells via the ACE2 receptor and related infections.
33168188 The host-cell receptor angiotensin converting enzyme 2 (ACE2) and the type II transmembrane serine protease (TMPRSS2) are important for viral cell entry. […] It is unclear whether obesity alters expression of Ace2 and Tmprss2 in the lower respiratory tract. […] Here, we show that: 1) Ace2 expression is elevated in the lung and trachea of diet-induced obese male mice and reduced in the esophagus of obese female mice relative to lean controls; 2) Tmprss2 expression is increased in the trachea of obese male mice but reduced in the lung and elevated in the trachea of obese female mice relative to lean controls; 3) in chow-fed lean mice, females have higher expression of Ace2 in the lung and esophagus as well as higher Tmprss2 expression in the lung but lower expression in the trachea compared to males; and 4) in diet-induced obese mice, males have higher expression of Ace2 in the trachea and higher expression of Tmprss2 in the lung compared to females, whereas females have higher expression of Tmprss2 in the trachea relative to males. […] Our data indicate diet- and sex-dependent modulation of Ace2 and Tmprss2 expression in the lower respiratory tract and esophagus.
33169110 Further angiotensin converting enzyme 2 (ACE2) the known receptor for the virus is extensively expressed in these cells.
33170175 This virus is able to attack the cells of the airway epithelium by binding to the transmembrane angiotensin I converting enzyme 2 (ACE2). […] The spray contains hydroxytyrosol for its anti-viral, anti-inflammatory and anti-oxidant properties, and α-cyclodextrin for its ability to deplete sphingolipids, that form the lipid rafts where ACE2 localizes.
33170176 In addition, we identified possible interactions among hydroxytyrosol and alpha-cyclodextrin with the protein Spike and the human proteins ACE2 and TMPRSS2.
33170317 Here, we focus our attention on ACE2, a primary receptor of SARS-CoV-2. […] Particular attention will be given to how the ACE2 soluble form can have a great impact on disease progression and thus be used in a potential therapeutic strategy. […] Furthermore, we will discuss repercussions that SARS-CoV-2/ACE2 binding has on the renin-angiotensin system and beyond. […] Indeed, although mostly neglected, ACE2 can also act on [des-Arg 937]-bradykinin of the kinin-kallikrein system regulating coagulation and inflammation. […] Thorough comprehension of the role that ACE2 plays in different pathways will be the key to assess the impact that SARS-CoV-2/ACE2 binding has on organismal physiology and will help us to find better therapies and diagnostic tools.
33171852 The virus SARS-CoV-2 employs the Angiotensin-converting enzyme 2 (ACE2), a component of the RAAS (Renin-Angiotensin-Aldosterone System) system, as a receptor for entry into the cells. […] We also examined ACE2 modulation in sight of SARS2-Cov infection prevention.
33172369 It was first reported in Wuhan, China in December, 2019 and despite the tremendous efforts to control the disease, it has now spread almost all over the world.The interaction of SARS-CoV-2spike protein and its acceptor protein ACE2 is an important issue in determining viralhost range and cross-species infection, while the binding capacity of spike protein toACE2 of different species is unknown. […] We evaluated the receptor-utilizing capability of ACE2sfrom various species by sequence alignment,phylogenetic clustering and protein-ligand interaction studies with the currently knownACE2s utilized by SARS-CoV-2. […] In-silico study predicted that SARS-CoV-2 tends to utilize ACE2s ofvarious animal species with varied possible interactions and theprobability ofthe receptor utilization will be greater in horse and poor in chicken followed by ruminants. […] Present studypredicted that SARS-CoV-2 tends to utilize ACE2s ofvarious livestock and poultry species with greater probability in equine and poor in chicken.
33172372 SARS-CoV-2 has been shown to bind the host cell ACE2 receptor through its spike protein receptor binding domain (RBD), required for its entry into the host cells. […] We have screened phytocompounds from a medicinal herb, Tinospora cordifolia, for their capacities to interrupt the viral RBD and host ACE2 interactions. […] We employed molecular docking to screen phytocompounds in T. cordifolia against the ACE2-RBD complex, performed molecular dynamics (MD) simulation, and estimated the electrostatic component of binding free energy. […] ‘Tinocordiside’ docked very well at the center of the interface of ACE2-RBD complex, and was found to be well stabilized during MD simulation. […] Tinocordiside incorporation significantly decreased electrostatic component of binding free energies of ACE2-RBD complex (23.5 and 17.10 kcal/mol in the trajectories without or with the ligand, respectively). […] It indicates that such an interruption of electrostatic interactions between the RBD and ACE2, and the increase in global flexibility of the complex, would weaken or block SARS-CoV-2 entry and its subsequent infectivity.
33173010 While ACE2 has been identified as the viral receptor, cellular polysaccharides have also been implicated in virus entry.
33173592 A recent experimental study found that the binding affinity between the cellular receptor human angiotensin-converting enzyme 2 (ACE2) and receptor-binding domain (RBD) in the spike (S) protein of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is more than tenfold higher than that of the original severe acute respiratory syndrome coronavirus (SARS-CoV). […] Understanding the physical mechanism responsible for the outstanding affinity between the SARS-CoV-2 S and ACE2 is an “urgent challenge” for developing blockers, vaccines, and therapeutic antibodies against the coronavirus disease 2019 (COVID-19) pandemic. […] Taking into account the mechanisms of hydrophobic interaction, hydration shell, surface tension, and the shielding effect of water molecules, this study reveals a hydrophobic-interaction-based mechanism by means of which SARS-CoV-2 S and ACE2 bind together in an aqueous environment. […] The hydrophobic interaction between the SARS-CoV-2 S and ACE2 protein is found to be significantly greater than that between SARS-CoV S and ACE2. […] At the docking site, the hydrophobic portions of the hydrophilic side chains of SARS-CoV-2 S are found to be involved in the hydrophobic interaction between SARS-CoV-2 S and ACE2.
33173846 Here, a computational strategy is developed to adaptively evolve peptides that could selectively inhibit mutating S protein receptor binding domains (RBDs) of different SARS-CoV-2 viral strains from binding to their human host receptor, angiotensin-converting enzyme 2 (ACE2). […] Starting from suitable peptide templates, based on selected ACE2 segments (natural RBD binder), the templates are gradually modified by random mutations, while retaining those mutations that maximize their RBD-binding free energies.
33174446 The dangerous combination of enhanced SARS-CoV-2 attachment receptor protein ACE2 along with an increase in endocytic vacuoles will enable viral attachment, entry, and replication. […] The objective of the study was to identify the presence of SARS-CoV-2 host attachment receptor angiotensin-converting enzyme-2 (ACE2) along with endocytic vacuoles, early endosome antigen-1 (EEA1), late endosome marker RAB7, cathepsin-L, and lysosomal associated membrane protein-1 (LAMP-1) as lysosome markers in the airways of smokers and COPD patients. […] Immunostaining for ACE2, EEA1, RAB7, and cathepsin-L was done. […] A comparative description for ACE2, EEA1, RAB7, and cathepsin-L expression pattern is provided for the patient groups. […] The active presence of ACE2 protein along with endocytic vacuoles such as early/late endosomes and lysosomes in the small airways of smokers and COPD patients provides evidence that these patient groups could be more susceptible to COVID-19.
33174447 These proteins include the viral receptor, angiotensin-converting enzyme 2 (ACE2), and the proteases, transmembrane serine protease 2 (TMPRSS2) and furin. […] During cellular differentiation, we measured the expression of ACE2, TMPRSS2, and furin over progressive ALI days by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blot, and immunofluorescence staining. […] Like ACE2, TMPRSS2 and furin proteins are localized in differentiated ciliated cells, as confirmed by immunofluorescence staining.
33174669 In humans, a protein-protein interaction (PPI) between the SARS CoV-2 receptor-binding domain (RBD) and the extracellular peptidase domain of ACE2 on the surface of cells in the lower respiratory tract is an initial step in the entry pathway. […] Inhibition of the SARS CoV-2 RBD/ACE2 PPI is currently being evaluated as a target for therapeutic and/or prophylactic intervention. […] Employing multiple computational platforms, we predicted “hot-spot” residues in a positive-control PPI (PMI/MDM2) and the CoV-2 RBD/ACE2 complex. […] Computational alanine scanning mutagenesis was performed to predict changes in Gibbs’ free energy that are associated with mutating residues at the positive control (PMI/MDM2) or SARS RBD/ACE2 binding interface to alanine. […] Additionally, we used the Adaptive Poisson-Boltzmann Solver to calculate macromolecular electrostatic surfaces at the interface of the positive-control PPI and SARS CoV-2/ACE2 PPI. […] Finally, a comparative analysis of hot-spot residues for SARS-CoV and SARS-CoV-2, in complex with ACE2, is provided. […] Collectively, this study illuminates predicted hot-spot residues, and clusters, at the SARS CoV-2 RBD/ACE2 binding interface, potentially guiding the development of reagents capable of disrupting this complex and halting COVID-19.
33175236 A recent publication reported an experimental 3D complex structure of the S protein of SARS-CoV-2 showed that the ectodomain of the SARS-CoV-2 S protein binds to the peptidase domain (PD) of human ACE2 with a dissociation constant (Kd) of ~ 15 nM. […] In this study, we focused on inhibitors for ACE2: S protein complex using virtual screening and inhibition studies through molecular docking for over 200,000 natural compounds. […] We found two natural origin inhibitors for the S protein: human ACE2 complex (Andrographolide and Pterostilbene) which displayed better inhibition potential for ACE2 receptor and its binding with the S protein of SARS-CoV-2. […] Supplementary experimental studies need to be carried forward to corroborate the viability of these two new inhibitors for ACE2: S protein complex so as to curb down COVID-19.
33175551 Given that binding to ACE2 proteins is the first step for the coronaviruses to invade host cells, we propose a computational pipeline to identify potential intermediate hosts of SARS-CoV-2 by modeling the binding affinity between the Spike receptor-binding domain (RBD) and host ACE2. […] Using this pipeline, we systematically examined 285 ACE2 variants from mammals, birds, fish, reptiles, and amphibians, and found that the binding energies calculated for the modeled Spike-RBD/ACE2 complex structures correlated closely with the effectiveness of animal infection as determined by multiple experimental data sets.
33175635 In December 2019, a highly pathogenic coronavirus called SARS-CoV-2 (formerly identified as 2019-nCoV) appeared in Wuhan, China, and has since been spreading rapidly around the world. we reviewed the neurological manifestations of this infection and the potential of ACE2 in the nervous system. […] The spike protein of the virus and the angiotensin-converting enzyme 2 (ACE2) lead to the presence of both SARS-CoV and SARS-CoV-2 in the cells and, subsequently, decreased ACE2 expression. […] The therapeutic possibilities of ACE2 antibody, ACE2-derived peptides, and small molecule blockers of ACE2 include a receptor-binding domain blocking approach. […] Hence, future studies of ACE2 may be very helpful in discovering a therapy for SARS-CoV-2.
33177594 SARS-CoV-2, the pathogenic agent of COVID-19, employs angiotensin converting enzyme-2 (ACE2) as its cell entry receptor. […] Physiologically, ACE2 plays a role in the regulation of three systems that could potentially be involved in the pathogenesis of severe COVID-19: the kinin-kallikrein system, resulting in acute lung inflammatory edema; the renin-angiotensin system, promoting cardiovascular instability; and the coagulation system, leading to thromboembolism. […] Here we assembled a healthy human lung cell atlas meta-analysis with ~ 130,000 public single-cell transcriptomes and show that key elements of the bradykinin, angiotensin and coagulation systems are co-expressed with ACE2 in alveolar cells and associated with their differentiation dynamics, which could explain how changes in ACE2 promoted by SARS-CoV-2 cell entry result in the development of the three most severe clinical components of COVID-19.
33177848 Based on previously published evidence, ACE2 and TMPRSS2 are both pivotal entry molecules that enable cellular infection by SARS-CoV-2. […] We investigated the expression pattern of ACE2 and TMPRSS2 in major organs in the human body, especially in specific disease conditions. […] Multiple sequence alignment of ACE2 in different species was used to explain animal susceptibility. […] Moreover, the cell-specific expression patterns of ACE2 and cytokine receptors in the urinary tract were assessed using single-cell RNA sequencing (scRNA-seq). […] Additional biological relevance was determined through Gene Set Enrichment Analysis (GSEA) using an ACE2-specific signature. […] Our results revealed that ACE2 and TMPRSS2 were highly expressed in genitourinary organs. […] ACE2 was highly and significantly expressed in the kidney among individuals with chronic kidney diseases or diabetic nephropathy. […] In single cells, ACE2 was primarily enriched in gametocytes in the testis and renal proximal tubules.
33178900 The binding of the SARS-CoV-2 virus to the angiotensin-converting enzyme 2 (ACE2) and its intake by the host cell is a necessary step for infection. […] ACE2 has garnered widespread therapeutic possibility as it is entry/interactive point for SARS-CoV-2, responsible for coronavirus disease 2019 (COVID-19) pandemic and providing a critical regulator for immune modulation in various disease. […] Therefore, in light of the ACE-2 as an important contributor of COVID-19 global, we analyzed correlation between ACE2 and tumor immune infiltration (TIL) level and the type markers of immune cells were investigated in breast cancer subtypes by using TIMER database. […] Our findings shed light on the immunomodulatory role of ACE2 in the luminal A subtype which may play crucial role in imparting therapeutic resistance in this cancer subtype.
33179852 ACE2 is the critical cell surface receptor for SARS-CoV-2. […] Here, we investigated additive effect of combination therapy using remdesivir with recombinant soluble ACE2 (high/low dose) on Vero E6 and kidney organoids, targeting two different modalities of SARS-CoV-2 life cycle: cell entry via its receptor ACE2 and intracellular viral RNA replication.
33181224 There is increasing evidence that ACE2 gene polymorphism can modulate the interaction between ACE2 and the SARS-CoV-2 spike protein affecting the viral entry into the host cell, and/or contribute to lung and systemic damage in COVID-19. […] Here we used in silico molecular docking to predict the effects of ACE2 missense variants on the interaction with the spike protein of SARS-CoV-2. […] HDOCK and FireDock simulations identified 6 ACE2 missense variants (I21T, A25T, K26R, E37K, T55A, E75G) with higher affinity for SARS-CoV-2 Spike protein receptor binding domain (RBD) with respect to wild type ACE2, and 11 variants (I21V, E23K, K26E, T27A, E35K, S43R, Y50F, N51D, N58H, K68E, M82I) with lower affinity. […] This result supports the hypothesis that ACE2 genetic background may represent the first “genetic gateway” during the disease progression.
33182073 The ninth section describes about transgenic humane ACE2 (hACE2) receptor expressing mice to study immunity, drugs, and vaccines.
33183854 Steady knowledge on the pathogenesis of the virus has revealed certain consistent features specific to the disease which includes massive destruction of the lung due to the presence of excessive angiotensin-converting enzyme receptors (ACE2) which are essential for the viral entry inside the host.
33183974 The angiotensin-converting enzyme 2 (ACE2), which acts as the SARS-CoV-2 receptor, is present in endothelial cells and has been noted within the human placenta. […] In this report, we highlight physiological and immune/inflammatory considerations that may explain the susceptibility and disease pathology in response to SARS CoV-2 during pregnancy, explore testing considerations in asymptomatic individuals, discuss the potential role and of placental ACE2 receptor in the pathogenesis of COVID-19 in pregnancy and in pregnancy outcomes, and finally share our perspective with respect to an urgently needed change concerning involvement of pregnant women in research addressing COVID-19.
33184236 Infection of human angiotensin-converting enzyme 2 (ACE2) transgenic mice and Syrian hamsters with both viruses resulted in similar viral titers in respiratory tissues and pulmonary disease.
33184246 It binds nicely at the S-protein-ACE2 interface by making substantial π-π interactions with Tyr505 in the ‘Site 1’ hook region of RBD and hydrophilic interactions with Glu406, Ser494, and Thr500.
33184506 Recently, angiotensin-converting enzyme 2 (ACE2) has been shown to be a functional receptor for virus entry into host target cells. […] The upregulation of ACE2 in patients with comorbidities may represent a propensity for increased viral load and spreading of infection to extrapulmonary tissues.
33184600 Virus enters cell through spike glycoprotein fusion with ACE2 (Angiotensin-Converting Enzyme 2) human receptor. […] Also, virus entry can be prevented by blocking ACE2 thus, ACE2 can be considered potential target for therapeutics. […] In present study, we retrieved sequence of 70 peptides from Antiviral Peptide Database (AVPdb), modelled them using 3D structure predicting web tool and docked them with receptor binding domain (RBD) of spike protein and human host receptor ACE2 using peptide-protein docking. […] It was observed that peptides have more affinity towards ACE2 in comparison with spike RBD. […] Interestingly it was noticed that most of the peptides bind to RBM (residue binding motif) which is responsible for ACE2 binding at the interface of RBD while, for ACE2, peptides prefer to bind the core cavity rather than RBD binding interface. […] To further investigate how peptides at the interface of RBD or ACE2 alter the binding between RBD and ACE2, protein-protein docking of RBD and ACE2 with and without peptides was performed. […] Peptides, AVP0671 at RBD and AVP1244 at ACE2 interfaces significantly reduce the binding affinity and change the orientation of RBD and ACE2 binding.
33185582 Angiotensin-converting enzyme 2 (ACE2) is a major receptor for some coronavirus infection, including SARS-COV-2, but is also a crucial determinant in anti-inflammation processes during the renin-angiotensin system (RAS) functioning - converting angiotensin II to angiotensin 1-7. […] The decline in ACE2 expression that occurs with aging has been associated to the higher morbidity and mortality rates in older adults.
33186186 Angiotensin-converting enzyme 2 (ACE2) is the receptor for the attachment and entry of SARS-CoV-2 into the host cells that is upregulated by Th1-mediated responses. […] In asthmatics, ACE2 gene expression is generally reduced and recent studies have shown a negative correlation between the levels of Th2 cytokines including IL-4, IL-5, and IL-13 in airway epithelial cells and other type 2 biomarkers with ACE2 expression. […] Expression of ACE2 in airway epithelial cells in SARS-COV-2 is influenced by inflammatory profile.
33186231 The spike glycoprotein plays a critical role in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by recognizing the angiotensin converting enzyme 2 (ACE2) receptor and mediating fusion of the viral envelope with the cell membrane. […] SARS-CoV-2 spike glycoprotein, similar to those of SARS-CoV and Middle East respiratory syndrome coronavirus, spontaneously samples different prefusion states with the receptor-binding domain (RBD) adopting ‘up’ or ‘down’ conformations, and the RBD ‘down’ to ‘up’ conformational change is required for ACE2 binding. […] Interactions between SARS-CoV-2 RBD and ACE2 were elucidated at atomic resolution using high-resolution crystal structures.
33186749 Immunostaining for viral entry receptor ACE2 and SARS-CoV-2 spike protein priming protease TMPRSS2 showed broad expression in the gastrointestinal tract with highest levels in the intestine, the latter faithfully recapitulated by PSC-HIOs. […] However, SARS-CoV-2 spared goblet cells lacking ACE2 expression.
33187074 Angiotensin-converting enzyme 2 (ACE2) is the receptor that allows the entry of these two viruses into host cells, a key step in the life cycle of the pathogens. […] The characterization of the interactions of ACE2 with the viral spike glycoproteins and structural studies of the ACE2-binding-induced conformational changes in the viral spike glycoproteins have furthered our understanding of the entry processes of these two viruses, and these studies provide useful information that will facilitate the development of antiviral agents and vaccines to control the diseases.
33187644 Of particularly interest, the antibodies against domain of the Spike that interacts with the cellular receptor ACE2, known as the receptor binding domain (RBD), are present in most infected individuals and are block viral entry and infectivity.
33187978 Using organotypic 3D cultures of primary human liver cells, we demonstrate that interferon-α2 increases ACE2 expression and SARS-CoV-2 infectivity in parenchymal cells by greater than fivefold.
33188207 Here, we report a monoclonal antibody (mAb), MW05, with SARS-CoV-2 neutralizing activity by disrupting the interaction of receptor binding domain (RBD) with angiotensin-converting enzyme 2 (ACE2) receptor.
33188364 Angiotensin-converting enzyme 2 (ACE2), which is part of the renin-angiotensin-aldosterone system (RAAS), is the main entry receptor for SARS-CoV-2; although dipeptidyl peptidase 4 (DPP4) might also act as a binding target.
33188579 Angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2) are the main host cell factors for the Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) entry but so far it is unclear if human MSCs express or do not these two proteins. […] To elucidate these important aspects, we evaluated if human MSCs from both fetal and adult tissues constitutively express ACE2 and TMPRSS2 and, most importantly, if they can be infected by SARS-CoV-2. […] ACE2 and TMPRSS2 were expressed by the SARS-CoV-2-permissive human pulmonary Calu-3 cell line but not by all the MSCs tested.
33189452 Interestingly, both events have been reported in patients with COVID-19, in whom hyperinsulinemia increases the surface expression of ACE2 through a diminution of ADAMTS17 activity; whereas hyperglycemia induces higher expression of ACE2 in different tissues, including microvascular endothelial cells from the pancreatic islets, favoring chronic hyperglycemia and affecting the release of insulin.
33189453 Currently, SARS- CoV-2 is thought to evade innate antiviral immunity, undergo endocytosis, and fuse with the host cell membrane by exploiting ACE2 receptors and the protease TMMPRSS2, with cathepsin B/L as alternative protease, for entry into the epithelial cells of tissues vulnerable to developing coronavirus disease 2019 (COVID-19) symptoms. […] Here, I will rationalize the possibility that other host molecules-i.e., sugar molecules and the sialic acidsN-glycolylneuraminic acid, N-acetylneuraminic acid, and their derivates could be viable candidates for the use as virus receptors by SARS-CoV-2 and/or serve as determinants for the adherence on ACE2 of SARS-CoV-2.
33189680 Although numerous drug and vaccine development efforts are underway, there are many outstanding questions on the mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral association to angiotensin-converting enzyme 2 (ACE2), its main host receptor, and host cell entry. […] Here, we perform explicitly solvated, all-atom, molecular dynamics simulations of the glycosylated, full-length, membrane-bound ACE2 receptor in both an apo and spike RBD-bound state to probe the intrinsic dynamics of the ACE2 receptor in the context of the cell surface. […] A large degree of fluctuation in the full-length structure is observed, indicating hinge bending motions at the linker region connecting the head to the transmembrane helix while still not disrupting the ACE2 homodimer or ACE2-RBD interfaces. […] This flexibility translates into an ensemble of ACE2 homodimer conformations that could sterically accommodate binding of the spike trimer to more than one ACE2 homodimer and suggests a mechanical contribution of the host receptor toward the large spike conformational changes required for cell fusion. […] This work presents further structural and functional insights into the role of ACE2 in viral infection that can potentially be exploited for the rational design of effective SARS-CoV-2 therapeutics.
33189768 Here, we summarize the current status of peptides inhibiting SARS-CoV-2 entry and outline the strategies used to design peptides targeting the ACE2 receptor or the viral spike protein and its activating proteases furin, transmembrane serine protease 2 (TMPRSS2), or cathepsin L.
33190011 , spike protein, and ACE2 receptor act as appropriate targets for the development of therapeutics against SARS-CoV-2.
33190150 Expression quantitative trait loci analysis also revealed a link between SMN1 and ACE2, despite low-confidence protein-protein interactions as suggested by STRING.
33191068 The top 34 compounds in the Chinese medicine-compound-target network were docked with SARS-CoV-2 3CL enzyme and SARS–CoV–2 RNA-dependent RNA polymerase (RdRp) and then the 13 compounds with lowest affinity score were docked with angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 Spike protein and interleukin 6 to explore its interaction mechanism. […] In addition, the SPR experiments revealed that the quercetin and isoquercitrin were combined with SARS-CoV-2 Spike protein rather than Angiotensin-converting enzyme 2, while astragaloside IV and rutin were combined with ACE2 rather than SARS-CoV-2 Spike protein.
33191178 We investigated the neutralizing effect of anti-spike-S1 IgYs on the SARS-CoV-2 pseudovirus, as well as its inhibitory effect on the binding of the coronavirus spike protein mutants to human ACE2.
33191600 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, enters human cells by binding of its viral protein to the aminopeptidase angiotensin-converting enzyme 2 (ACE2).
33192492 For instance, the mechanisms by which COVID-19 may contribute to hemorrhagic stroke may include both depletion of angiotensin converting enzyme 2 (ACE2) receptor and overactive immune response.
33193019 The reduction of the angiotensin-converting enzyme II (ACE2) caused by SARS-CoV-2 binding to the ACE2 receptor can lead to abnormally elevated blood pressure and increase the risk of hemorrhagic stroke.
33193331 SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) receptor and mainly spreads through the respiratory tract, which it then uses to reach several organs.
33193639 Previous reports have indicated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV are highly homologous and both use angiotensin-converting enzyme 2 (ACE2) as the receptor to enter cells, and SARS-CoV infection reduces the ACE2 expression in the lung. […] Therefore, the analysis of genes co-expressed with ACE2 in the lung may uncover the underlying mechanism of COVID-19. […] Furthermore, we identified genes co-expressed with ACE2 in healthy lung samples and analyzed the significant genes. […] Additionally, to identify several candidate drugs for the treatment of COVID-19, we queried Cmap using DEGs and genes co-expressed with ACE2. […] Genes positively correlated with ACE2 are related to immune defense and those negatively correlated are enriched in synaptic transmission functions. […] Furthermore, ACE2 may not only mediate viral entrance, but also play an important role in immune defense.
33193684 The interaction of SARS-CoV-2 spike protein and its acceptor protein ACE2 is an important issue in determining viral host range and cross-species infection, while the binding capacity of Spike protein to ACE2 of different species is unknown. […] Here, we used the atomic structure model of SARS-CoV-2 and human ACE2 to assess the receptor utilization capacity of ACE2s from 10 kinds of animals. […] Furthermore, based on ACE2(cats)-SARS-CoV-2-RBD model, through high-throughput screening methods using a pool of 30,000 small molecules, eight compounds were selected for binding free energy calculations. […] All the eight compounds can effectively interfere with the binding of ACE2 and Spike protein, especially Nelfinavir, providing drug candidates for the treatment and prevention of SARS-CoV-2, suggesting further assessment of the anti-SARS-CoV-2 activity of these compounds in cell culture.
33193695 Ribavirin was predicted to be the best small molecular drug, with a higher molecular binding energy of -6.39 kcal/mol with human angiotensin-converting enzyme 2 (ACE2), followed by remdesivir (-7.4 kcal/mol), mycophenolic acid (-5.35 kcal/mol), and chloroquine (-6.29 kcal/mol). […] In addition, for the first time, our results suggested several antiviral drugs, such as FK506, with molecular binding energies of -11.06 and -10.1 kcal/mol with ACE2 and the spike protein, respectively, could be potentially used to prevent SARS-CoV-2 and remains to further validation.
33194061 Further logistic regression analysis showed that TPNT was highly associated with serum TG level and hypertension that were related to the expression of ACE2, the targeting protein for the invasion of SARS-CoV-2.
33194122 SARS-CoV2 expresses high affinity to human ACE2 receptors, including within the gastrointestinal tract.
33195060 Naturally occurring and clinically available triterpenoids such as glycyrrhetinic and oleanolic acids, as well as primary and secondary bile acids and their amidated derivatives such as glyco-ursodeoxycholic acid and semi-synthetic derivatives such as obeticholic acid reduces the RBD/ACE2 binding.
33195212 To explore the susceptibility factors of cancer patients, we assessed the expression of ACE2, TMPRSS2, and the endocytic regulator AAK1 in lung adenocarcinoma (LUAD) patients and explored their effects on immune infiltration. […] We found that the expression of ACE2 and TMPRSS2 in LUAD patients was significantly increased, which may explain why LUAD patients are susceptible to SARS-CoV-2, and the patients with high-expression genes presented increased infiltration of immune cells such as B cells and CD4 T cells.
33195400 Tracing back the knowledge acquired from SERS and MERS infections, clinical evidence suggested similar host immune reactions and host ACE2 receptor-derived invasion by SARS-CoV-2.
33195415 On the other hand, ACE2, a receptor for the SARS-CoV-2 virus, was found to be aberrantly expressed in many tumors. […] However, the characterization of aberrant ACE2 expression in malignant tumors has not been elucidated. […] Here, we conducted a systematic analysis of the ACE2 expression profile across 31 types of tumors. […] Distribution of ACE2 expression was analyzed using the GTEx, CCLE, TCGA pan-cancer databases. […] We evaluated the effect of ACE2 on clinical prognosis using the Kaplan-Meier survival plot and COX regression analysis. […] Correlation between ACE2 and immune infiltration levels was investigated in various cancer types. […] Additionally, the correlation between ACE2 and immune neoantigen, TMB, microsatellite instability, Mismatch Repair Genes (MMRs), HLA gene members, and DNA Methyltransferase (DNMT) was investigated. […] The frequency of ACE2 gene mutation in various tumors was analyzed. […] In normal tissues, ACE2 was highly expressed in almost all 31 organs tested. […] In cancer cell lines, the expression level of ACE2 was low to medium. […] Although aberrant expression was observed in most cancer types, high expression of ACE2 was not linked to OS, DFS, RFS, and DFI in most tumors in TCGA pan-cancer data. […] We found that ACE2 expression was significantly correlated with the infiltrating levels of macrophages and dendritic cells, CD4+ T cells, CD8+ T cells, and B cells in multiple tumors. […] A positive correlation between ACE2 expression and immune neoantigen, TMB, and microsatellite instability was found in multiple cancers. […] GSEA analysis which was carried out to determine the effect of ACE2 on tumors indicated that several cancer-associated pathways and immune-related pathways were hyperactivated in the high ACE2 expression group of most tumors. […] These findings suggest that ACE2 is not correlated with prognosis in most cancer types. […] However, elevated ACE2 is significantly correlated with immune infiltrating levels, including those of CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and DCs in multiple cancers, especially in lung and breast cancer patients. […] These findings suggest that ACE2 may affect the tumor environment in cancer patients with COVID-19.
33195427 Spike protein is the outermost structural protein of the SARS-CoV-2 virus which interacts with the Angiotensin Converting Enzyme 2 (ACE2), a human receptor, and enters the respiratory system. […] Nevertheless, the closed conformation disables its ability to bind to ACE2, due to the burying of its receptor binding residues.
33195436 Also, ACE2 expression is regulated post-translationally by glycosylation, phosphorylation, and shedding from the plasma membrane. […] ACE2 protein is ubiquitous across mammalian tissues, prominently in the cardiovascular system, kidney, and intestine. […] ACE2 expression in the respiratory tract is of particular interest, in light of the discovery that ACE2 serves as the initial cellular target of severe acute respiratory syndrome (SARS)-coronaviruses, including the recent SARS-CoV2, responsible of the COronaVIrus Disease 2019 (COVID-19). […] Since the onset of the COVID-19 pandemic, an intense effort has been made to elucidate the biochemical determinants of SARS-CoV2-ACE2 interaction. […] It has been determined that SARS-CoV2 engages with ACE2 through its spike (S) protein, which consists of two subunits: S1, that mediates binding to the host receptor; S2, that induces fusion of the viral envelope with the host cell membrane and delivery of the viral genome. […] Owing to the role of ACE2 in SARS-CoV2 pathogenicity, it has been speculated that medical conditions, i.e., hypertension, and/or drugs, i.e., ACE inhibitors and angiotensin receptor blockers, known to influence ACE2 density could alter the fate of SARS-CoV-2 infection. […] An interesting observation is, however that, upon infection, ACE2 activity is reduced either by downregulation or by shedding. […] As evidence accumulates, ACE2 appears a druggable target in the attempt to limit virus entry and replication. […] Strategies aimed at blocking ACE2 with antibodies, small molecules or peptides, or at neutralizing the virus by competitive binding with exogenously administered ACE2, are currently under investigations. […] In this review, we will present an overview of the state-of-the-art knowledge on ACE2 biochemistry and pathophysiology, outlining open issues in the context of COVID-19 disease and potential experimental and clinical developments.
33195477 The SARS-Cov2 virus, responsible for COVID-19, achieves cell entry through an S (spike) high-affinity protein binding to the catalytic domain of the angiotensin-converting enzyme 2 (ACE2), a negative regulator of the RAS pathway. […] Therefore, it is crucial to examine the relationship between small resistance artery disease, ACE2, and PAH, to understand COVID-19 morbidity and mortality. […] The scope of the present review is to briefly summarize available knowledge on the role of small resistance artery disease and ACE2 in PAH, and critically discuss their clinical relevance in the context of cardiovascular pathology associated to COVID-19.
33195813 The risk of transmission via the ocular surface remains likely low, though it is inarguably present based on preliminary finding of viral load in ocular samples and expression of ACE2 on the ocular surface.
33196003 Spike proteins are the most important proteins found on its capsule using the host’s ACE2 receptors to invade respiratory cells.
33196058 SARS-CoV-2 appears to infect cells by first binding and priming its viral-spike proteins with membrane-associated angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). […] Through the coordinated actions of ACE2 and TMPRSS2, SARS-CoV-2 spike proteins fuse with plasma membranes and ultimately the virus enters cells. […] ACE2 is integral to the renin-angiotensin-aldosterone system (RAAS), and SARS-CoV-2 down-regulates protein expression levels of ACE2.
33197855 Common proteins included the SARS-CoV-2 entry receptor ACE2 and ENDOU, a placental endoribonuclease homologous to Nsp15, a protein produced by the virus to escape host immunity. […] Remarkably, placental ENDOU mRNA expression far exceeded that of ACE2.
33197881 SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) uses the angiotensin-converting enzyme 2 (ACE2) receptor for infecting and spreading in humans. […] Studies have shown that the widespread expression of ACE2 in human tissues may be associated with organ function damage (e.g., lung, kidney, and stomach) in patients with coronavirus disease 2019 (COVID-19). […] However, in neurodegenerative diseases, whose pathogenesis is closely related to advanced age, ACE2 plays a neurotrophic and protective role by activating the ACE2/Ang-(1-7)/Mas axis, thus inhibiting cognitive impairment. […] Therefore, during the COVID-19 pandemic, it is crucial to understand the role of ACE2 in neurodegenerative diseases. […] In this paper, we review the relationship between COVID-19, neurodegenerative diseases, and ACE2, as well as provide recommendations for the protection of elderly patients with neurodegenerative diseases during the COVID-19 pandemic.
33199671 We also identified miRNAs that bind to receptor proteins, such as ACE2, ADAM17, and TMPRSS2, which are important for understanding the infection mechanism of SARS-CoV-2.
33200026 Here, we identified puerarin (PubChem CID: 5281807), quercetin (PubChem CID: 5280343) and kaempferol (PubChem CID: 5280863) as potential compounds with binding activity to ACE2 by using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). […] Molecular docking analysis showed that puerarin and quercetin exhibit good binding affinity to ACE2, which was validated by surface plasmon resonance (SPR) assay. […] Furthermore, SPR-based competition assay revealed that puerarin and quercetin could significantly affect the binding of viral S-protein to ACE2 receptor.
33203141 The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) determines the angiotensin converting enzyme 2 (ACE2) down-regulation and related decrease in angiotensin II degradation. […] Thus, NEP/angiotensin receptor type 1 (AT1R) inhibitor sacubitril/valsartan (SAC/VAL) may increase levels of these molecules and block AT1Rs required for ACE2 endocytosis in SARS-CoV-2 infection.
33203679 A central mechanism for COVID-19 pathophysiology has been proposed: imbalance of angiotensin converting enzymes (ACE)1 and ACE2 (ACE2 being the severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] virus “receptor”) that results in tissue injury from angiotensin II (Ang II)-mediated signaling. […] Other approaches related to the RAS pathway might be considered, for example, inhalational administration of ACEIs/ARBs (to deliver drugs directly to the lungs) and use of compounds with other actions (e.g., activation of ACE2, agonism of MAS1 receptors, β-arrestin-based Angiotensin receptor agonists, and administration of soluble ACE2 or ACE2 peptides).
33203793 ACE2 was observed as the cell surface receptor of the SARS-CoV-2 virus. […] Interestingly, we also found ACE2 positivity inside the cell nucleus. […] The ACE2 levels changed during cell differentiation and aging and varied in distinct cell types. […] We observed ACE2 depletion in the aortas of aging female mice, similarly, the aging caused ACE2 decrease in the kidneys. […] Compared with that in the heart, brain and kidneys, the ACE2 level was the lowest in the mouse lungs. […] In mice exposed to nicotine, ACE2 was not changed in olfactory bulbs but in the lungs, ACE2 was upregulated in females and downregulated in males. […] These observations indicate the distinct gender-dependent properties of ACE2. […] Differentiation into enterocytes, and cardiomyocytes, caused ACE2 depletion. […] In contrast, vitamin D2 decreased the renin level while ACE2 was upregulated. […] Together, the ACE2 level is high in non-differentiated cells. […] Mostly, downregulation of ACE2 is accompanied by renin upregulation. […] Thus, the pathophysiology of COVID-19 disease should be further studied not only by considering the ACE2 level but also the whole renin-angiotensin system.
33204291 Radix et Rhizoma, quercetin, glabridin, and gallic acid present in the herbal formulas and medicines were found to alter ACE2 expression. […] Quercetin, glabridin, and gallic acid, the active components of recommended TCM formulas and medicines, can inhibit COVID-19 by downregulating ACE2.
33204713 Angiotensin-converting enzyme 2 (ACE2), the major receptor of SARS-CoV-2, is one of the major members of the renin-angiotensin system (RAS). […] In this review, we aimed to summarize the crucial roles of ACE2 in the pathogenesis of COVID-19, followed by illustrating potential treatment options relating to ACE2 and the RAS.
33205194 The SARS-CoV-2 virus enters the host cells by binding to the angiotensin-converting enzyme 2 (ACE2). […] Here, we report that the ACE2 protein is expressed in both endometrial epithelial and stromal cells in the proliferative phase of the menstrual cycle, and the expression increases in stromal cells in the secretory phase. […] It was observed that the ACE2 mRNA and protein abundance increased during primary human endometrial stromal cell (HESC) decidualization. […] Furthermore, HESCs transfected with ACE2-targeting siRNA impaired the full decidualization response, as evidenced by a lack of morphology change and lower expression of the decidualization markers PRL and IGFBP1. […] Additionally, in mice during pregnancy, the ACE2 protein was expressed in the uterine epithelial cells, and stromal cells increased through day 6 of pregnancy. […] Finally, progesterone induced Ace2 mRNA expression in mouse uteri more than vehicle or estrogen. […] These data establish a role for ACE2 in endometrial physiology, suggesting that SARS-CoV-2 may be able to enter endometrial stromal cells and elicit pathological manifestations in women with COVID-19, including an increased risk of early pregnancy loss.
33205496 This literature review provides an overview of recent studies of genetic polymorphisms in genes that mediate the SARS-CoV-2 infection mechanism (ACE1, ACE2, TMPRSS2 and CD26).
33206176 Angiotensin-converting enzyme 2 (ACE2) is the cellular entry point for severe acute respiratory syndrome coronavirus (SARS-CoV-2)-the cause of coronavirus disease 2019 (COVID-19). […] However, the effect of renin-angiotensin system (RAS)-inhibition on ACE2 expression in human tissues of key relevance to blood pressure regulation and COVID-19 infection has not previously been reported. […] We examined how hypertension, its major metabolic co-phenotypes, and antihypertensive medications relate to ACE2 renal expression using information from up to 436 patients whose kidney transcriptomes were characterized by RNA-sequencing. […] Our data reveal increasing expression of ACE2 with age in both human lungs and the kidney. […] We show no association between renal expression of ACE2 and either hypertension or common types of RAS inhibiting drugs. […] We demonstrate that renal abundance of ACE2 is positively associated with a biochemical index of kidney function and show a strong enrichment for genes responsible for kidney health and disease in ACE2 co-expression analysis. […] Our data further suggest that in the absence of SARS-CoV-2 infection, kidney ACE2 is most likely nephro-protective but the age-related increase in its expression within lungs and kidneys may be relevant to the risk of SARS-CoV-2 infection.
33207244 Given literature suggesting a potential association between SARS-CoV-2 infection and diabetes induction, we examined pancreatic expression of angiotensin-converting enzyme 2 (ACE2), the key entry factor for SARS-CoV-2 infection. […] Specifically, we analyzed five public scRNA-seq pancreas datasets and performed fluorescence in situ hybridization, western blotting, and immunolocalization for ACE2 with extensive reagent validation on normal human pancreatic tissues across the lifespan, as well as those from coronavirus disease 2019 (COVID-19) cases. […] These in silico and ex vivo analyses demonstrated prominent expression of ACE2 in pancreatic ductal epithelium and microvasculature, but we found rare endocrine cell expression at the mRNA level. […] These results suggest SARS-CoV-2 infection of pancreatic endocrine cells, via ACE2, is an unlikely central pathogenic feature of COVID-19-related diabetes.
33207245 This would require binding and entry of SARS-CoV-2 into β cells via co-expression of its canonical cell entry factors, angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2); however, their expression in human pancreas has not been clearly defined. […] We analyzed six transcriptional datasets of primary human islet cells and found that ACE2 and TMPRSS2 were not co-expressed in single β cells. […] In pancreatic sections, ACE2 and TMPRSS2 protein was not detected in β cells from donors with and without diabetes. […] Instead, ACE2 protein was expressed in islet and exocrine tissue microvasculature and in a subset of pancreatic ducts, whereas TMPRSS2 protein was restricted to ductal cells. […] These findings reduce the likelihood that SARS-CoV-2 directly infects β cells in vivo through ACE2 and TMPRSS2.
33207533 We provide a collection of high-probability miRNA binding sites within the SARS-CoV-2 genome as well as within mRNA transcripts of critical viral entry proteins ACE2 and TMPRSS2 and their upstream modulators, the interferons (IFN). […] In particular, we identify predicted miRNA binders to SARS-CoV-2 ORFs (miR-23a (1ab), miR-29a, -29c (1ab, N), miR-151a, -151b (S), miR-4707-3p (S), miR-298 (5’-UTR), miR-7851-3p (5’-UTR), miR-8075 (5’-UTR)), ACE2 3’-UTR (miR-9-5p, miR-218-5p), TMPRSS2 3’-UTR (let-7d-5p, -7e-5p, miR-494-3p, miR-382-3p, miR-181c-5p), and IFN-α 3’-UTR (miR-361-5p, miR-410-3p).
33208074 Structural analysis and evidences have been indicated that interaction between a segment of receptor binding domain (RBD) from S protein of virus and human angiotensin-converting enzyme 2 (hACE2) is essential for cellular entry of virus. […] The current review put the light on structural aspects for inhibition of RBD-hACE2 interaction mediated cellular entry of SARS-CoV-2. […] The present study provides a critical review of recently published information on RBD-hACE2 interaction and its inhibitors to control SARS-CoV-2 infection. […] The review highlighted the structural aspects of interaction between RBDhACE2 and involved amino acid residues. […] One of the important targets for viral invasion is its binding with cell surface receptor, hACE2, through RBD on S-protein. […] Mimicking of three residues on ACE2 (Lys31, Glu35 and Lys353 on B chain) provided hot target directed strategy for inhibition of early attachment of virus to the cell. […] Early screening of peptidic or non-peptidic molecules for inhibition of RBD-hACE2 interaction has been raised the hope for potential therapeutics against COVID-19. […] The higher affinity of molecules toward RBD than ACE2 is important factor for selectivity and minimization of ACE2 related adverse events on cardiovascular system, brain, kidney, and foetus development during pregnancy. […] Inhibition of RBD-hACE2 interaction by different molecular scaffolds can be used as a preferred strategy for control of SARS-CoV-2 infection. […] Recently, published reports pointed out Lys31, Glu35 and Lys353 on B chain of ACE2 as crucial residues for mimicking and design of novel molecules as inhibitors SARS-CoV-2 attachment to human cells. […] Moreover, some recently identified RBD-hACE2 interaction inhibitors have also been described with their protein binding pattern and potencies (IC50 values) which will help for further improvement in the selectivity.
33209137 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted to humans mainly via contact and droplet transmission and its entry into cells is mediated by the efficient binding of the spike (S) viral protein with the angiotensin converting enzyme-2 (ACE2) receptors.
33210300 In the current study, we have compared spike proteins from three strains of coronaviruses NL63, SARS-CoV, and SARS-CoV, known to bind human angiotensin-converting enzyme 2 (ACE2), in terms of sequence/structure conservation, hydrophobic cluster formation and importance of binding site residues. […] The similarities and differences in the spike proteins of the three viruses indicated in this study may help researchers to deeply understand the structural behavior, binding site properties and etiology of ACE2 binding, accelerating the screening of potential lead molecules and the development/repurposing of therapeutic drugs.
33210622 Biological factors include - an absence of X-chromosomes (a powerhouse for immune-related genes), a high level of testosterone that inhibits antibody production, and the presence of Angiotensin-converting enzyme 2 (ACE2) receptors that facilitate viral replication.
33210709 The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is responsible for the global corona virus disease 2019 (COVID-19) pandemic enters host cells via a mechanism that includes binding to angiotensin converting enzyme (ACE) 2 (ACE2). […] Membrane-bound ACE2 is depleted as a result of this entry mechanism. […] The consequence is that the protective renin-angiotensin system (RAS), of which ACE2 is an essential component, is compromised through lack of production of the protective peptides angiotensin-(1-7) and angiotensin-(1-9), and therefore decreased stimulation of Mas (receptor Mas) and angiotensin AT2-receptors (AT2Rs), while angiotensin AT1-receptors (AT1Rs) are overstimulated due to less degradation of angiotensin II (Ang II) by ACE2.
33210729 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry factors, ACE2 and TMPRSS2, are highly expressed in nasal epithelial cells. […] The expression of ACE2 and TMPRSS2 was assessed in nasal tissues of control subjects and eosinophilic CRSwNP (ECRSwNP) and nonECRSwNP patients. […] The correlations between ACE2/TMPRSS2 expression and inflammatory indices of CRSwNP endotypes were evaluated. […] Regulation of ACE2/TMPRSS2 expression by inflammatory cytokines and glucocorticoids was investigated. […] ACE2 expression was significantly increased in nasal tissues of nonECRSwNP patients compared to ECRSwNP patients and control subjects, and positively correlated with the expression of IFN-γ, but negatively correlated with tissue infiltrated eosinophils, and expression of IL5 and IL13. […] IFN-γ up-regulated ACE2 expression while glucocorticoid attenuated this increase in cultured nasal epithelial cells. […] Genes co-expressed with ACE2 were enriched in pathways relating to defence response to virus in nasal tissue. […] Glucocorticoid treatment decreased ACE2 expression in nasal tissues of nonECRSwNP patients, but not in ECRSwNP patients, whereas TMPRSS2 expression was not affected. […] These findings indicate that ACE2 expression, regulated by IFN-γ, is increased in nasal tissues of nonECRSwNP patients and positively correlates with type 1 inflammation.
33210953 (papain-like protease), RdRp (RNA-dependent RNA polymerase), S protein (viral spike glycoprotein), TMPRSS2 (transmembrane protease serine 2), ACE2 (angiotensin-converting enzyme 2), and AT2 (angiotensin AT2 receptor) are important targets.
33211371 Moreover, using pseudotyped virus model, AZ could also markedly block the entry of SARS-CoV-2 in HEK293T-ACE2 and Caco2 cells.
33211435 Inhaled corticosteroids (ICS) were found to reduce expression of ACE2 receptor in sputum cells, thereby maybe reducing the risk of lung infection.
33215463 It further adds the ACE2 receptor role in diabetes with COVID-19 patients.
33215503 In this sense, saliva has proven to be a strategic biofluid, owing not only to its appeal as a noninvasive sampling method but also due to the capacity of the virus to invade epithelial cells of the oral mucosa and salivary gland ducts via ACE2 receptors.
33216184 COVID-19 is a respiratory infectious disease and SARS-CoV-2 replication and shedding occurs in nasal and bronchial epithelial respiratory cells through the interaction with ACE2 and TMPRSS2 receptors, both overexpressed in smokers and former smokers.
33216381 SARS-CoV-2 uses angiotensin converting enzyme 2 (ACE2) receptor to enter the host cell and primarily target type II alveolar cells.
33217033 Angiotensin-converting enzyme-2 (ACE2) is the receptor for SARS-CoV-2. […] Animal studies suggest that renin-angiotensin-aldosterone system (RAAS) blockers might increase the expression of ACE2 and potentially increase the risk of SARS-CoV-2 infection.
33218024 value of 1.5 nM against the ACE2. […] Collectively, we suggest that drugs predicted to have strong inhibitory potencies to ACE2 and TMPRSS2 through the DTI model should be considered as potential drug repurposing candidates for COVID-19.
33220921 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped virus which binds its cellular receptor angiotensin-converting enzyme 2 (ACE2) and enters hosts cells through the action of its spike (S) glycoprotein displayed on the surface of the virion. […] Residue 614 lies outside the receptor binding domain (RBD) and the mutation does not alter the affinity of monomeric S protein for ACE2. […] However, S(G614), compared to S(D614), mediates more efficient ACE2-mediated transduction of cells by S-pseudotyped vectors and more efficient infection of cells and animals by live SARS-CoV-2.
33221119 Molecular docking analysis to evaluate the effect of the mutations on the interaction between the viral spike proteins and the human ACE2 receptor, though no significant difference was observed.
33221318 The virus mainly spreads through the respiratory tract, uses angiotensin-converting enzyme 2 (ACE2) as a receptor, and is characterized by symptoms of fever, cough, and fatigue.
33223324 Interaction of the spike glycoprotein with ACE2 receptor present in the host cell surface mediates the entry of SARS-CoV-2 causing COVID-19 infection. […] To address this issue, we hypothesis that, high ACE2 expression in the endothelium of blood vessels facilitates the high-affinity binding of SARS-CoV-2 using spike protein, causing infection and internal injury inside the vascular wall of blood vessels.
33224265 The virus-host interaction of SARS-CoV-2 uses the same receptor, ACE2, which is similar to that of SARS-CoV, which spreads through the respiratory tract.
33224380 Enhanced ACE2 expression, pre-existing endothelial dysfunction and procoagulant state induced by adipocytokines dysregulation in metabolic syndrome may play a crucial role for the development of severe COVID-19.
33224734 In this study, it was aimed to reveal potential miRNA targets for the regulation of SARS-CoV-2 host cell receptor ACE2. […] For the identification of potential miRNA targets for the ACE2 gene, TarBase v.8 (DIANA Tools), TargetScan, miRTarBase and miRDB miRNA-target prediction algorithms were used. […] The results suggest that members of miR-200 family of miRNAs, especially miR-200c-3p, are strong candidate targets for the regulation of ACE2 in respiratory system cells.
33226581 Furthermore, an in silico data have been provided in support of the “probiotics-derived lipopeptides” role in inactivating spike (S) glycoprotein of SARS-CoV-2 and its host receptor molecule, ACE2. […] Among well characterized lipopeptides derived from different probiotic strains, subtilisin (Bacillus amyloliquefaciens), curvacin A (Lactobacillus curvatus), sakacin P (Lactobacillus sakei), lactococcin Gb (Lactococcus lactis) was utilized in this study to demonstrate a higher binding proclivity to S-protein of SARS-CoV-2 and human ACE2. […] The outcome revealed noteworthy capabilities of the lipopeptides, due to their amphiphilic nature, to bind spike protein and receptor molecule, which may act to competitively inhibit the mandatory interaction of SARS-CoV-2 with the host epithelial cell expressing ACE2 for its entry into the cell for reproduction.
33226815 According to the crystal structure of angiotensin-converting enzyme 2 (ACE2), which binds to the SARS-CoV-2 receptor binding domain (RBD), 15 amino acids of ACE2 have considerable interaction with RBD. […] Among the studied nanoparticles, the AuNP functionalized by new peptide forms a more stable complex with RBD in comparison with ACE2, which is the human receptor for SARS-CoV-2.
33226885 The SARS-CoV-2 peripheral Spike-Fc protein binds specifically to the ACE2 receptors present on bronchial epithelial cells and alveolar pneumocytes to downmodulates its expression which leads to severe acute respiratory failure.
33227636 A critical review and robust Bayesian analysis of the hypothesis is described here, finding no conclusive evidence of COVID-19 mortality and 2D:4D, nor associations between 2D:4D and ACE1 allele or ACE2 genotype frequency.
33227700 Severe acute respiratory syndrome (SARS) develops within 3-14 days when CoV2 invades epithelial, myeloid cells in the nasopharynx and pneumocytes in the respiratory tract through angiotensin converting enzyme (ACE2).
33228225 The virus enters the cell through the angiotensin-converting enzyme-2 (ACE2) receptor and plays a central function in the virus’s pathogenesis.
33230174 In this study, we report a unique antiviral platform, through computational design of ACE2-derived peptides which both target the viral spike protein receptor binding domain (RBD) and recruit E3 ubiquitin ligases for subsequent intracellular degradation of SARS-CoV-2 in the proteasome.
33231324 The surface spike protein of SARS-CoV-2 mediates the process of coronavirus entry into human cells by binding angiotensin-converting enzyme 2 (ACE2).
33231569 Angiotensin converting enzyme 2 (ACE2) and Cathepsin L/Cathepsin B (CTSL/B), which act as the receptor and entry-associated proteases of SARS-CoV-2 respectively, are pivotal for SARS-CoV-2 infection. […] To investigate the possible SARS-CoV-2 infection risk of pan-cancer, we analyzed the genetic alterations, RNA expression, DNA methylation, and the association with immune subtypes of ACE2 and CTSL/B with the prognosis in pan-cancer. […] Results showed the upregulation of CTSL/B and ACE2 in Pancreatic adenocarcinoma (PAAD) and Stomach adenocarcinoma (STAD) and demonstrated a positive correlation between copy number alteration (CNA) and gene expression for CTSB in PAAD and STAD. […] In addition, ACE2 and CTSL/B are overexpressed in the IFN-gamma immune subtype of ovarian serous Cystadenocarcinoma (OV), Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), and Bladder urothelial carcinoma (BLCA).
33231620 Angiotensin converting enzyme-2 (ACE2) is a multifunctional transmembrane protein recently recognised as the entry receptor of the virus causing COVID-19. […] In the renin-angiotensin system (RAS), ACE2 cleaves angiotensin II (Ang II) into angiotensin 1-7 (Ang 1-7), which is considered to exert cellular responses to counteract the activation of the RAS primarily through a receptor, Mas, in multiple organs including skeletal muscle. […] In contrast, there is relatively little evidence to support the protective role of ACE2 in skeletal muscle. […] The potential contribution of endogenous ACE2 to the regulation of Ang 1-7-mediated protection of these muscle pathologies is discussed in this review. […] Recent studies have suggested that ACE2 protects against ageing-associated muscle wasting (sarcopenia) through its function to modulate molecules outside of the RAS. […] Thus, the potential association of sarcopenia with ACE2 and the associated molecules outside of RAS is also presented herein. […] Further, we introduce the transcriptional regulation of muscle ACE2 by drugs or exercise, and briefly discuss the potential role of ACE2 in the development of COVID-19.
33232663 The infection occurs through binding of the virus with angiotensin converting enzyme 2 (ACE2) on the cell membrane. […] Here, we established a screening strategy to identify drugs that reduce ACE2 levels in human embryonic stem cell (hESC)-derived cardiac cells and lung organoids. […] Target analysis of hit compounds revealed androgen signaling as a key modulator of ACE2 levels. […] Treatment with antiandrogenic drugs reduced ACE2 expression and protected hESC-derived lung organoids against SARS-CoV-2 infection.
33232769 Currently, the world is suffering from the pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that uses angiotensin-converting enzyme 2 (ACE2) as a receptor to enter the host cells. […] The recombinant protein that contains only the ACE2 receptor-binding domain of the SARS-CoV-2 spike protein S1 subunit (Arg319 - Phe541), on the other hand, did not cause this activation.
33232865 This suggests that besides human ACE2, an additional or alternate receptor for SARS-CoV-2 is likely to exist.