angiotensin I converting enzyme

Gene Context Sentence

Table 2. Analysis of context sentence of ACE gene in 527 abstracts.

PMID Gene Context Sentence
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. […] Increased ACE and Ang II are poor prognostic factors for severe pneumonia. […] The binding of COVID-19 and ACE2 resulted in the exhaustion of ACE2, and then ACE2/Ang (1-7)/Mas receptor pathway was inhibited. […] The balance of the RAS system was broken, and this would lead to the exacerbation of acute severe pneumonia. […] Therefore, we speculate that ACEI and AT1R inhibitors could be used in patients with COVID-19 pneumonia under the condition of controlling blood pressure, and might reduce the pulmonary inflammatory response and mortality. […] 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。 […] ACE和Ang II升高是重症肺炎的不良预后因素。 […] 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。 […] 因此,在控制血压的情况下,对新型冠状病毒肺炎患者应用ACEI及AT1R抑制剂,有可能减轻患者肺部炎症反应,降低患者病死率。.
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. […] Increased ACE and Ang II are poor prognostic factors for severe pneumonia. […] The binding of COVID-19 and ACE2 resulted in the exhaustion of ACE2, and then ACE2/Ang (1-7)/Mas receptor pathway was inhibited. […] The balance of the RAS system was broken, and this would lead to the exacerbation of acute severe pneumonia. […] Therefore, we speculate that ACEI and AT1R inhibitors could be used in patients with COVID-19 pneumonia under the condition of controlling blood pressure, and might reduce the pulmonary inflammatory response and mortality.
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.
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.
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.
32229706 One is CD26 and the other is ACE-2 (angiotensin-converting enzyme 2).
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.
32242182 There has been a lot of speculation that patients with coronavirus disease 2019 (COVID-19) who are receiving angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) may be at increased risk for adverse outcomes.
32247213 Search terms were, COVID-19, treatment of coronavirus, COVID 19 and following terms; chloroquine, hydroxychloroquine, ibuprofen, ACE-inhibitors or angiotensin receptor blockers, cardiovascular disease, diarrhoea, liver, testis and gastrointestinal disease.
32250244 The discovery that SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) binds to the angiotensin converting enzyme (ACE)-2, which is highly expressed in the lower airways, explained why SARS-CoV-2 causes acute respiratory distress syndrome (ARDS) and respiratory failure. […] After this, news spread that ACEis and ARBs would be harmful in SARS-CoV-2-infected subjects. […] To the contrary, compelling evidence exists that the ACE-1/angiotensin(Ang)II/ATR-1 pathway is involved in SARS-CoV-2-induced ARDS, while the ACE-2/Ang(1-7)/ATR2/MasR pathway counteracts the harmful actions of AngII in the lung. […] A reduced ACE-1/ACE-2 ratio is, in fact, a feature of ARDS that can be rescued by human recombinant ACE-2 and Ang(1-7) administration, thus preventing SARS-CoV-2-induced damage to the lung. […] Based on the current clinical evidence treatment with ACE-inhibitors I (ACEis) or angiotensin receptor blockers (ARBs) continues to provide cardiovascular and renal protection in patients diagnosed with COVID-19.
32251731 The first step of the viral replication cycle [i.e. attachment to the surface of respiratory cells, mediated by the spike (S) viral protein] offers several potential therapeutic targets. […] The S protein uses the angiotension-converting enzyme-2 (ACE-2) receptor for entry, but also sialic acids linked to host cell surface gangliosides. […] This domain (111-158), which is fully conserved among clinical isolates worldwide, may improve attachment of the virus to lipid rafts and facilitate contact with the ACE-2 receptor.
32255507 Additionally, many adults with hypertension, diabetes, and chronic kidney disease are placed on angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs). […] Studies have shown that these medications upregulate the ACE-2 receptor, the very receptor which the SARS-CoV-2 virus uses to enter host cells, which puts older adults at a further increased risk of infection.
32266708 Cardiovascular diseases, in particular hypertension, as well as the cardiovascular treatment with Renin-Angiotensin System inhibitors such as Angiotensin Converting Enzyme (ACE) inhibitors and Angiotensin Receptor Blockers (ARBs), are claimed once again as mechanisms of Severe Acute Respiratory Syndrome (SARS) during the COVID-19 outbreak due to Cov-2 epidemics. […] In vitro studies are available to support the eventual role of ACE inhibitors and ARBs in both the promotion and antagonism of the disease.
32268343 The possible reason about non-susceptibility of children to coronavirus may lie in different angiotensin-converting enzyme (ACE) activity and immunity of children.The first possible reason is about ACE activity. […] A research revealed that children had higher ACE activities.
32269893 Emphasis is placed on evidence-based medicine to evaluate the frequency of presentation of various symptoms to create a stratification system of the most important epidemiological risk factors for COVID-19. […] Lastly, the current scientific data and status of governing bodies such as the Center of Disease Control (CDC) and the WHO on the usage of controversial therapies such as angiotensin-converting enzyme (ACE) inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs) (Ibuprofen), and corticosteroids usage in COVID-19 are discussed.
32274964 Angiotensin-converting enzyme-2 (ACE-2) is one of the most important receptors on the cell membrane of the host cells (HCs) which its interaction with spike protein (SP) with a furin-cleavage site results in the SARS-CoV-2 invasion. […] Hence, in this review, we presented an overview on the interaction of ACE-2 and furin with SP. […] Furthermore, we discussed that the small molecular inhibitors can limit the interaction of ACE-2 and furin with SP and can be used as potential therapeutic platforms to combat the spreading CoV epidemic.
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.
32279064 Similar to the respiratory mucosa, angiotensin converting enzyme-2 (ACE-2) receptor and transmembrane serine protease 2 TMPRSS2) co-express in the gastrointestinal tract, which facilitates viral entry into the tissue.
32297723 Structural analysis of the receptor binding site has confirmed that 2019-nCoV binds with the same ACE 2 receptor protein as human SARS virus.
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.
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.
32310915 Some Authors recently suggested that angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) should be discontinued, even temporarily, given the current pandemic of SARS-CoV-2 virus. […] The suggestion is based on the hypothesis that ACE-inhibitors and ARBs may favor the entry and diffusion of SARS-CoV-2 virus into the human cells. […] 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. […] In the light of the above considerations, it is reasonable to conclude that the suggestion to discontinue ACE-inhibitors or ARBs in all patients with the aim of preventing or limiting the diffusion of SARS-CoV-2 virus is not based on clinical evidence. […] This review discusses facts and theories on the potential impact of ACE-inhibitors and ARBs in the setting of the SARS-CoV-2 pandemic.
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.
32320687 Taxonomically, SARS-CoV-2 was shown to be a Betacoronavirus (lineage B) closely related to SARS-CoV and SARS-related bat coronaviruses, and it has been reported to share a common receptor with SARS-CoV (ACE-2). […] Compared to SARS-CoV and all other coronaviruses in Betacoronavirus lineage B, we identify an extended structural loop containing basic amino acids at the interface of the receptor binding (S1) and fusion (S2) domains.
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. […] Based on our analysis and evaluation of the available findings, we justify our conclusion: important drugs such as ACE inhibitors and angiotensin receptor blockers should continue to be prescribed according to guidelines to stable patients in the context of the COVID-19 pandemic.
32324352 There is no preference for either ACE inhibitors or angiotensin II receptor inhibitors.
32328850 More importantly, angiotensin-converting enzyme (ACE)-2, the SARS-CoV-2 receptor, has been proven highly increased during pregnancy, which may contribute to the susceptibility to SARS-CoV-2.
32330817 Of the 33 studied patients, 91% were male, median age 64; 88% were overweight or obese. 45% were hypertensive, 12% had been taking an ACE-inhibitor.
32335337 The angiotensin-converting enzyme (ACE) system is not uniformly expressed in all of the human races, and current differences could explain some of the geographical discrepancies in infection around the world. […] 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. […] As two-thirds of hypertensive patients take ACE inhibitors/angiotensin receptor blockers, several concerns have been raised about the detrimental role of current antihypertensive drugs in COVID-19. […] This report summarizes the recent evidence for and against the administration of ACE blockade in the COVID-19 era.
32336586 This narrative review was conducted to summarize the effectiveness of current therapy options for COVID-19 and address the controversial use of non-steroidal anti-inflammatory drugs (NSAIDs), angiotensin converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs). […] ACE inhibitors and ARBs should not be discontinued at this time and ibuprofen may be used for fever.
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. […] Increased pulmonary inflammation and coagulation have been reported as unwanted effects of enhanced and unopposed angiotensin II effects via the ACE→Angiotensin II→AT1 receptor axis. […] 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.
32338224 SARS-CoV binds to the angiotensin-converting enzyme (ACE)2 which is present on nonimmune cells, such as respiratory and intestinal epithelial cells, endothelial cells, kidney cells (renal tubules) and cerebral neurons and immune cells, such as alveolar monocytes/macrophages [4-6]. […] 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]. […] However, the putative effects of ACE-2 down-regulation on the cardiovascular system in the course of COVID-19 pandemic need more intensive studies. […] 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.
32340044 The SARS-CoV-2 infects humans through the angiotensin converting enzyme (ACE-2) receptor. […] The ACE-2 receptor is a part of the dual system renin-angiotensin-system (RAS) consisting of ACE-Ang-II-AT1R axis and ACE-2-Ang-(1-7)-Mas axis. […] In metabolic disorders and with increased age, it is known that there is an upregulation of ACE-Ang-II-AT1R axis with a downregulation of ACE-2-Ang-(1-7)-Mas axis. […] The activated ACE-Ang-II-AT1R axis leads to pro-inflammatory and pro-fibrotic effects in respiratory system, vascular dysfunction, myocardial fibrosis, nephropathy, and insulin secretory defects with increased insulin resistance. […] On the other hand, the ACE-2-Ang-(1-7)-Mas axis has anti-inflammatory and antifibrotic effects on the respiratory system and anti-inflammatory, antioxidative stress, and protective effects on vascular function, protects against myocardial fibrosis, nephropathy, pancreatitis, and insulin resistance. […] The already strained ACE-2-Ang-(1-7)-Mas in metabolic disorders is further stressed due to the use of the ACE-2 by the virus for entry, which affects the prognosis in terms of respiratory compromise. […] Further evidence needs to be gathered on whether modulation of the renin angiotensin system would be advantageous due to upregulation of Mas activation or harmful due to the concomitant ACE-2 receptor upregulation in the acute management of COVID-19.
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. […] Importantly, however, there is no clinical or experimental evidence supporting that ARBs and ACEIs either augment the susceptibility to SARS-CoV-2 or aggravate the severity and outcomes of COVID-19 at present. […] Until further data are available, it is recommended that ARB and ACEI medications be continued for the treatment of patients with cardiovascular disease and hypertension, especially those at high risk, according to guideline-directed medical therapy based on the currently available evidence.
32343593 Although SARS-CoV-2 may primarily enter the cells of the lungs, the small bowel may also be an important entry or interaction site, as the enterocytes are rich in angiotensin converting enzyme (ACE)-2 receptors. […] The separation of the S-spike into S1 and S2 is essential for the attachment of the virion to both the ACE receptor and the cell membrane.
32344526 The scientific community has recently focused its attention on angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor 1 (AT1R) inhibitors and their possible benefit/harms for patients infected by Coronavirus disease (COVID-19) who experience pneumonia, but there are still some doubts about the effects of these drugs in this setting.
32348052 ACE inhibitors and sartans upregulate the expression of angiotensin-converting enzyme 2 (ACE2), the pulmonary receptor for SARS-CoV-2. […] Les AINS pourraient interférer avec le processus de défense face à une infection virale ; ils sont donc plutôt à éviter. […] Les IEC et les sartans modulent l’expression de l’enzyme de conversion de l’angiotensine 2 (ACE2), récepteur pulmonaire du SARS-CoV-2.
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. […] In this article, we are focusing on the impact of ACE inhibitors (ACEI) and DPP4 inhibitors used on SARS-CoV-2 activity and discussions about those drugs that may be related to infectious condition of COVID-19 diseases.
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.
32352944 S-proteins covering its surface, which bind to the cell receptor - angiotensin converting enzyme 2 (ACE-2) and transmembrane serine protease (TMPRSS2) are important in shaping virus activity.
32356252 ACE inhibitors and ibuprofen have been suggested to exacerbate the pathogenesis of COVID-19.
32356626 Concern has been aroused regarding a potential harmful effect of angiotensin-converting-enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) in this clinical context. […] No increased risk of in-hospital death was found to be associated with the use of ACE inhibitors (2.1% vs. […] Our results did not confirm previous concerns regarding a potential harmful association of ACE inhibitors or ARBs with in-hospital death in this clinical context.
32356627 A potential association between the use of angiotensin-receptor blockers (ARBs) and angiotensin-converting-enzyme (ACE) inhibitors and the risk of coronavirus disease 2019 (Covid-19) has not been well studied. […] The use of ACE inhibitors and ARBs was more common among case patients than among controls, as was the use of other antihypertensive and non-antihypertensive drugs, and case patients had a worse clinical profile. […] Use of ARBs or ACE inhibitors did not show any association with Covid-19 among case patients overall (adjusted odds ratio, 0.95 [95% confidence interval {CI}, 0.86 to 1.05] for ARBs and 0.96 [95% CI, 0.87 to 1.07] for ACE inhibitors) or among patients who had a severe or fatal course of the disease (adjusted odds ratio, 0.83 [95% CI, 0.63 to 1.10] for ARBs and 0.91 [95% CI, 0.69 to 1.21] for ACE inhibitors), and no association between these variables was found according to sex. […] In this large, population-based study, the use of ACE inhibitors and ARBs was more frequent among patients with Covid-19 than among controls because of their higher prevalence of cardiovascular disease. […] However, there was no evidence that ACE inhibitors or ARBs affected the risk of COVID-19.
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). […] We assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive.
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). […] Then, using a logical evaluation of viral density that measures the rate at which the cells are hijacked by the virus (and they provide a place for the virus to replicate) and considering the “time delay” given by the interaction between cell and virus, the expected duration of the incubation period is predicted. […] The amino acid sequence of S proein and its interaction with the ACE-2 protein is mimicked with the aid of Hill function.
32364011 Although, captopril is shown to be a potential ligand of 3CLpro, it is not recommended anti-COVID-19 therapy, due to the fact that it can induce the expression of the viral cellular receptor such as, angiotensin-converting enzyme ACE-2, and thus, making the patient potentially more susceptible to infection.
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. […] We further explore the impact of underlying medical conditions and therapies including renin-angiotensin inhibitors on modulating ACE 2, which is the major SARS-CoV-2 cell entry receptor.
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.
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 .
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.
32375574 This study demonstrated the putative inhibitory potential of lopinavir, remdesivir, oseltamir, azithromycin, ribavirin, and chloroquine towards V-ATPase, protein kinase A, SARS-CoV spike glycoprotein/ACE-2 complex and viral proteases. […] Lopinavir has the highest binding affinities to the pocket site of SARS-CoV spike glycoprotein/ACE-2 complex, cyclic AMP-dependent protein kinase A and 3-Chymotrypsin like protease while redemsivir has the highest binding affinities for vacuolar proton-translocating ATPase (V-ATPase) and papain-like proteins. […] The amino acids Asp269, Leu370, His374, and His345 were predicted as the key residues for lopinavir binding to human SARS-CoV spike glycoprotein/ACE-2 complex while His378, Tyr515, Leu73, Leu100, Phe32 and Phe40 for remdesivir and Tyr510, Phe504, Met62, Tyr50, and His378 were predicted for azithromycin as the key residues for binding to SARS-CoV spike glycoprotein/ACE-2 complex.
32380453 Since the ACE-2 was expressing on oral cavity mucosa, there is a potentially huge COVID-19 infectious vulnerability risk for oral cavity and brought up a proof for the future prevention procedure in dental practice and daily life.
32387238 SARS-CoV-2 has a major impact on the Renin Angiotensin Aldosterone System (RAAS), through its binding to the membrane cellular glycoprotein, Angiotensin Converting Enzyme-2 (ACE-2), then infecting cells for replication. […] This report hypothesizes the possible implication of an autoimmune response, induced by generation of allo- or autoantibodies to ACE-2, or to its complexes with viral spike protein.
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.
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. […] Furthermore, considering the common role of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway in AT1-R expressed on peripheral tissues and cytokine receptors on the surface of immune cells, potential targeting of this pathway using JAK inhibitors (JAKinibs) is suggested as a promising approach in patients with COVID-19 who are admitted to hospitals. […] 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.
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). […] Currently doctors concern whether these commonly used renin-angiotensin system (RAS) blockers-ACEIs/ARBs may increase the severity of COVID-19. […] These data suggest ACEIs/ARBs may have few effects on increasing the clinical severe conditions of COVID-19.
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.
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.
32405156 CLQ-OH molecules are shown to saturate virus attachment sites on gangliosides in the vicinity of the primary coronavirus receptor, angiotensin-converting enzyme-2 (ACE-2).
32405183 These are postulated to be related to the virus’s use of ACE-2 receptors located on certain intestinal cells, cholangiocytes, and hepatocytes.
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.
32409498 Clinical outcomes of those who use an ACE inhibitor (ACEI) or angiotensin II type-I receptor blocker (ARB) were comparable with those of patients who do not use ACEI/ARB among patients with diabetes and hypertension who have COVID-19. […] ACEI/ARB use showed no significant impact on patients with diabetes and hypertension who have 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.
32410003 The expression of primary target receptor for SARS-CoV-2, i.e. angiotensin converting enzyme-2 (ACE-2), decreases with age. […] ACE-2 has lung protective effects by limiting angiotensin-2 mediated pulmonary capillary leak and inflammation.
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. […] Recent data show the lack of untoward effects of ACE inhibitors or angiotensin receptor blockers for COVID-19 infection and severity.
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. […] We propose that medications which inhibit the RAS ACE-dependent pathway may be beneficial in treating COVID-19 and should be explored in animal models and clinical trials.
32417709 This is a narrative mini-review with Pubmed search until April 23, 2020 using the keywords COVID-19, SARS-CoV-2, treatment of coronavirus and following terms: diabetes mellitus, obesity, arterial hypertension, ACE-inhibitors, cytokine storm, immune response and vitamin D. […] 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. […] The cellular targets of Angiotensin II are the vasoconstrictor type 1 (AT1R) and vasodilatator type 2 (AT2R) Angiotensin II receptors (AT1R is expressed at the surface of monocytes/macrophages and T-cells indicating that RAS acts on innate immunity in host). […] 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. […] The proposed molecules are (so far) ACE inhibitors (to prevent the production of Angiotensin II from Angiotensin I), and blockers/antagonists of AT1R such as Losartan and derivatives. […] 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.
  1. Background: Combating viral disease outbreaks has doubtlessly been one of the major public health challenges for the 21st century. (2) Methods: The host entry machinery required for COVID-19 (SARS-CoV-2) infection was examined for the gene expression profiles and polymorphism. (3) Results: Lung, kidney, small intestine, and salivary glands were among the tissues which expressed the entry machinery coding genes Ace2, Tmprss2, CtsB, and CtsL. […] 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. […] Different levels of expression and function of ACE proteins, underlying disorders, consumption of certain medications and the existence of certain genomic variants within ACE genes are possible explanations for the observed difference in the response of individuals to the SARS-CoV-2 infection.
32428113 Toward this, we raise two main </mac_aq>points, i) increased ACE-2 expression in pulmonary and heart tissues in users of chronic angiotensin 1 </mac_aq>receptor (AT1R) blockers; and ii) antibody-dependent enhancement (ADE) after previous exposure to other circulating coronaviruses.
32430651 SARS-CoV-2 is characterized by a spike protein allowing viral binding to the angiotensin-converting enzyme (ACE)-2, which acts as a viral receptor and is expressed on the surface of several pulmonary and extra-pulmonary cell types, including cardiac, renal, intestinal and endothelial cells. […] In clinical practice, angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin II receptor blockers (ARBs) are extensively used for the treatment of hypertension and other cardiovascular diseases. […] In in vivo studies, ACE-Is and ARBs seem to paradoxically increase ACE-2 expression, which could favour SARS-CoV-2 infection of host’s cells and tissues. […] By contrast, in patients treated with ACE-Is and ARBs, ACE-2 shows a downregulation at the mRNA and protein levels in kidney and cardiac tissues. […] Yet, it has been claimed that both ARBs and ACE-Is could result potentially useful in the clinical course of SARS-CoV-2-infected patients. […] Older COVID-19-affected patients with cardiovascular comorbidities exhibit a more severe clinical course and a worse prognosis, with many of them being also treated with ARBs or ACE-Is. […] Another confounding factor is cigarette smoking, which has been reported to increase ACE-2 expression in both experimental models and humans. […] Sex also plays a role, with chromosome X harbouring the gene coding for ACE-2, which is one of the possible explanations of why mortality in female patients is lower. […] Despite the relevance of experimental animal studies, to comprehensively address the question of the potential hazards or benefits of ACE-Is and ARBs on the clinical course of COVID-19-affected patients treated by these anti-hypertensive drugs, we will need randomized human studies. […] We claim the need of adequately powered, prospective studies aimed at answering the following questions of paramount importance for cardiovascular, internal and emergency medicine: Do ACE-Is and ARBs exert similar or different effects on infection or disease course? […] Since ACE-Is and ARBs have different molecular targets, the clinical course of SARS-CoV-2 infection could be also different in patients treated by one or the other of these two drug classes.
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.
32442082 SARS-CoV-2 penetrates via human angiotensin-converting enzyme-2 receptor (ACE-2) that was also utilized by severe acute respiratory syndrome coronavirus (SARS CoV) [3]. […] Glial cells and neurons have been reported to express ACE-2 receptors, which make them a potential target of COVID-19. […] Thus, dementia researchers and pharmaceutical companies should determine an emergency action plan to exit the chaos of this pandemic. […] The closing of universities may lead to data loss, death of expensive transgenic animals, international researchers to be faced with visa problems, and be lost the laboratory staff whose contract has expired [7]. […] It is also known that movement restriction exacerbates AD symptoms [10]. […] Therefore, a collective action plan protecting dementia research during the COVID-19 outbreak should be prepared by a consortium of pharmaceutical companies, researchers, clinicians, and patients. […] For example, research funders and pharmaceutical companies can extend project deadlines and provide an additional promotion to the researchers who have completed their clinic trails.
32447007 Chronic exposure to air pollutants have been associated with lung ACE-2 over-expression which is known to be the main receptor for SARS-coV2. […] From the data available we propose a “double-hit hypothesis”: chronic exposure to PM 2.5 causes alveolar ACE-2 receptor overexpression. […] This may increase viral load in patients exposed to pollutants in turn depleting ACE-2 receptors and impairing host defences. […] High atmospheric NO2 may provide a second hit causing a severe form of SARS-CoV-19 in ACE-2 depleted lungs resulting in a worse outcome.
32447629 Concern about the appropriate role of nonsteroidal anti-inflammatory drugs (NSAIDs) in COVID-19 speculate that NSAIDs, in particular ibuprofen, may upregulate the entry point for the virus, the angiotensin-converting enzyme (ACE) 2 receptors and increase susceptibility to the virus or worsen symptoms in existing disease. […] The Expert Working Group on the Commission of Human Medicines in the UK and other organizations have stated that there is insufficient evidence to establish a link between ibuprofen and susceptibility to or exacerbation of COVID-19. […] Paracetamol (acetaminophen) has been proposed as an alternative to NSAIDs but there are issues with liver toxicity at high doses.
32447630 The spike proteins of both viruses dictate tissue tropism using the angiotensin-converting enzyme type 2 (ACE-2) receptor to bind to cells. […] The ACE-2 receptor can be found in nervous system tissue and endothelial cells among the tissues of many other organs.Neurological complications have been observed with COVID-19.
32448098 The binding of SARS-CoV (CoV) spike protein (S-Protein) Receptor Binding Domain (RBD) to Angiotensin converting enzyme 2 (ACE 2) receptor initiates the entry of corona virus into the host cells leading to the infection. […] 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. […] Based on the hydrogen bonding, RMSD and RMSF, total and potential energies, the nCoV was found binding to ACE 2 receptor with higher stability and rigidity.
32449034 Furthermore, the expression of ACE-2 receptors in absorptive enterocytes from ileum and colon suggests that these organs should also be considered as a potential high risk for SARS-CoV-2 infection.
32450906 We discuss potential sex-specific mechanisms modulating the course of disease, such as hormone-regulated expression of genes encoding for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) entry receptors angiotensin converting enzyme (ACE) 2 receptor and TMPRSS2 as well as sex hormone-driven innate and adaptive immune responses and immunoaging.
32468052 SARS‑CoV‑2 infection of host cells is facilitated by the angiotensin‑converting enzyme 2 (ACE‑2), and by transmembrane protease serine 2 (TMPRSS2) and other host cell proteases such as cathepsin L (CTSL). […] With the exception of ACE‑2, a systematic analysis of these two other SARS‑CoV2 infection mediators in malignancies is lacking.
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.
32469265 SARS-CoV-2 is an enveloped virus and there are ample evidences that its Spike protein (S-protein) is mainly associated with pathogenesis as it is surface-exposed and mediates entry into host cells by binding to angiotensin-converting enzyme-2 (ACE-2) receptor.
32470515 The coronavirus disease 2019 (COVID-19) is caused by SARS-CoV2 that interfaces with the renin-angiotensin-aldosterone system (RAAS) through angiotensin-converting enzyme 2 (ACE-2). […] RASTAVI (NCT03201185) is an ongoing randomized clinical trial randomly allocating Ramipril or control after successful transcatheter aortic valve replacement at 14 centers is Spain.
32470547 Viral dependence on ACE-2, as entry receptors, drove the researchers into RAS impact on COVID-19 pathogenesis.
32472989 A great interest is currently directed towards the angiotensin 2 converting enzyme (ACE 2) which is the SARS-CoV-2 receptor and creates important connections between the virus replication pathway, the cardiovascular system and blood pressure. […] All cardiovascular conditions share an imbalance of the renin angiotensin system (RAAS) in which ACE 2 plays a central role. […] In the last few days, much confusion has appeared about the management of therapy with angiotensin converting enzyme inhibitors (ACE-i) and angiotensin receptor blockers (ARBs) in infected patients and in those at risk of critical illness in case of infection.
32472991 Furthermore, we highlight the relationship between the virus, enzyme ACE2 and ACE inhibitors.
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. […] In addition, the binding energies at the interface are slightly higher for SARS-CoV-2 because of enhanced electrostatic interactions. […] 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.
32485894 It has 79.5% sequence identity with SARS-CoV-1 and the same strategy for host cell invasion through the ACE-2 surface protein.
32489695 The importance of cross-immunity, innate immune responses, ACE polymorphism, and viral genetic mutations are discussed.
32491073 COVID-19 acts through the angiotensin-converting enzyme 2 (ACE2) receptor. […] Further research is needed to continue or discontinue ACE inhibitors and angiotensin receptor blockers, which are essential in hypertension and heart failure in COVID-19.
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.
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 When the coronavirus disease 2019 (COVID-19) wreaked an unprecedented havoc of an escalating number of deaths and hospitalization in the United States, clinicians were faced with a myriad of unanswered questions, one of the them being the implication of the renin-angiotensin-aldosterone system in patients with COVID-19. […] 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. […] This article is to examine and summarize the 2 opposing viewpoints and provide guideline recommendations to support the use or discontinuation of ACE inhibitors and ARBs in patients with COVID-19.
32498135 ACE-I/ARB use and NSAIDs use were widely prevalent (43.3% and 35.7%, respectively). […] NSAIDs and ACE-I/ARB use had no significant effects on renal failure in the first 48 h. […] NSAIDs and ACE-I/ARB use prior to admission is not associated with renal failure or increased mortality.
32504757 The Angiotensin-Converting Enzyme (ACE) 2, is an essential receptor for cell fusion and engulfs the SARS coronavirus infections. […] 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.
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.
32514935 Angiotensin-converting enzyme (ACE) inhibitors (ACEIs) and angiotensin II type‑1 receptor blockers (ARBs) are among the most widely prescribed drugs for the treatment of arterial hypertension, heart failure and chronic kidney disease. […] 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. […] This has led to the hypothesis that use of ACEIs and ARBs may increase the risk of developing severe COVID-19. […] In this point of view paper, possible scenarios regarding the impact of ACEI/ARB pharmacotherapy on COVID-19 are discussed in relation to the currently available evidence. […] Although further research on the influence of blood-pressure-lowering drugs, including those not targeting the renin-angiotensin system, is warranted, there are presently no compelling clinical data showing that ACEIs and ARBs increase the likelihood of contracting COVID-19 or worsen the outcome of SARS-CoV‑2 infections. […] Thus, unless contraindicated, use of ACEIs/ARBs in COVID-19 patients should be continued in line with the recent recommendations of medical societies.
32515379 An expression of the angiotensin-converting enzyme 2 (ACE 2), the cellular receptor for SARS-CoV-2 over the glial cells and neurons have made the brain a potential target.
32516124 It is worthy of note that due to the active anastomosis bleed the angiotensin-converting enzyme (ACE)-inhibitor treatment was stopped, and later the patient got infected with SARS-CoV-2.
32519164 Recent research has revealed that virus entry takes place upon the union of the virus S surface protein with the type I transmembrane metallo-carboxypeptidase, angiotensin converting enzyme 2 (ACE-2) identified on epithelial cells of the host respiratory tract. […] Virus triggers the synthesis and release of pro-inflammatory cytokines, including IL-6 and TNF-α and also promotes downregulation of ACE-2, which promotes a concomitant increase in levels of angiotensin II (AT-II).
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. […] In the meantime, however, the use of RAS blockers such as ACE inhibitors and angiotensin II receptor blockers that inhibit the damaging (ACE-Ang II) arm of the RAS cascade in the lung may also be promising.
32523145 This fact, together with the knowledge that the route of entry of the virus into the cell is precisely the ACE-2 receptor, initiated a hypothesis, based on very low-quality evidence, which quickly became generalized in the media, that the use of these drugs could be negative and that they should be interrupted immediately. […] Casi simultáneamente también apareció la hipótesis, también basada en evidencia muy preliminar, de que estos medicamentos no solo resultan dañinos sino que son benéficos, tampoco se aceptan todavía como agentes para la prevención o tratamiento de esta enfermedad o sus complicaciones.
32529643 Despite reports of neonatal COVID-19, SARS-CoV-2 has not been consistently isolated in perinatal samples thus, definitive proof of transplacental infection is still lacking. […] To address these questions, we assessed investigative tools used to confirm maternal-fetal infection and known protective mechanisms of the placental barrier that prevent transplacental pathogen migration. […] Histological examination demonstrated sparse viral particles, vascular malperfusion and inflammation in the placenta from pregnant women with COVID-19. […] The paucity of placental co-expression of ACE-2 and TMPRSS2, two receptors involved in cytoplasmic entry of SARS-CoV-2, may explain its relative insensitivity to transplacental infection. […] Viral interactions may utilise membrane receptors other than ACE-2 thus, tissue susceptibility may be broader than currently known. […] Further spatial-temporal studies are needed to determine the true potential for transplacental migration.
32531372 Participants from 2 large asthma cohorts were stratified using clinically relevant parameters to identify factors related to ACE2 expression within bronchial epithelium. […] ACE-2 correlated gene signatures were used to interrogate publicly available databases to identify upstream signaling events and novel therapeutic targets. […] 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.
32532937 SARS-CoV2 can reach the central nervous system from the bloodstream or olfactory pathway by binding ACE-2 receptor and the spike protein protease TMPRSS2.
32533988 Polymorphisms in ACE2 gene, ACE gene and in genes for some of the host cell proteases could affect the viral entry and replication.
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. […] Nevertheless, we hypothesized that a back load build up effect on Ang II may usurp the ACE capacity and subsequently leave the bradykinin system unabated. […] We think there are clinical clues for dry cough and the presumed aggravating role of ACE inhibitors like captopril on the disease process.
32538856 Fundació ACE is a non-profit organization providing care based on a holistic model to persons with cognitive disorders and their families for 25 years in Barcelona, Spain. […] We detail the sequence of events and the actions taken within Fundació ACE to swiftly adapt our face-to-face model of care to one based on telemedicine consultations. […] The total number of individuals being actively followed by Fundació ACE Memory Unit grew from 6,928 in 2017 to 8,147 in 2019. […] Weekly visits dropped by 60% following the suspension of face-to-face activity. […] We have shown that Fundació ACE model of care has been able to successfully adapt to a health and social critical situation as COVID-19 pandemic.
32542429 In this regard, we conducted a meta-analysis study of the prevalence of ACE (I/D) genotype in countries most affected by the COVID-19.
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. […] Moreover, many studies have shown the role of ACE in the development, severity, and complications of psoriasis. […] Herein, we discuss a possible shared mechanism of psoriasis with SARS-CoV-2; also, we propose a therapeutic approach to balance the effect of ACE activity in these patients.
32543705 Both, SARS CoV and SARS CoV-2 via their glycosylated spike proteins recognize the human angiotensin converting enzyme-2 (ACE-2) receptor. […] In the receptor binding domain (RBD), two sequence regions; “VGGNY” and “EIYQAGSTPCNGV” and a disulfide bridge connecting 480C and 488C in the extended loop are structural determinants for the recognition of human ACE-2 receptor.
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.
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). […] To date, no evidence shows that ACEIs or ARBs increase the susceptibility and mortality of patients infected with SARS-CoV-2, and hence, it is not advisable to discontinue such drugs in patients with cardiovascular disease.
32562397 Similar to the respiratory mucosa, angiotensin converting enzyme-2 (ACE-2) receptor and transmembrane serine protease 2 (TMPRSS2) co-express in the gastrointestinal tract, which facilitates viral entry into the tissue.
32562625 We present a case of acute Stanford type A aortic dissection in a patient with covid-19 under treatment of ACE inhibitors.
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.
32562764 Recent analysis concerning the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)- angiotensin converting enzyme (ACE) receptor interaction in enterocytes, the definition of gut-lung axis, as well as the molecular basis of sialic acid-related dual recognition concept in gastrointestinal SARS-CoV-2 infection, have brought a new perspective to potential therapeutic targets.
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. […] There is no clear evidence of a link between the use of medications such as ACE and ARB and an increased risk of SARS-Cov-2 infection. […] 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.
32564693 ACE (angiotensin-converting enzyme) inhibitors, diuretics, and β-blockers were more frequently used in nonsurvivors than in survivors.
32564694 We showed ACE (angiotensin-converting enzyme) 2 is higher in the kidney of male compared with female mice. […] 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.
32565763 The new virus infects and replicates in the lung parenchyma pneumocytes and macrophages in which the ACE-2 cell receptor resides.
32569491 The present research aimed to determine the relation between the use of angiotensin-converting enzyme inhibitors (ACE inh) and angiotensinogen receptor blockers (ARBs) and in-hospital mortality of hypertensive patients diagnosed with Covid-19 pneumonia. […] All patients were on ACE inh/ARBs or other antihypertensive therapy unless no contraindication was present. […] In total, 113 hypertensive Covid-19 patients were included, of them 74 patients were using ACE inh/ARBs. […] The frequency of admission to the ICU and endotracheal intubation were significantly higher in patients using ACE inh/ARBs. […] In a multivariable analysis, the use of ACE inh/ARBs was an independent predictor of in-hospital mortality (OR: 3.66; 95%CI: 1.11-18.18; p= .032). […] Kaplan-Meir curve analysis displayed that patients on ACE inh/ARBs therapy had higher incidence of in-hospital death than those who were not. […] The present study has found that the use of ACE inh/ARBs therapy might be associated with an increased in-hospital mortality in patients who were diagnosed with Covid-19 pneumonia. […] It is likely that ACE inh/ARBs therapy might not be beneficial in the subgroup of hypertensive Covid-19 patients despite the fact that there might be the possibility of some unmeasured residual confounders to affect the results of the study.
32573538 The review provides detailed literature data on drugs such as hydroxychloroquine / chloroquine, lopinavir/natinavir, remdesivir, ACE inhibitors and angiotensin converting enzyme receptor blockers, tissue plasminogen activator, as well as plasma transfusion transfusions.
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.
32575019 Pirfenidone could inhibit apoptosis, downregulate ACE receptors expression, decrease inflammation by several mechanisms and ameliorate oxidative stress and hence protect pneumocytes and other cells from COVID-19 invasion and cytokine storm simultaneously.
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. […] Our transcriptome sequencing studies on rat testicular germ cells showed ACE expression in rat testicular germ cells. […] 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.
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.
32582574 The angiotensin converting enzyme-2 (ACE-2) has been identified as the receptor for the SARS-CoV-2 viral entry. […] 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.
32583639 An unprotected person exposed to this cloud, might inhale a considerable amount of infectious viral doses, which will attach to the ACE 2 receptors on alveoli epithelium, resulting in infection.
32584199 The unintended consequences of the unprecedented scale and duration of pandemic control measures for children and families around the world should be carefully examined. 2019-nCoV, 2019 novel coronavirus; ADEM, acute demyelinating encephalomyelitis; AAP, American Academy of Pediatrics; ACE-2, angiotensin-converting enzyme 2; ARDS, acute respiratory distress syndrome; BCG, bacillus Calmette-Guérin; BNP, brain natriuretic peptide; CDC, Centers for Disease Control and Prevention; CRP, C-reactive protein; CSF, cerebrospinal fluid; COVID-19, coronavirus disease 2019; CT, computed tomography; CXR, chest X-ray; DOL, day of life; hCoV, human coronavirus; ICU, intensive care unit; IL, interleukin; IVIG, intravenous immunoglobulin; KD, Kawasaki disease; LDH, lactate dehydrogenase; MERS, Middle East respiratory syndrome; MERS-CoV, Middle East respiratory syndrome coronavirus; MEURI, monitored emergency use of unregistered and experimental interventions; MIS-C, multi-system inflammatory syndrome in children; PCR, polymerase chain reaction; PICU, paediatric intensive care unit; RNA, ribonucleic acid; RCT, randomised-controlled trial; RSV, respiratory syncytial virus; SARS, severe acute respiratory syndrome; SARS-CoV-1, severe acute respiratory syndrome coronavirus 1; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TNF-alpha, tumour necrosis factor alpha; UK United Kingdom; UNICEF, United Nations Children’s Fund; USA, United States of America; WHO, World Health Organization.
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.
32586380 The recent global pandemic has placed a high priority on identifying drugs to prevent or lessen clinical infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), caused by Coronavirus disease-2019 (COVID-19). […] 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 Various theories about drugs such as ACE inhibitors or angiotensin II receptor blockers (ARBs) in relation to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and clinical outcomes of COVID-19 are circulating in both mainstream media and medical literature. […] 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.
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). […] The role of angiotensin converting enzyme inhibitors (ACE) and angiotensin II receptor blockers (ARB) in COVID-19 is debated.
  1. does the regular use of angiotensin-converting enzyme inhibitors (ACE-i) or angiotensin-receptor blockers (ARB) make patients more likely to get infected and to die of Covid-19? […] With a necessary cautionary note that the evidence around the links between Covid-19 and cardiovascular disease is accruing at a fast pace, to date we can conclude that: (a) the greater susceptibility of individuals with underlying cardiovascular conditions to develop more severe Covid-19 with higher mortality rate is likely to be confounded, in part, by age and the type of co-morbidities. […] Patients with heart failure or chronic kidney disease might show an excess risk; (b) neither ACE-i nor ARB are associated with greater risk of SARS-Cov2 infection, or severity or risk of death in patients with Covid-19. […] Patients on these drugs should not stop them, unless under strict medical supervision and with the addition of a suitable replacement medicine.
32597315 Among the top results expected to bind with SARS-CoV-2 PLpro strongly were three cell protectives and antioxidants (NAD+, quercitrin, and oxiglutatione), three antivirals (ritonavir, moroxydine, and zanamivir), two antimicrobials (doripenem and sulfaguanidine), two anticancer drugs, three benzimidazole anthelmintics, one antacid (famotidine), three anti-hypertensive ACE receptor blockers (candesartan, losartan, and valsartan) and other miscellaneous systemically or topically acting drugs. […] The ten drugs with the highest estimated docking scores with favorable pharmacokinetics were subjected to molecular dynamics (MD) simulations followed by molecular mechanics/generalized Born surface area (MM/GBSA) binding energy calculations.
32597377 Angiotensin-converting enzyme 2 (ACE 2) is the entry receptor for the novel coronavirus SARS-CoV-2, the aetiological agent of COVID-19. […] At the same time, ACE 2 expression decreases during COVID-19. […] Two seemingly contradictory relationships between the expression of ACE 2 and COVID-19 have been reported. […] Increased level of expression of ACE 2 may be a risk factor for the development of COVID-19 infection, while reduced ACE 2 expression during COVID-19 leads to acute respiratory distress syndrome. […] This article provides a comprehensive overview of available scientific knowledge about the role of ACE 2 in the pathogenesis of COVID-19, which is available up to current day. […] Also, it discusses unknown factors that we will have to reveal in order to understand the whole role of ACE 2 in the pathogenesis of COVID-19.
32611305 Death from this disease has increased in patients who had with pre-existing medical conditions, especially cardiovascular ones, by eliminating the angiotensin-converting enzyme (ACE)-2 receptor in the lungs. […] 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.
32611676 It has been hypothesised that the use of ACE inhibitors and angiotensin receptor blockers (ARBs) might either increase or reduce the risk of severe or lethal COVID-19. […] We searched MedLine, Scopus and preprint repositories up to 8 June 2020 to retrieve cohort or case-control studies comparing the risk of severe/fatal COVID-19 (either mechanical ventilation, intensive care unit admission or death), among hypertensive subjects treated with: (1) ACE inhibitors, (2) ARBs and (3) both, versus untreated subjects. […] Compared with untreated subjects, those using either ACE inhibitors or ARBs showed a similar risk of severe or lethal COVID-19 (summary OR: 0.90; 95% CI 0.65 to 1.26 for ACE inhibitors; 0.92; 95% CI 0.75 to 1.12 for ARBs). […] The present meta-analysis strongly supports the recommendation of several scientific societies to continue ARBs or ACE inhibitors for all patients, unless otherwise advised by their physicians who should thus be reassured.
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. […] Community-based placebo-controlled trials of vitamin D supplementation may be difficult.
32619162 The second azurin derived peptide p28, fared the best among the docked proteins. p28 interacted with all the three viral proteins and the host ACE-2 receptor by forming several electrostatic and hydrogen bonds with the S-protein, 3CLpro, and PLpro. […] MD simulations indicated that p28 exhibited a strong affinity to S-protein and ACE-2 receptor, indicating a possibility of p28 as a protein-protein interaction inhibitor.
32621718 Effective ACE-II, GAK, AAK1, and protease 3C blockers can serve as a novel therapeutic approach to block the binding and attachment of the main COVID-19 protease (PDB ID: 6LU7) to the host cell and thus inhibit the infection at AT2 receptors in the lung.
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.
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. […] We found that the ACE1 II genotype frequency in a population was significantly negatively correlated with the number of SARS-CoV-2 cases. […] Similarly, the ACE1 II genotype was negatively correlated with the number of deaths due to SARS-CoV-2 infection. […] These data suggest that the ACE1 II genotype may influence the prevalence and clinical outcome of COVID-19 and serve as a predictive marker for COVID-19 risk and severity.
32633235 Dysfunction of the RAS has been observed in COVID-19 patients, but whether RAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs), are associated with improved or worse clinical outcomes, remains unclear. […] SARS-CoV-2 viral surface protein is known to attach angiotensin converting enzyme-2 (ACE-2) on the cell membrane to facilitate viral entry into the cytoplasm. […] 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. […] In this review we summarise the pathophysiology of the interaction between RAS, ACEIs/ARBs inhibitors and COVID-19, and conclude, on the basis of current data, that RAS blockade should be maintained during the current coronavirus pandemic.
32633718 Here, we present a novel molecular mechanism for COVID-19 that provides therapeutic intervention points that can be addressed with existing FDA-approved pharmaceuticals. […] 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 Intracerebral hemorrhage (ICH) is associated with old age and underlying conditions such as hypertension and diabetes. […] 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.
32634734 We review the interaction between viral corona spike protein and ACE-2 receptors present on the surface of alveolar lining cells, and contribution to hypercoagulabilty caused by the spike protein.
32635752 MERS coronavirus uses DPP4, while coronavirus HCoV-NL63 and SARS-CoV and SARS-CoV-2 employ ACE-2 as the key receptor.
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. […] ACE inhibitors (ACE-I) and Ang II type 1 receptor blockers (ARB), effective in cardiovascular diseases, were found to prevent and counteract acute lung injury in several experimental models by restoring the balance between these two opposing arms.
32643133 However, hypertension, coronary vascular disease, dyslipidemia, chronic kidney disease, diabetes, and history of taking angiotensin II receptor blockers (ARBs) or angiotensin-converting enzyme (ACE) inhibitors, as well as nonsteroidal anti-inflammatory drugs (NSAIDs), were not significantly associated with the death of COVID-19 patients.
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. […] ACE-Ang II-AT1R axis increases lipid storage, reduces white-to-beige fat conversion and plays role in obesity. […] ACE-Ang-II-AT1R axis, which has proinflammatory, profibrotic, prothrombotic and vasoconstrictive effects, is potential mechanism of more severe SARS-CoV-2 infection. […] 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.
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. […] Thus, some health care providers and media sources have questioned the continued use of ACE inhibitors and ARBs. […] In this brief review, we discuss the effect of ACE inhibitor-induced bradykinin on the cardiovascular system, on the renin-angiotensin-aldosterone system (RAAS) regulation in COVID-19 patients, and analyze recent clinical studies regarding patients treated with RAAS inhibitors.
32661494 Ergotamine, amphotericin b, and vancomycin are most promising to block the interaction of the SARS-CoV-2 S-protein with human ACE-2.
32664949 Angiotensin-converting enzyme (ACE)2 is a cellular receptor of SARS-CoV-2. […] 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.
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.
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.
32670680 As the coronavirus disease 2019 (COVID-19) pandemic evolves, more complications associated with the disease come to surface. […] Literature review shows that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) acts through angiotensin-converting enzyme 2 (ACE-2) receptors and causes cardiac injury by direct damage to the cardiomyocytes, systemic inflammation, fibrosis, interferon and cytokine-mediated immune response, coronary plaque destabilization, and hypoxia.
32670694 The first case was described in December 2019 in Wuhan, China, and by March 2020, most countries around the world have put in place some of the strictest restrictions seen in decades in order to slow down the spread of the disease. […] The proposed mechanism behind those associations is the expression of angiotensin converting enzyme II (ACE II) in those patients. […] Furthermore, the association between ACE inhibitors/AR blockers, which are among the most frequently prescribed medications, and serious cases of COVID 19 has been studied with the same mechanism in mind. […] The reports on the association between heart failure or coronary disease and COVID 19 are more uniform, and all seem to point to a greater risk from serious infections faced by patients with those comorbidities. […] A significant effort will need to be invested by the scientific community into finding strategies for protecting those patients from contracting the virus in the first place and then, once infected, into developing management plans aimed at preserving cardiac function as much as possible.
32673940 Extracellular matrix metalloproteinase inducer (EMMPRIN), which is also called BASIGIN/CD147, is a cell surface glycoprotein that belongs to the immunoglobulin superfamily and plays a significant role in intercellular recognition in immunology, cellular differentiation and development. […] Apart from ACE-2, recently EMMPRIN, has been regarded as a target for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) attachment and entry into the host cell. […] We proposed that in the ACE-2 depleted situation in OSCC, EMMPRIN receptor might get high jacked by the COVID-19 virus for the entry into the host cells.
32678588 After having performed electrostatic pKa calculations on several X-ray structures, we consider both the native (unbound) configuration of the enzyme and its noncovalent complex with a model peptide, Ace-Ala-Val-Leu-Gln∼Ser-Nme, which mimics the polyprotein sequence recognized at the active site.
32679185 SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE-2), a component of RAS, as a potential factor of cell penetration and infectivity; in addition, in the different infection stages, a functional variation of the RAS has been noted. […] In this article, we discuss the correlation between the role of RAS and system-modifying agents, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs) and direct renin inhibitors (DRIs), with SARS-CoV-2 infection.
32685191 There is current debate concerning the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II type 1 receptor blockers (ARBs), for hypertension management, during COVID-19 infection. […] 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. […] The factors contributing to acute kidney injury are diuretics, iodinated contrast administration, hemodynamic instability apart from ACE inhibitors, and angiotensin receptor blockers. […] The ACE inhibitors and ARBs were stopped in these patients due to acute kidney injury. […] We also discussed the role of ACE2 and the renin-angiotensin system (RAS) blockade in patients with COVID-19 infection along with pathogenesis.
32687917 The new SARS-CoV-2 virus reaches cells via ACE-2 and subsequently down-regulates ACE-2, leaving angiotensin II unbalanced in affected organs primarily in the lungs, heart, brain, and kidneys.
32691005 Research on many herbs-natural compounds also showed potent and significant inhibition of CoV-host protein pathways responsible for different phases of viral replication specifically targeting 3CLPRO, PLPRO, RdRp, helicase protein, S protein, N protein, 3a protein, Cathepsin L, Nsp1, Nsp3c, and ORF7a, and the S protein/ACE-2 interaction.
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. […] Further, in a re-analysis of clinical data from a meta-analysis of 9 studies, we show that ACEIs/ARBs usage was not associated with an increased risk of all-cause mortality. […] Literature suggests that ACEIs/ARBs usage generally appears to be clinically safe though their use in severe COVID-19 patients might increase the risk of acute renal injury. […] For definitive clarity, further clinical and mechanistic studies are needed in assessing the safety of all classes of ACE2 raising medications.
32703421 Previous work revealed that cellular uptake of SARS-CoV-2 requires Angiotensin Converting Enzyme 2 (ACE-2) and a cellular protease. […] The spike (S) protein on SARS-CoV-2 binds ACE-2, which functions as an entry receptor.
32708430 It invades the cell at the angiotensin converting enzyme-2 (ACE-2) receptor and binds to hemoproteins, resulting in a severe systemic inflammatory response, particularly in high ACE-2 organs like the lungs, heart, and kidney, resulting in systemic disease. […] This is further complicated by genetic polymorphisms of CYP2D6, HO-1, ACE, and ACE-2.
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.
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. […] There may be massive derangement of the entire RAS after the attack of COVID-19 and hence, patients with these pre-existing comorbidities and on ACE inhibitors or angiotensin receptor blockers should be monitored carefully considering the role of RAS in the prognosis of COVID-19 infections.
32715080 SARS-CoV-2 infects host cells through ACE2 receptors, leading to COVID-19-related pneumonia. […] The continuation of clinically indicated ACE inhibitor and ARB medications is recommended in COVID-19.
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.
32721804 It is based on the inhibition of Spike glycoprotein and ACE-2 receptor interaction that provides the entry of virus in human host cells, by targeting the S protein with a recombinant molecule made of the ACE-2 receptor ectodomain and an opsonin, the formed complex would enhance its phagocytosis.
32721809 Since, children had been known to be less severely affected by the virus in part due to the higher concentration of Angiotensin converting enzyme (ACE)-2 receptor, this presentation has emerged concerns regarding the infection of children with SARS-COV2. […] 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.
32724306 The role of diabetes mellitus in molecular processes including augmenting Angiotensin-Converting Enzyme 2 (ACE 2) levels is also discussed as potential mechanisms to explain the grave prognosis seen in these patients.
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. […] Thus, the role of ACE inhibitors or angiotensin receptor blockers may play a critical role in the severity or outcome of disease. […] 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.
32729826 From March 2019 to March 2020, there was a 39% increase in angiotensin II antagonist prescriptions, a 33% increase in lipid-lowering drug prescriptions, a 32% increase in calcium channel blocker (CCB) prescriptions, a 30% increase in beta blocker prescriptions, a 27% increase in angiotensin-converting enzyme (ACE) inhibitor, vitamin k antagonist (VKA), and oral antidiabetic prescriptions, a 24% increase in diuretic prescriptions, and an 18% increase in insulin prescriptions.
32730512 In the classical pathway, the angiotensin converting enzyme (ACE) generates Angiotensin II (AngII), which is powerfully inflammatory and vasoconstrictive. […] 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.
32731090 Underlying immunosuppression, elevated cytokine levels, altered expression of the angiotensin converting enzyme (ACE-2) and TMPRSS2, and a prothrombotic status may fuel the effects of a SARS-CoV-2 in some cancer patients, but have the potential to be used as biomarkers for severe disease and therapeutic targets.
32735768 We also investigated if these drugs directly interact with Angiotensin-Converting Enzyme (ACE 2), which is a crucial component of the virus entry to the cells.
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. […] Considering that the ACE insertion (I)/deletion (D) gene polymorphism contributes to the ACE level variability in general population, in which mean ACE level in DD carriers is approximately twice that in II carriers, we propose a hypothesis of genetic predisposition to severe lung injury in patients with coronavirus disease 2019. […] It is plausible that the ACE inhibitors and ACE receptor blockers may have the potential to prevent and to treat the acute lung injury after SARS-CoV-2 infection, especially for those with the ACE genotype associated with high ACE level.
32737124 There is uncertainty about the associations of angiotensive enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) drugs with COVID-19 disease. […] We used Cox proportional hazards models to derive adjusted HRs for exposure to ACE inhibitor and ARB drugs adjusted for sociodemographic factors, concurrent medications and geographical region. […] ACE inhibitors were associated with a significantly reduced risk of COVID-19 disease (adjusted HR 0.71, 95% CI 0.67 to 0.74) but no increased risk of ICU care (adjusted HR 0.89, 95% CI 0.75 to 1.06) after adjusting for a wide range of confounders. […] Adjusted HRs for ARBs were 0.63 (95% CI 0.59 to 0.67) for COVID-19 disease and 1.02 (95% CI 0.83 to 1.25) for ICU care.There were significant interactions between ethnicity and ACE inhibitors and ARBs for COVID-19 disease. […] The risk of COVID-19 disease associated with ACE inhibitors was higher in Caribbean (adjusted HR 1.05, 95% CI 0.87 to 1.28) and Black African (adjusted HR 1.31, 95% CI 1.08 to 1.59) groups than the white group (adjusted HR 0.66, 95% CI 0.63 to 0.70). […] ACE inhibitors and ARBs are associated with reduced risks of COVID-19 disease after adjusting for a wide range of variables. […] Neither ACE inhibitors nor ARBs are associated with significantly increased risks of receiving ICU care. […] Variations between different ethnic groups raise the possibility of ethnic-specific effects of ACE inhibitors/ARBs on COVID-19 disease susceptibility and severity which deserves further study.
32737423 The fact that the virus uses angiotensin-converting enzyme (ACE)-2 as the cell entry receptor and that hypertension as well as cardiovascular disorders frequently coexist with COVID-19 have generated considerable discussion on the management of patients with hypertension. […] Summarizing what is known and what requires further investigation in this field may help to address the challenges we face. […] 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. […] Finally, we review evidence on the use of antihypertensive medication, namely, ACE inhibitors and angiotensin receptor blockers, in patients with COVID-19.
32737584 One such event left SARS-CoV-2 with a receptor binding domain (RBD) capable of binding the human ACE-2 receptor lacking in RaTG13, and a second event uniquely added to SARS-CoV-2 a site specific for furin, capable of efficient endoproteolytic cleavage and activation of the spike glycoprotein responsible for virus entry and cell fusion.
32740406 The primary objective of this study is to determine the effect of baseline use of angiotensin-converting enzyme inhibitor (ACE-i)/AT1 blocker (ARB) on mortality in hospitalized coronavirus disease 2019 (Covid-19) African-American patients. […] The secondary objectives are, to determine the effect of baseline use of ACE-i/ARB on the need for mechanical ventilation, new dialysis, ICU care, and on composite of above-mentioned outcomes in the same cohort. […] Patients were divided into two groups, those on ACE-i/ARB at baseline and those not on them. […] Out of 531 patients included in the analysis, 207 (39%) were on ACE-i/ARB at baseline. […] Patients in ACE-i/ARB group were older (64 vs. 57 years, P < 0.001), and had higher prevalence of hypertension (96.6 vs. […] Baseline use of ACE-i/ARB does not worsen outcomes in hospitalized Covid-19 African-American patients.
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. […] However, this aspect has raised many concerns about the use of ACE inhibitors or ARBs in infected patients or patients at risk of infection. […] 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. […] Therefore, ACE inhibitors or angiotensin receptor blocker drugs should be continued in infected patients, as their discontinuation can increase Ang II activity and induce injury to the lungs or cardiovascular system.
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. […] Our objective is to explore what is known and unknown about the role of ACE inhibitors and ARBs in COVID-19 patients. […] Early studies from China which speculated on the role of ACE inhibition and ARBs did not evaluate the drug regimens. […] A vast body of evidence supports the use of ACE inhibitors and ARBs in hypertensive patients and patients with heart failure, and very little evidence has been acquired about their role in COVID-19. […] There is good evidence in support of the use of ACE inhibitors and ARBs in indicated patients with hypertension and heart failure, and clinicians should be reticent about abruptly withdrawing these drugs based on a paucity of evidence.
32748812 Bioinformatic analysis of the DNA sequence encoding the SARS-CoV-2 cell receptor angiotensin-converting enzyme 2 (ACE-2) was performed to identify consensus motifs for transcription factors mediating cellular response to pollutant insult. […] The bioinformatic analysis of the ACE-2 gene identified nine putative consensus motifs for the aryl hydrocarbon receptor (AHR). […] Our results confirm the supposed link between air pollution and the rate and outcome of SARS-CoV-2 infection and support the hypothesis that pollution-induced over-expression of ACE-2 on human airways may favor SARS-CoV-2 infectivity.
32755325 The CB could be a site of SARS-CoV-2 invasion, due to local expression of its receptor [angiotensin-converting enzyme (ACE) 2] and an alternative route of nervous system invasion, through retrograde transport along the carotid sinus nerve. […] The CB function could be affected by COVID-19-induced inflammatory/immune reactions and/or ACE1/ACE2 imbalance, both at local or systemic level.
32755836 The genome phylogenetic analysis suggested that genomic sequence of SARS-CoV-2 is almost 80% similar to that of SARS-CoV, further both these viruses bind to same host cell receptor ACE-2.
32757246 An association among the use of angiotensin converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) with the clinical outcomes of coronavirus disease 2019 (COVID-19) is unclear. […] PubMed, EMBASE, MedRxiv, and BioRxiv were searched for relevant studies that assessed the association between application of ACEI/ARB and risk of COVID-19, inflammation level, severity COVID-19 infection, and death in patients with COVID-19. […] ACEI/ARB therapy might be associated with the reduced inflammatory factor (interleukin-6) and elevated immune cells counts (CD3, CD8). […] Meta-analysis showed no significant increase in the risk of COVID-19 infection (odds ratio [OR]: 0.95, 95%CI: 0.89-1.05) in patients receiving ACEI/ARB therapy, and ACEI/ARB therapy was associated with a decreased risk of severe COVID-19 (OR: 0.75, 95%CI: 0.59-0.96) and mortality (OR: 0.52, 95%CI: 0.35-0.79). […] Subgroup analyses showed among the general population, ACEI/ARB therapy was associated with reduced severe COVID-19 infection (OR: 0.79, 95%CI: 0.60-1.05) and all-cause mortality (OR: 0.31, 95%CI: 0.13-0.75), and COVID-19 infection (OR: 0.85, 95% CI: 0.66-1.08) were not increased. […] Among patients with hypertension, the use of an ACEI/ARB was associated with a lower severity of COVID-19 (OR: 0.73, 95%CI: 0.51-1.03) and lower mortality (OR: 0.57, 95%CI: 0.37-0.87), without evidence of an increased risk of COVID-19 infection (OR: 1.00). […] On the basis of the available evidence, ACEI/ARB therapy should be continued in patients who are at risk for, or have COVID-19, either in general population or hypertension patients.
32758625 Thus, the use of ACE inhibitors or angiotensin receptor blockers could worsen the glucose level in patients suffering from novel coronavirus infection.
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.
32758873 Resolving this paradox requires looking beyond the binary model of a viral receptor-binding domain (RBD) attaching to the ACE-2 receptor. […] A NCBI pBlast analysis revealed that the SARS-CoV-2 surface spike protein contains key two calcium-dependent fusion domains that are almost identical to those that were recently discovered SARS-CoV-1. […] These viral calcium-dependent binding domains can facilitate membrane fusion only after cleavage by the host surface protease TMPRSS2.
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.
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. […] BPP-10c strongly decreases angiotensin II by inhibiting ACE, increasing bradykinin-related effects on the bradykinin 2-receptor and increasing nitric oxide-mediated effects.
32764454 On the other hand, it has been reported that SARS-CoV-2 spike (S) protein binds to angiotensin-converting enzyme 2 (ACE-2), that promotes cellular entry of this virus in concert with host proteases, principally transmembrane serine protease 2 (TMPRSS2). […] We herein provide a comprehensive and up-to-date overview of the role of ACE-2 and TMPRSS2 genes, as key entry elements as well as therapeutic targets for SARS-CoV-2 infection, which can help to better understand the applications and capacities of various remedial approaches for infected individuals, especially those with lung cancer.
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). […] Moreover, there is evidence that ACE genotype affects the outcomes of acute respiratory distress syndrome (ARDS) treatment, the most severe consequence of SARS-CoV-2 infection. […] COVID-19 morbidity, infection course, and mortality might depend on ACE D allele frequency. […] The aim of this narrative review was to analyze and identify the mechanisms of ACE-I and ARBs with particular emphasis on angiotensin receptors and their polymorphism in the light of COVID-19 pandemic as these medications are commonly prescribed to elderly patients. […] There is no direct evidence yet for ACE-I or ARBs in the treatment of COVID-19. […] However, for those already taking these medications, both the European Society of Cardiology and the American College of Cardiology recommend continuing the treatment, because at present, there is no clear clinical or scientific evidence to justify the discontinuation of ACE-I or ARBs.
32765938 Because, COVID-19 shows its effect through ACE-2 and adipose tissue is very rich and important tissue in terms of ACE-2.
32766285 Background: Cardiometabolic morbidity and medications, specifically Angiotensin Converting Enzyme inhibitors (ACEi) and Angiotensin Receptor Blockers (ARBs), have been linked with adverse outcomes from coronavirus disease 2019 (COVID-19). […] We considered the following exposures: age, sex, ethnicity, body mass index (BMI), diabetes, hypertension, hypercholesterolaemia, ACEi/ARB use, prior myocardial infarction (MI), and smoking. […] ACE/ARB use did not associate with COVID-19 status.
32768223 With a focus on felines, we review here the evidence for SARS-CoV-2 infection in cats, ferrets and dogs, describe the relationship between SARS-CoV-2 and the natural coronaviruses known to infect these species, and provide a rationale for the relative susceptibility of these species to SARS-CoV-2 through comparative analysis of the ACE-2 receptor.
32768709 The evaluations in this retrospective cross-sectional study are based on the IMS RPM® (Regional Pharmaceutical Market) Weekly database, which shows the weekly purchases of public pharmacies from fully-stocked wholesalers at the time the pharmacy purchase is made in Germany. […] The increase was 43% for vitamin k antagonists, 39% for ACE inhibitors, and 37% for betablockers.
32769024 A multiplexed solid-phase chemiluminescence assay (Meso Scale Discovery) was evaluated for the simultaneous detection of IgG binding to four SARS-CoV-2 antigens and the quantification of antibody-induced ACE-2 binding inhibition (pseudo-neutralisation assay).
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. […] In the current study we demonstrated by bioinformatics (CASTp: computed atlas of surface topography of protein, PyMol: molecular visualization) and molecular docking (PatchDock and Autodock) experiments that tea flavonoids catechin products mainly epigallocatechin gallate or other like theaflavin gallate demonstrated higher atomic contact energy (ACE) value, binding energy, Ki value, ligand efficiency, surface area and more amino acid interactions than hydroxychloroquine (HCQ) during binding in the central channel of the spike protein. […] 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.
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). […] In the central nervous system (CNS), ACE mediates neuroinflammation, neurodegeneration and neurotoxicity responsible for several CNS disorders. […] 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.
32778033 Angiotensin converting enzyme 2(ACE2) as a component of the RAS system. […] However, unlike the ACE, its activity is not inhibited by the ACE inhibitors. […] 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.
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.
32788073 SARS-CoV-2 utilizes ACE-2 receptors found at the surface of the host cells to get inside the cell. […] Certain comorbidities are associated with a strong ACE-2 receptor expression and higher release of proprotein convertase that enhances the viral entry into the host cells.
32791137 The spike protein of SARS-CoV-2 binds to angiotensin-converting enzyme-2 (ACE-2) receptors and enter the host cells. […] Several reports have been highlighted the importance of ACE-2 on the pathogenesis of COVID-19. […] In the present study, we hypothesize that a functional insertion/deletion polymorphism in the ACE gene could be associated with SARS-CoV-2 infection and mortality. […] PubMed and Google scholar search engines were used to obtained data on the prevalence of ACE I/D polymorphism in different countries of the Asia continent. […] Epidemiological investigation revealed a significant positive correlation of D allele of ACE polymorphism with SARS-CoV-2 infection (r = 0.502, p = 0.008, n = 26) and mortality rate (r = 0.620, p = 0.002, n = 22) in Asian population. […] However, no significant role of ACE I/D polymorphism was observed with recovery rate of patients from SARS-CoV-2 infection (r = -0.208, p = 0.352, n = 22). […] Allele D of ACE insertion/deletion polymorphism is associated with the rate of infection and mortality in the Asian population.
32799423 In this study, the effect of commonly used medications on the expression of SARS-CoV-2 receptor, angiotensin-converting enzyme (ACE)2, and TMPRSS2 protein in kidney tissues was evaluated. […] 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.
32799894 The virus enters the cell by attaching its spike-like surface projections to the angiotensin-converting enzyme-2 (ACE-2) expressed in various tissues.
32803688 ACE-2 is shown to be the cellular host receptor for SARS-CoV-2.
32807512 Mechanism of diarrhea is thought to be related to direct viral cytotoxicity occurring when the SARS-CoV-3 enters GI cells via the ACE-2 receptor.
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.
32819226 In this aspect, our objective was to screen essential flavonoids against possible protein targets such as SARS-CoV-2 spike glycoprotein receptor binding domain (RBD-S) and host Angiotensin Converting Enzyme-2 protease domain (PD-ACE-2) using in silico molecular docking studies. […] The flavonoids that passed Lipinski rule were subjected to in silico analysis through molecular docking on RBD-S and PD-ACE-2 using Molegro Virtual Docker v6.0. […] In silicoanalysis reported that biochanin A and silymarin bind significantly at the active sites of RBD-Sand PD-ACE-2 with a MolDock score of -78.41and -121.28 kcal/mol respectively. […] The current outcomes created a new paradigm in understanding biochanin A and silymarin bioflavonoids as potent inhibitors of RBD-Sand PD-ACE-2 targets respectively, further work can be extended to confirm their therapeutic potential in COVID-19.
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. […] Because ACE receptor is also present in the endothelium of other districts as well as in different cell types, and as porphyrins are transporters in the blood and other biological liquids of iron forming heme, which is important in the assembly of the hemoglobin, myoglobin and the cytochromes, multiorgan damage occurs both primitive and secondary to lung damage.
32835018 The present short report summarizes some clinical characteristics of six patients affected by stroke while being on angiotensin-converting enzyme (ACE)2 inhibitors and angiotensin II receptor blockers (ARBs) before and during COVID-19. […] Medical charts and images of six patients affected by stroke while being on ACE-Is and ARBs therapy before and during COVID-19 outbreak in Lombardy region, Italy, were reviewed. […] All patients showed clinical features typical of SARS-CoV-2 infection and positive chest CT scan, and were treated with ACE-Is as needed. […] An urgent need of randomized clinical trials aimed to assess the safety profile and neuroprotective properties of ACE-Is and ARBs in COVID-19 patients diagnosed with stroke does exists.
32835160 While scientist are working to find a vaccine, current epidemiological data shows that the most common comorbidities for patients with the worst prognosis, hypertension and diabetes, are often treated with angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). […] Both ACE inhibitors and ARBs induce overexpression of the angiotensin converting enzyme 2 (ACE-2) receptor, which has been identified as the main receptor used by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to enter into the alveolar cells of the lungs. […] While cannabinoids are known to reduce hypertension, the studies testing the hypotensive effects of cannabinoids never addressed their effects on ACE-2 receptors. […] Since there are around 192 million people using cannabis worldwide, we believe that the mechanism underlying the hypotensive properties of cannabinoids should be urgently studied to understand if they can also lead to ACE-2 overexpression as other antihypertensive drugs do.
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 There is ongoing debate about whether the use of angiotensin converting enzyme (ACE) inhibitors (ACEi) and angiotensin receptor blockers (ARBs) are useful or hazardous in patients with COVID-19, with both narratives supported by researchers with different hypotheses. […] 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.
32837207 Several pathophysiological mechanisms are involved, including decreased renal perfusion related to mechanical ventilation, sepsis and cytokines release, as well as direct virus toxicity on proximal tubular cells and podocytes, mediated by angiotensin 2 conversion receptors (ACE 2) and TMPRSS proteases. […] More than 20 % of ICU COVID-19 patients require extra renal replacement therapy (ERT) for acute renal failure that is made difficult by the hypercoagulable state of these patients, responsible for filter thrombosis.
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.
32838138 Amid of coronavirus disease 2019 (Covid-19) pandemic, much emphasis was initially placed on the elderly or those who have preexisting health conditions such as obesity, hypertension, and diabetes as being at high risk of contracting and/or dying of Covid-19. […] While it is still too early to determine why the gender gap is emerging, this article point to several possible factors such as higher expression of angiotensin-converting enzyme-2 (ACE 2; receptors for coronavirus) in male than female, sex-based immunological differences driven by sex hormone and X chromosome. […] Irresponsible attitude among men reversibly affect their undertaking of preventive measures such as frequent handwashing, wearing of face mask, and stay at home orders.
32838195 Despite the burden of disease of CVD and DM, there is a lack of experimentally validated literature exploring their association with exacerbation of COVID-19. […] Firstly, AMPK mediated phosphorylation of ACE-2 by metformin as well as the drug’s alkaline properties may interrupt the natural disease progression. […] Finally, recent studies have shown that statins’ ability to inhibit the cytokine storm may outweigh concerns of statin mediated ACE-2 upregulation in COVID-19.
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. […] We reviewed current literature about the potential association between the utilization of RAS inhibitors, namely angiotensin-converting enzyme inhibitors (ACE-inhibitors) and angiotensin-receptor blockers (ARBs) and likelihood of developing severe COVID-19 infection and whether or not continuation of these medications is appropriate in patients with active disease. […] The joint statement from the American College of Cardiology (ACC), American Heart Association (AHA), European Society of Cardiology (ESC) and Heart Failure Society of America (HFSA), strongly recommends that physicians should not initiate or withdraw their usual RAS-related treatments (ACE-inhibitor/ARB) to COVID-19 infected patients with cardiovascular disease.
32844337 Given that cardiovascular diseases (CVD) are the leading cause of morbidity around the world and that several trials have reported severe cardiovascular damage in patients infected with SARS-CoV-2, a substantial number of COVID-19 patients with underlying cardiovascular diseases need to continue their medications in order to improve myocardial contractility and to prevent the onset of major adverse cardiovascular events (MACEs), including heart failure. […] 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.
32846165 The main cause of diarrhea was found to be invasive by SARS-CoV-2 of ACE-2-expressing epithelial cells of the small intestine, causing local intestinal damage.
32848272 The endemic human coronavirus NL63 strain (HCoV-NL63) employs angiotensin-converting enzyme 2 (ACE-2) receptors on cell surfaces to infect hosts in the same manner as SARS-CoV and the novel SARS-CoV-2. […] It has been proposed that patients on angiotensin-converting enzyme inhibitor (ACE-I) and angiotensin receptor blockers (ARB) therapy infected with SARS-CoV-2 have a higher mortality rate due to over-expression of ACE-2 receptors. […] We sought to evaluate the impact of ACE-I/ARB on infectivity of various endemic coronavirus strains, hypothesizing that rates of ACE-I use among patients with HCoV-NL63 would be higher compared to other endemic coronavirus strains that do not utilize the ACE-2 receptor. […] Rate of ACE-I/ARB use among each coronavirus strain and clinical outcomes from the 88 HCoV-NL63 positive subjects was collected. […] Analysis revealed a higher rate of ACE-I (p=0.006) use among the HCoV-NL63 positives compared to the other three endemic coronavirus strains. […] The rate of invasive mechanical ventilation (p=0.007) and 90-day mortality (p=0.045) among HCoV-NL63 positives on ACE-I therapy was higher compared to those HCoV-NL63 positives not on ACE-I therapy. […] Concurrent therapy with an ACE-I was associated with an increased rate and severity of infection with the HCoV-NL63.
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. […] Antiviral medication (lopinavir, darunavir, favipiravir, remdesivir, ribavirin, oseltamivir, tocilizumab, and umifenovir), ACE inhibitors, interferon-α2b, co-therapy with azithromycin, inhaling iNO, and oxygen therapy can be used for treatment.
32848790 Interestingly, some products may block the ACE-2 receptor or the serine protease TMPRRS2 required by SARS-CoV-2 to infect human cells.
32849666 Angiotensin-Converting-Enzyme (ACE) 2 displays lung protective effects: it inactivates DABK and converts Angiotensin II (Ang II) into Angiotensin-(1-7) and Angiotensin I into Angiotensin-(1-9). […] 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.
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. […] Some authors proposed the discontinuation of ACEIs and ARBs for cardiovascular, kidney, and metabolic diseases, while expert opinions have discouraged that due to limited empirical evidence of their negative effect on COVID-19 outcomes, and that withdrawing treatment may contribute to clinical decompensation in high-risk patients. […] Moreover, as cardiovascular and metabolic diseases are associated with neurodegenerative and psychiatric disorders, especially among older adults, a critical appraisal of the potential positive effects of ACEIs and ARBs is highly needed. […] Herein, we aim to discuss the conundrum of ACEIs and ARBs use in high-risk patients for COVID-19, and their potential protective role on the development and/or progression of geriatric neuropsychiatric disorders.
32850973 Since virus binding to ACE-2 alone could not be sufficient to justify such severe infection, in order to facilitate medical countermeasure development and to search for new targets, two further regions of S protein have been taken into consideration here. […] We propose that a cooperating therapy using inhibitors against multiple targets altogether i.e., ACE2, integrins and sugars could be definitely more effective.
32851855 The magnitude of the outbreak and the potentially severe clinical course of COVID-19 has led to a burst of scientific research on this novel coronavirus and its host receptor ACE (angiotensin-converting enzyme)-2. […] 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.
32853230 Previous use of ACE inhibitors had no effect on risk of death (HR 0.97, 95% CI 0.69 to 1.34).
32862840 CLQ-OH molecules are shown to saturate virus attachment sites on gangliosides in the vicinity of the primary coronavirus receptor, angiotensin-converting enzyme-2 (ACE-2).
32864784 Based on recent evidence, the angiotensin-converting enzyme (ACE) II is known to be the target of the COVID-19 spike protein, which enables the virus to penetrate human cells. […] ACE II also possesses an anti-inflammatory role in many pathologies such as cardiovascular disease, hypertension, diabetes mellitus and other conditions, which are the main risk factors of poor prognosis in COVID-19 infection. […] Changes in tissue ACE II levels are associated with many diseases and hyperinflammatory states, and it is assumed that elevated levels of ACE II could aggravate the course of COVID-19 infection.
32866536 Similar to SARS coronavirus, the pulmonary angiotensin converting enzyme (ACE) 2 was introduced as the virus receptor for entering the cell. […] In this study, vitamin D, ACE concentrations, and neutrophil to lymphocyte ratio (NLR) were measured in patients with confirmed COVID-19 in comparison with control group. […] Results demonstrated significant alterations in vitamin D and ACE levels as well as NLR in the patients’ group.
32868092 In addition to therapeutics, concern was raised over potential risks associated with ACE inhibitors and ARB use, which is presented.
32869673 The viral spike coat protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) engages the human ACE (angiotensin-converting enzyme) 2 cell surface receptor to infect the host cells. […] Thus, concerns arose regarding theoretically higher risk for coronavirus disease-19 (COVID-19) in patients taking ACE inhibitors/angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]). […] After pooling the adjusted odds ratios from the included studies, no significant increase was noted in the risk of SARS-CoV-2 infection by the use of ACE inhibitors (adjusted odds ratio, 0.95 [95% CI, 0.86-1.05]) or ARBs (adjusted odds ratio, 1.05 [95% CI, 0.97-1.14]). […] However, the random-effects meta-regression revealed that age may modify the SARS-CoV-2 infection risk in subjects with the use of ARBs (coefficient, -0.006 [95% CI, -0.016 to 0.004]), that is, the use of ARBs, as opposed to ACE inhibitors, specifically augmented the risk of SARS-CoV-2 infection in younger subjects (<60 years old). […] The use of ACE inhibitors might not increase the susceptibility of SARS-CoV-2 infection, severity of disease, and mortality in case-population and cohort studies. […] Additionally, we discovered for the first time that the use of ARBs, as opposed to ACE inhibitors, specifically augmented the risk of SARS-CoV-2 infection in younger subjects, without obvious effects on COVID-19 outcomes.
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.
32873147 Angiotensin Converting Enzyme (ACE) inhibitors are widely used as a first line medication for the treatment of hypertension in the UK, although their use was suggested in early reports to increase the risk associated with SARS-CoV-2 infection. […] Demographic and other baseline data were extracted from electronic case records, and patients grouped depending on ACE inhibitor usage or not. […] Of these 27 (30.7%) used ACE inhibitors. […] This study contributes to the growing evidence supporting the continued use of ACE inhibitors in COVID-19 disease, although adequately powered randomised controlled trials will be needed to confirm effects.
32875490 Coronavirus disease 2019 (COVID-19) is due to severe acute respiratory syndrome coronavirus (SARS-CoV)-2 which binds and enters the host cells through the angiotensin-converting enzyme (ACE)2. […] 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.
32881654 The overactivation of the ACE/Ang II/AT1R axis and the enhancement of inflammation contribute to deleterious effects of COVID-19.
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 performed a differential expression analysis in order to identify differentially expressed genes in COVID-19 patients correlated with ACE-2 and we explored their direct relations with a network approach integrating also drug-gene interactions. […] We found 825 differentially expressed genes correlated with ACE2.
32892687 SARS-CoV-2 utilizes metallocarboxyl peptidase angiotensin receptor (ACE) 2 to gain entry into human cells. […] 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.
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.
32901433 Regression analysis correlated presence of ACE insertion/deletion (I/D) polymorphism to COVID-19 incidence and mortality. […] Furthermore, COVID-19 prevalence correlated to allele frequency of angiotensin-converting enzyme (ACE) deletion (D) polymorphism within the European population. […] Homozygous ACE deletion polymorphism is associated with increase in ACE and angiotensin II (Ang-II), sustained levels can result in inflammation, fibrosis and organ damage. […] The ACE DD polymorphism is also associated with hypertension, acute respiratory distress and diabetic nephropathy, all considered high risk for COVID-19 infection and outcomes. […] The study objective was to describe a biological framework associating ethnic prevalence of ACE deletion polymorphism to COVID-19 comorbidities providing rationale for therapeutic utility of ACE-I/ARBs to improve outcomes. […] The Allele Frequency Database (ALFRED) was queried for frequency of rs4646994 representing ACE I/D polymorphism. […] In a total of 349 worldwide population samples, frequency of ACE D allele was higher in European, Asian, and Africans cohorts. […] In the USA, the frequency of ACE D allele was higher in non-Hispanic Black compared with non-Hispanic White and Mexican Americans. […] COVID-19 binding mediated reduction/inactivation of ACE-II can increase ACE/Ang-II signalling pathway and related pathologies. […] The presence of ACE DD polymorphism with COVID-19 infection likely augments ACE/Ang-II activities, increasing severity of COVID-19 morbidities and impacts outcomes. […] Thus, ethnic prevalence of ACE DD polymorphism can explain in part the severity of COVID-19 morbidity providing rationale for the use of ACE-I/ARBs to improve outcomes.
32903640 Besides, the treatment regime involves drugs like losartan, ACE inhibitors, angiotensin-receptor blockers, Remdesivir, Chloroquine, Hydroxychloroquine, etc. may modulate the severity of the comorbidities.
32904621 This research aimed to explore the effect of adverse childhood experience (ACE) on suicide ideation in young cancer patients during the COVID-19 pandemic. […] Self-reported questionnaires analyzed the mediating effects of sleep quality, anxiety symptoms, and inflammatory conditions between ACE and suicide ideation. […] Correlation analysis and structural equation model were used to explore the relationships between ACE, sleep quality, anxiety symptom, serum C-reactive protein (CRP) levels and suicide ideation. […] The mediating roles of sleep quality, anxiety symptoms, and CRP levels on the influence of ACE on suicide ideation were explored. […] ACE was positively related to anxiety symptoms, CRP levels, and suicide ideation, and negatively related to sleep quality. […] From these results, we found ACE affected suicide ideation directly and was mediated by roles sleep quality, anxiety symptom and CRP. […] ACE not only directly affected suicide ideation but also affected suicide ideation through sleep quality, anxiety symptoms, and inflammatory conditions in young cancer patients during the COVID-19 pandemic. […] Therefore, targeted intervention and help for cancer patients from the perspective of ACE should be put into practice.
32905551 Background and objective Angiotensin-converting enzyme inhibitors (ACE) and angiotensin II receptor blockers (ARB) are commonly used for the treatment of patients with heart disease, hypertension (HTN), and diabetes mellitus (DM). […] 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. […] We conducted a single-center retrospective study to evaluate the association of in-patient use of ACE/ARB with outcomes among a predominantly ethnic minority patient population of the inner New York City (NYC). […] Results Of the 469 patients included in the study, 91 patients (19.4%) used ACE/ARB therapy during their hospital stay and were labeled as ACE/ARB group. […] Patients in the ACE/ARB therapy group were older and had a higher incidence of HTN, coronary artery disease (CAD), congestive heart failure, DM, asthma, and chronic obstructive pulmonary disease. […] Admission D-dimer, lactate dehydrogenase (LDH), and C-reactive protein (CRP) levels were similar between the two groups, but absolute lymphocyte count (ALC) was lower in the non-ACE/ARB group (0.971 k/ul vs. […] Univariate analysis by treatment group using the log-rank test produced significant results (p=0.0062), indicating a higher survival rate for the ACE/ARB group. […] Conclusion The use of ACE/ARB appears to be safe in all patients in whom their use is medically indicated.
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. […] Both 2D:4D and the ACE I/D polymorphism are covariates of oxygen metabolism. […] Here, we examine the interrelationships between 2D:4D, ACE polymorphism, and COVID-19 CFR. […] National frequencies/rates were obtained for 2D:4D from the BBC Internet study (n = 41), published values of ACE I/II (n = 39), and COVID-19 CFR from three World Health Organization situation reports (n = 41). […] 2D:4D was negatively associated with national ACE I/II frequencies. […] The relationships between ACE I/II and CFR were non-significant. […] Relationships between male 2D:4D and CFR’s were independent of female 2D:4D and ACE I/II. […] The ACE I/D polymorphism may influence 2D:4D such that ACE II individuals have lower 2D:4D than ACE DD individuals. […] Low 2D:4D and ACE II individuals show efficient oxygen metabolism. […] Therefore, low 2D:4D and ACE II together may protect against COVID-19 severity. […] 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.
32909060 Sustentacular cells showing ACE-2 immunohistochemical expression 200 to 700 times greater than nasal or tracheal epithelia seem to be the main SARS-CoV-2 gateway.
32910274 While the COVID-19 pandemic is constantly evolving, it remains unclear whether the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) affects the clinical course of SARS-CoV-2 infection. […] For this meta-analysis, PubMed, CENTRAL, and grey literature were searched from their inception to 19 May 2020 for randomized, controlled trials or observational studies that evaluate the association between the use of either ACE inhibitors or ARBs and the risk for major clinical endpoints (infection, hospitalization, admission to ICU, death) in adult patients during the COVID-19 pandemic. […] ACE inhibitors and ARBs were not associated with increased odds for SARS-CoV-2 infection, admission to hospital, severe or critical illness, admission to ICU, and SARS-CoV-2-related death. […] In Asian countries, the use of ACE inhibitors/ARBs decreased the odds for severe or critical illness and death (OR = 0.37, 95% CI 0.16-0.89, I2 = 83%, and OR = 0.62, 95% CI 0.39-0.99, I2 = 0%, respectively), whereas they increased the odds for ICU admission in North America and death in Europe (OR = 1.75, 95% CI 1.37-2.23, I2 = 0%, and OR = 1.68, 95% CI 1.05-2.70, I2 = 82%, respectively). […] ACE inhibitors might be marginally protective regarding SARS-CoV-2-related death compared with ARBs (OR = 0.86, 95% CI 0.74-1.00, I2 = 0%). […] Randomized controlled trials are needed to confirm the aforementioned associations between ACE inhibitors, ARBs, and SARS-CoV-2.
32910704 However, ACE-2 plays a common role in the pathogenesis of adipocyte hypertrophy and COVID 19. […] 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.
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. […] While presently it is advised that patients should continue to use ACE inhibitors or angiotensin receptor blockers, questions still remain as to whether adverse effects are potentiated by the virus. […] Here, we report a case of a 57-year-old man, unknowingly with COVID-19, who presented to the emergency department with tongue swelling, shortness of breath and difficulty in speaking following 4 months taking benazepril, an ACE inhibitor.
32916821 Smoking can upregulate the angiotensin-converting enzyme-2 (ACE-2) receptor utilized by SARS-CoV-2 to enter the host cell and activate a ‘cytokine storm’ which can lead to worsen outcomes in COVID-19 patients.
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).
32917504 We hypothesized that the renal abundance of angiotensin-converting enzyme (ACE) 2, the cell surface receptor for SARS-CoV-2, may be modulated by diabetes and agents that block the renin-angiotensin-aldosterone system (RAAS). […] The expression of ACE 2 was examined in 49 archival kidney biopsies from patients with diabetic kidney disease and from 12 healthy, potential living allograft donors using next-generation sequencing technology (RNA Seq). […] Mean ACE 2 messenger RNA was increased approximately 2-fold in diabetes when compared with healthy control subjects (mean ± SD, 13.2±7.9 vs 7.7±3.6 reads per million reads, respectively; p=0.001). […] Increased ACE 2 messenger RNA in the diabetic kidney may increase the risk and/or severity of kidney infection with SARS-CoV-2 in the setting of COVID-19 disease.
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.
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.
32922174 In addition, melatonin is an inhibitor of calmodulin, an essential intracellular component to maintain angiotensin-converting enzyme 2 (ACE-2) on the cell surface. […] Consequently, melatonin can have response potential in early stages for its possible effects on ACE-2 and Mpro, although it is also promising in more severe stages of the disease for its action against hyper-inflammation.
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.
32926920 In December 2019, a novel virus, namely COVID-19 caused by SARS-CoV-2, developed from Wuhan, (Hubei territory of China) used its viral spike glycoprotein receptor-binding domain (RBD) for the entrance into a host cell by binding with ACE-2 receptor and cause acute respiratory distress syndrome (ARDS).
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. […] The most frequently examined drugs were angiotensin receptor blockers (ARBs) (n=55) and ACE inhibitors (ACE-I) (n=22). […] More studies reported upregulation than downregulation with ACE-I (n=22), ARBs (n=55), insulin (n=8), thiazolidinedione (n=7) aldosterone agonists (n=3), statins (n=5), oestrogens (n=5) calcium channel blockers (n=3) glucagon-like peptide 1 (GLP-1) agonists (n=2) and Non-steroidal anti-inflammatory drugs (NSAIDs) (n=2). […] There is an abundance of the academic literature and media reports on the potential of drugs that could attenuate or exacerbate COVID-19 disease. […] 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.
32943474 One of the postulated mechanisms for this high fatality rate is the possible abundance of ACE type 2 receptor in the cardiovascular system that strongly binds with the spike protein of COVID-19 and helps internalise into the cell resulting in acute cardiac injury (ACI).
32945216 The use of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) in patients with coronavirus disease 2019 (COVID-19) given their interaction with the angiotensin-converting enzyme-2 (ACE-2) receptor remains controversial. . […] To investigate the impact of ACEI/ARB on COVID-19 disease severity and mortality through a systematic review and meta-analysis. […] We searched PubMed and CINAHL databases as well as pre-print servers for studies investigating usage of ACEIs/ARBs in patients with COVID-19 compared to a control group of COVID-19 patients without ACEI/ARB use. […] For mortality with ACEI/ARB use, the pooled odds ratio was 1.29 [0.89-1.87] p = 0.18 with heterogeneity of 91%, while the pooled OR for COVID-19 severity was 0.94 [0.59-1.50] p = 0.81 with heterogeneity of 89% (Figure 2). […] Even on pooled analysis of both un-adjusted data, adjusted data(studies with matched controls) and taking into account factors such as risk of bias of studies via meta regression and sensitivity analyses, the results hold true that ACEI/ARB use is not associated with COVID-19 disease severity or mortality. […] To look for any potential beneficial effects, randomized controlled trials are needed. use of ACEI/ARB was not associated with increased mortality or severe COVID-19.
32947136 Furthermore, studies have indicated that the spike proteins of SARS-CoV-2 use the Angiotensin Converting Enzyme-2 (ACE-2) receptor for its attachment similar to SARS-CoV-1, which is followed by priming of spike protein by Transmembrane protease serine 2 (TMPRSS2) which can be targeted by a proven inhibitor of TMPRSS2, camostat.
32947193 SARS-CoV-2 mainly invades respiratory epithelial cells by adhesion to angiotensin-converting enzyme 2 (ACE-2) and thus, infected patients may develop mild to severe inflammatory responses and acute lung injury.
32950697 The virus crossed the species barrier and established in the human population taking advantage of the spike protein high affinity for the ACE receptor to infect the lower respiratory tract. […] Strikingly, genomes with the conserved position D614 were almost completely replaced by genomes with the G614 substitution between March to April 2020. […] A similar replacement pattern was observed with R203K/G204R although more marked in Chile, Argentina and Brazil, suggesting similar introduction history and/or control strategies of SARS-CoV-2 in these countries.
32956644 In this regard, some medication being tested in clinical trials and in vitro studies include anti-viral RNA polymerase inhibitors, HIV-protease inhibitors, anti-inflammatory agents, angiotensin converting enzyme type 2 (ACE 2) blockers, and some other novel medications.
32957905 Among the 5 selected epitopes, the peptide LRARSVSPK can be the most potent epitope because of its high geometric shape complementarity score, low ACE and very high response to it by the world population (81.81% global population coverage).
32958395 There was no significant difference between the antibody-positive subjects and the antibody-negative subjects in any background factors investigated including overseas travel, contact with overseas travelers, presence/absence of infected individuals in the living area, use of trains 5 times a week or more, BCG vaccination, and use of ACE inhibitor and ARB.
32963099 The membrane-anchored spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a pivotal role in directing the fusion of the virus particle mediated by the host cell receptor angiotensin-converting enzyme 2 (ACE-2).
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.
32967179 In depth search and analysis revealed several medicinal plants with excellent efficacy against SARS-CoV-1 and MERS-CoV, which are well-known to act on ACE-2 receptor, 3CLpro and other viral protein targets.
32971153 The use of angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and non-steroidal anti-inflammatory drugs (NSAIDs) was common (37.5%, 25% and 18.8% respectively). […] Other features of patients with diabetes and COVID-19 infection included long duration of diabetes, less tight glycaemic control and common use of ACE inhibitors, ARBs and NSAIDs.
32980434 There is a great deal of debate about the role of cardiovascular comorbidities and the chronic use of antihypertensive agents (such as ACE-I and ARBs) on mortality on COVID-19 patients. […] Of note, ACE2 is responsible for the host cell entry of the virus. […] The aim of the study was to evaluate the role of chronic treatment with ACE-I or ARBs and other clinical predictors on in-hospital mortality in a cohort of COVID-19 patients. […] Multivariate analysis showed that a chronic intake of ACE-I was associated with a trend in reduction of mortality (OR: 0.53; 95% CI: 0.27-1.03; p = 0.06), differently from a chronic intake of ARB (OR: 1.1; 95% CI: 0.5-2.8; p=0.8).
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. […] As COVID-19 spans multiple organ systems linked to the cardiovascular system, it is imperative to understand clearly how severe acute respiratory syndrome coronavirus 2 may affect the multifaceted RAS. […] 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).
32981754 AA, and other BALs influence cell membrane fluidity and thus, regulate ACE-2 (angiotensin converting enzyme-2) receptors (the ligand through which SARS-CoV2 enters the cell) receptors.
32982622 This phenomenon could be explained by the overexpression of the angiotensin converting enzyme 2 (ACE-2) on epithelial cell surfaces of the respiratory tract. […] Indeed, ACE-2 is a receptor for coronaviruses including the severe acute respiratory syndrome coronavirus 1 and 2 (SARS-CoV), and ACE-2 is overexpressed under chronic exposure to air pollution such as NO2 and PM2.5. […] In this review, we explain that ACE-2 acts as the sole receptor for the attachment of the SARS-CoV-2 via its spike protein. […] The fact that respiratory and vascular epithelial cells express ACE-2 has been previously observed during the 2003 epidemic of the SARS-CoV-1 in China, and during the 2012 Middle East respiratory syndrome in Saudi Arabia. […] High ACE-2 expression in respiratory epithelial cells under air pollution explains the positive correlation between the severity in COVID-19 patients and elevated air pollution, notably high NO2 and PM2.5 levels. […] Overall, we demonstrate a link between NO2 emissions, PM2.5 levels, ACE-2 expression and COVID-19 infection severity. […] Therefore, air pollution should be reduced in places where confirmed cases of COVID-19 are unexpectedly high.
32983259 Genes co-expressed with ACE2 were considered potential therapeutic targets on COVID-19. […] The top ten core targets are EGFR, CASP3, STAT3, ESR1, FPR2, F2, BCL2L1, BDKRB2, MPO, and ACE.
32986671 Fundació ACE is a research center and memory clinic based in Barcelona, Spain, one of the hardest-hit countries. […] A total of 130 patients were participating in 16 active clinical trials in Fundació ACE when the lockdown was established. […] The plan implemented by Fundació ACE was able to preserve safety and integrity of ongoing clinical trials.
32990314 Angiotensin-converting enzyme (ACE) is a zinc membrane metallopeptidase that plays a key role in regulating vasoactive peptide levels and hence cardiovascular activity through its conversion of angiotensin I (Ang I) to Ang II and its metabolism of bradykinin. […] 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.
32991879 SARS-CoV-2 penetrates host cells through the angiotensin 2 conversion enzyme (ACE-2). […] ACE-2 is expressed not only in the lungs, but also in other organs, including the cardiovascular system. […] Pathological remodeling of the extracellular matrix caused by viral infection leads to myocardial fibrotic lesions.
32992048 The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received angiotensin-converting-enzyme inhibitors (ACE-I) or angiotensin-receptor blockers (ARB) with patients who did not. […] Out of 4,069 COVID-19 patients, 13.5% and 13.3% received ACE-I or ARB, respectively. […] Use of neither ACE-I nor ARB was associated with mortality (multivariable hazard ratio (HR) adjusted also for COVID-19 treatments: 0.96, 95% confidence interval 0.77-1.20 and HR=0.89, 0.67-1.19 for ACE-I and ARB, respectively). […] Findings were similar restricting the analysis to hypertensive (N=2,057) patients (HR=1.00, 0.78-1.26 and HR=0.88, 0.65-1.20) or when ACE-I or ARB were considered as a single group. […] In this observational study and meta-analysis of the literature, ACE-I or ARB use was not associated with severity or in-hospital mortality in COVID-19 patients.
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. […] Other drugs that are more likely to present clinical effects despite the lack of specific evidence for COVID-19 include anti-androgens (spironolactone, eplerenone, finasteride and dutasteride), statins, N-acetyl cysteine (NAC), ACE inhibitors (ACEi), angiotensin receptor blockers (ARB), and direct TMPRSS-2 inhibitors (nafamostat and camostat).
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. […] Furthermore, respiratory epithelia were negative for ACE-2 and TMPRSS2 protein expression while positive for BSG and furin, suggesting a possible alternative entry route for SARS-CoV-2.
32994260 Over a 3-month period we aim to recruit a minimum of 500 patients across 10 hospital sites, collecting baseline data including: patient demographics; presence of comorbidities; relevant blood tests on admission; prescription of ACE inhibitors/angiotensin receptor blockers/non-steroidal anti-inflammatory drugs/immunosuppressants; smoking status; Clinical Frailty Score (CFS); length of hospital stay; mortality and readmission.
32994678 Comparative molecular docking and vixualization analysis of the human thrombin with the SARS CoV-2 Spike glycoprotein and the human ACE-2 receptors is of interest. […] The data shows that residues spanning positions 30-41 in the ACE-2 have interaction with the spike glycoprotein (UniProt ID: Q9BYF1). […] Results also shows that thrombin binds with SER494 in the spike protein, and GLU37 in the ACE2 receptor.
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. […] Breakthrough discoveries also took place, with other RAAS endopeptides being described, including alamandine and angiotensin A.
32998607 Background Angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) may worsen the prognosis of coronavirus disease 2019, but any association could be confounded by the cardiometabolic conditions indicating ACE-I/ARB use. […] We therefore examined the impact of ACE-Is/ARBs on respiratory tract infection outcomes. […] Thirty-day mortality and risk of admission to the intensive care unit in ACE-Is/ARBs users was compared with nonusers and with users of calcium channel blockers. […] Of 568 019 patients hospitalized with influenza or pneumonia, 100 278 were ACE-I/ARB users and 37 961 were users of calcium channel blockers. […] In propensity score-weighted analyses, ACE-I/ARB users had marginally lower 30-day mortality than users of calcium channel blockers (13.9% versus 14.5%; RD, -0.6%; 95% CI, -1.0 to -0.1; RR, 0.96; 95% CI, 0.93-0.99), and a lower risk of admission to the intensive care unit (8.0% versus 9.6%; RD, -1.6%; 95% CI, -2.0 to -1.2; RR, 0.83; 95% CI, 0.80-0.87). […] Compared with nonusers, current ACE-I/ARB users had lower mortality (RD, -2.4%; 95% CI, -2.8 to -2.0; RR, 0.85; 95% CI, 0.83-0.87), but similar risk of admission to the intensive care unit (RD, 0.4%; 95% CI, 0.0-0.7; RR, 1.04; 95% CI, 1.00-1.09). […] Conclusions Among patients with influenza or pneumonia, ACE-I/ARB users had no increased risk of admission to the intensive care unit and slightly reduced mortality after controlling for confounding.
33000221 It is now well‑established that entry of SARS‑CoV‑2 into host cells is facilitated by its spike proteins mainly through binding to the angiotensin‑converting enzyme 2 (ACE‑2).
33001409 A significant univariate association between age; sex; body mass index; smoking; diabetes; cardiovascular, pulmonary, neurological, and kidney diseases; ACE inhibitor therapy; statin intake and an increased risk for complicated clinical stages of COVID-19 at diagnosis was found.
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.
33007400 The main cell receptor targeted is the surface-bound ACE-2.
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. […] In this literature, we reviewed several studies to evaluate the relevance between SARS-CoV-2, ACE receptor, and female and male reproductive system and found that the risk of being attacked by SARS-CoV-2 is higher in males than in females.
33009727 Notably, ACE-2 plays the same role in both cases and a similar geographical distribution is observed in both diseases.
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. […] ACE 2 is almost 100-fold higher in kidneys than lung, and the virus can also involve the kidney in the same manner.
33015550 Angiotensin-converting enzyme-2 (ACE-2), a potential receptor for SARS-CoV-2 entry, is expressed on various brain cells and cerebral parts, i.e., subfornical organ, paraventricular nucleus, nucleus of the tractus solitarius, and rostral ventrolateral medulla, as well as in non-cardiovascular areas such as the motor cortex and raphe. […] The resident CNS cells like astrocytes and microglia also express ACE-2, thus highlighting the vulnerability of the nervous system to SARS-CoV-2 infection.
33015748 Although COVID-19 is predominantly a respiratory illness, other systems including gastrointestinal (GI) system and liver may be involved because of the ubiquitous nature of ACE-2 receptors in various cell lines that SARS-CoV-2 utilizes to enter host cells.
33015836 We have identified 28 novel peptides and molecular docking study revealed that some peptides showed strong binding potential to insulin receptor and ACE. […] Thus, these peptides might be used to manage diabetes complication as well as COVID-19 disease due to their interaction with ACE.
33023356 Background SARS-CoV-2 (COVID-19) utilizes the angiotensin converting enzyme-2 (ACE-2) receptor to enter human cells. […] Angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor antagonists (ARB) are associated with ACE-2 upregulation. […] We hypothesized that antecedent use of ACEI/ARB may be associated with mortality in COVID-19. […] Among these 781 acutely ill patients, 133 (17.0%) used an ARB and 171 (21.9%) used an ACEI. […] While neither sex nor smoking status differed by user groups, patients on ACEI/ARB tended to be older and more likely to have hypertension, diabetes mellitus, and congestive heart failure. […] The crude odds ratios (ORs) for death for ACEI users and ARB users were 0.98, 95% confidence interval (CI): 0.60-1.60, p=0.9333, and 1.13, 95% CI: 0.67-1.91, p=0.6385, respectively. […] After adjusting for age, hypertension, diabetes mellitus, and congestive heart failure, antecedent ACEI administration was associated with reduced mortality (OR: 0.55, 95% CI: 0.31-0.98, p=0.0436); a similar, but weaker trend was observed for ARB administration (OR: 0.58, 95% CI: 0.32-1.07, p=0.0796). […] Conclusions In those aged ≥50 years hospitalized with COVID-19, antecedent use of ACEI was independently associated with reduced risk of inpatient death.
33025553 Angiotensin-converting enzyme 2 (ACE-2) is the receptor for cellular entry of SARS-CoV-2. […] ACE-2 is a type I transmembrane metallo-carboxypeptidase involved in the Renin-Angiotensin pathway. […] By analyzing two independent databases, ACE-2 was identified in several human tissues including the thyroid. […] Although some cases of COVID-19-related subacute thyroiditis were recently described, direct proof for the expression of the ACE-2 mRNA in thyroid cells is still lacking. […] Aim of the present study was to investigate by RT-PCR whether the mRNA encoding for ACE-2 is present in human thyroid cells. […] The ACE-2 mRNA was detected in all surgical thyroid tissue samples (n = 15). […] Compared with two reporter genes (GAPDH: 0.052 ± 0.0026 Cycles-1; β-actin: 0.044 ± 0.0025 Cycles-1; ACE-2: 0.035 ± 0.0024 Cycles-1), the mean level of transcript expression for ACE-2 mRNA was abundant. […] The expression of ACE-2 mRNA in follicular cells was confirmed by analyzing primary cultures of thyroid cells, which expressed the ACE-2 mRNA at levels similar to tissues. […] The results of the present study demonstrate that the mRNA encoding for the ACE-2 receptor is expressed in thyroid follicular cells, making them a potential target for SARS-COV-2 entry.
33025652 Angiotensin-converting enzyme 2 (ACE 2) is the binding domain for severe acute respiratory syndrome coronavirus (SARS-CoV) and SARSCoV-2. […] 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). […] Genetically predicted effects of ACE inhibitors increased lymphocyte percentage (0.78, 95% confidence interval [CI] 0.35, 1.22), decreased neutrophil percentage (-0.64, 95% CI -1.09, -0.20) and possibly lowered TNF-α (-4.92, 95% CI -8.50, -1.33). […] 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.
33039120 Angiotensin converting enzyme (ACE) type 2 is the receptor of SARSCoV-2 for cell entry into lung cells. […] Because ACE-2 may be modulated by ACE inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), there are concern that patients treated with ACEIs and ARBs are at higher risk for COVID-19 infection or severity. […] This study sought to analyse the association of severe forms of COVID-19 and mortality with hypertension and a previous treatment with ACEI and ARB. […] Mortality and severe COVID-19 (criteria: death, intensive care unit, or hospitalisation >30 days) were compared in patients receiving or not ACEIs and ARBs. […] The association between ACEI/ARB treatment and COVID-19 severity criteria found in univariate analysis (Odds Ratio 1.74, 95%CI [1.14-2.64], P=0.01) was not confirmed when adjusted on age, gender, and hypertension (adjusted OR1.13 [0.59-2.15], P=0.72). […] This study suggests that previous treatment with ACEI and ARB is not associated with hospital mortality, 1- and 2-month mortality, and severity criteria in patients hospitalised for COVID-19. […] No protective effect of ACEIs and ARBs on severe pneumonia related to COVID-19 was demonstrated.
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.
33042157 SARS-CoV-2 replication in ACE-2-expressing pneumocytes can drive the diffuse alveolar injury through the cytokine storm and immunothrombosis by upregulating the transcription of chemokine/cytokines, unlike several other respiratory viruses.
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). […] Thus, the understanding of SARS-CoV-2 intracellular pathways and interactions with the RAS may clarify COVID-19 physiopathology and open perspectives for new treatments and strategies.
33043967 In this prospective single-center study, we determined the serum levels of ACE-2, angiotensin II and aldosterone in patients with COVID-19 compared to control patients presenting with similar symptoms in the emergency unit. […] Mean serum concentrations of ACE2, angiotensin II, and aldosterone did not differ between the SARS-CoV-2 positive and the control group.
33046644 As coronaviruses cause severe economic losses in the pork industry and swine are key intermediate hosts of human disease outbreaks, we synthetically resurrected a recombinant virus (rSADS-CoV) as well as a derivative encoding tomato red fluorescent protein (tRFP) in place of ORF3. rSADS-CoV replicated efficiently in a variety of continuous animal and primate cell lines, including human liver and rectal carcinoma cell lines. […] Of concern, rSADS-CoV also replicated efficiently in several different primary human lung cell types, as well as primary human intestinal cells. rSADS-CoV did not use human coronavirus ACE-2, DPP4, or CD13 receptors for docking and entry.
33049279 The primary target of the SARS-CoV-2 virus is the human lungs governed by the ACE-2 receptor of epithelial type II cells/endothelial cells, which promote modulation of the immune response of host cells through generating cytokine storm, inflammation, severe pneumonia symptoms, and secondary complications such as acute respiratory distress syndrome. […] Mesenchymal stem cells own self-renewal, differentiation, homing, immunomodulation and remains unaffected by the coronavirus on the virtue of the absence of ACE-2 receptors, indicating that MSC’s could be used an ameliorative approach for COVID-19.
33052313 Moreover, the docking on mucin as well as various receptors including Angiotensin-converting enzyme 2 (ACE-2), heparin sulphate proteoglycan and Phosphatidylinositol binding clathrin assembly protein (PICALM), which are expressed in the lung and intranasal tissues and represent initial sites of attachment of the viral particles to the surface of respiratory cells, has shown good binding of CQ and HCQ to these receptors.
33059711 In phase 1, SARS-CoV-2 binds with angiotensin converting enzyme (ACE)2 receptor on alveolar macrophages and epithelial cells, triggering toll like receptor (TLR) mediated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ƙB) signaling.
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. […] The expression of ACE increased rapidly after birth and reached a peak on day 21 after birth (P<0.05). […] 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.
33063823 The virulence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the aggressive nature of the disease has transformed the universal pace of research in the desperate attempt to seek effective therapies to halt the morbidity and mortality of this pandemic. […] 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.
33065163 Angiotensin converting enzyme (ACE)-2 is a modulator of adipose tissue metabolism. […] However, human data of adipose ACE-2 is rarely available. […] Considering that, ACE-2 is believed to be the receptor responsible for cell entry of SARS-CoV-2, a better understanding of its regulation is desirable. […] We therefore characterized the modulation of subcutaneous adipose ACE-2 mRNA expression during weight loss and the impact of ACE-2 expression on weight loss induced short- and long-term improvements of glucose metabolism. ) was measured in subcutaneous adipose tissue before and after weight loss. (p = 0.011). […] Our data indicate that subcutaneous adipose ACE-2 expression correlates with insulin sensitivity. […] Weight loss induced decline of subcutaneous adipose ACE-2 expression might affect short- and long-term improvement of myocellular insulin sensitivity, which might be also relevant in the context of ACE-2 downregulation by SARS-CoV-2.
33065388 Molecular mechanics-generalized Born surface area energy calculations revealed greater salvianolic acid A affinity for the enzyme over curcumin and lopinavir with energies of -44.8, -34.2 and -34.8 kcal/mol, respectively. […] Using a STRING database, protein-protein interactions were identified for salvianolic acid A included the biochemical signaling genes ACE, MAPK14 and ESR1; and for curcumin, EGFR and TNF.
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. […] However, the usage of ACE-2 inhibitors to block the SARS-CoV-2 viral entry requires additional studies as there are conflicting findings and severe health complications reported for these inhibitors in patients.
33078221 Here, we evaluated a novel flow cytometric approach to assess spike-specific antibody responses.HEK 293T cells expressing SARS-CoV-2 spike protein in its natural confirmation on the surface were used to detect specific IgG and IgM antibody responses in patient sera by flow cytometry. […] A soluble angiotensin-converting-enzyme 2 (ACE-2) variant was developed as external standard to quantify spike-specific antibody responses on different assay platforms.
33078484 We discuss the role myocardial microvascular pericytes expressing the ACE-2 receptor and their potential for an organ-specific cardiac involvement with COVID-19.
33080435 COVID-19 is associated with the different comorbidities with its change in biological function such as causing heart dysfunction via deregulating ACE-2 receptor, gastrointestinal risk via causing vomiting, diarrhea, and abdominal pain, chronic kidney disease via proteinuria and hematuria, diabetes mellitus, liver injury via increasing ALT, AST and bilirubin level, lung injury, CNS risk, ocular risk, and cancer risk. […] The disturbed IL-4 decreases the level of the ACE-2 with the inflammation.
33082849 Angiotensin converting enzyme-2 (ACE-2) mediated cellular entry of SARS-Cov2 leads to receptor shedding of ACE-2 and disrupts the renin angiotensin aldosterone axis (RAAS). […] ACE-2 downregulation causes bradykinin accumulation which may exert its proliferative action via mitogen activated protein kinase pathways which has established roles in cancers of breast and kidney.
33086161 Regarding susceptibility, Non-O individuals have Anti-A antibodies which can prevent viral entry across ACE-2 receptors, moreover, Non-O individuals are at higher risk of autoimmunity, hypercoagulable state, and dysbiosis resulting in an augmented tendency for vascular inflammatory sequelae of COVID-19. […] On a therapeutic level, plasma from normal O blood group individuals might potentially replace the use of convalescent serum for the treatment of COVID-19.
33089707 The viruses associated with COVID-19 like that of SARS enters the body via the ACE-2 receptors in the central nervous system, which causes the body to balance an immune response against potential damage to nonrenewable cells.
33091758 Moreover, angiotensin-converting enzyme 2 (ACE-2) acts as a functional receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and male hormones are effective in the ACE-2 passageway and simplify SARS-CoV-2 entry into host cells.
33093981 The angiotensin-converting enzyme (ACE) II receptor is expressed in circumventricular organs and in cerebrovascular endothelial cells, which play a role in vascular autoregulation and cerebral blood flow. […] For this reason, is rational the hypothesize that brain ACE II could be involved in COVID-19 infection.
33097184 A critical step of the infection cycle is the binding of the virus spike S protein to the cellular ACE-2 receptor. […] This interaction involves a receptor binding domain (RBD) located at the center of the S trimer, whereas the lateral N-terminal domain (NTD) displays a flat ganglioside binding site that enables the virus to bind to lipid rafts of the plasma membrane, where the ACE-2 receptor resides.
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.
33106765 Allopathic treatments inhibit viral infection by targeting majorly endocytosis, and angiotensin-converting enzyme (Ace) receptor signaling.
33108836 There is established evidence of COVID-19 blood viremia, a viral pathogenic cycle via angiotensin-converting enzyme 2 (ACE-2) receptors and similar blood transmission risk data from the SARS (severe acute respiratory syndrome)/MERS (Middle East respiratory syndrome) era. […] Based on the evidence, there is an established additional risk of viral transmission faced by surgical teams from blood-aerosols generated from the operative wound of COVID-19- infected patients via the inhalation of virus-laden aerosols and the subsequent initiation of the viral pathogenic cycle through binding with pulmonary ACE-2 receptors.
33111329 Data are lacking on the impact of ACEI/ARB exposure on unfavorable outcome in the population of patients hospitalized for COVID-19 with hypertension/cardiovascular disease, particularly in Europe. […] The ACE-CoV study was designed to assess this question. […] ACEI/ARB exposures at admission were assessed. […] Among them, 111 were included in the ACE-CoV study population. […] In OW-PS-adjusted analyses, the association of exposure to ACEIs or ARBs with outcome occurrence was OR: 1.56 (95% CI: 0.73-3.33). […] It was 0.99 (95% CI: 0.68-1.45) for ACEIs and 1.64 (95% CI: 0.77-3.50) for ARBs. […] The ACE-CoV study found no association between exposure to ACEIs or ARBs and unfavorable outcome in hospitalized patients for COVID-19 with a history of cardiovascular disease/arterial hypertension.
33112637 Hence, the need to combine anti-inflammatory agents such as interferons, angiotensinogen converting enzyme (ACE) 2 inhibitors, interleukin- 6 (IL-6), and Janus kinase (JAK) family inhibitors, anticoagulants and other agents involved in inflammation resolution.
33114370 Furthermore, pharmacological profiles of ACE inhibitors and their impurities were determined via an in silico approach.
33116037 Uncertainty and apprehension are exacerbated in people using angiotensin-converting enzyme (ACE) inhibitors to control their comorbidities such as hypertension and diabetes. […] 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. […] Amiloride, a prototypic inhibitor of epithelial sodium channels (ENaC) can be an ideal candidate for COVID-19 patients, given its ACE reducing and cytosolic pH increasing effects.
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.
33123031 Angiotensin (Ang)-converting enzyme (ACE) 2 is a key component in COVID-19 infection. […] 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.
33126657 Later, augmented angiotensin converting enzyme (ACE) 2 activity supposedly helps to attenuate inflammation. […] 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.
33129880 Angiotensin-converting enzyme 2 (ACE 2) is a membrane-bound enzyme that cleaves angiotensin II (Ang II) into angiotensin (1-7). […] ACE 2 is abundantly present in the intestine, kidney, heart, lungs, and fetal tissues. […] Fetal ACE 2 is involved in myocardium growth, lungs and brain development. […] ACE 2 is highly expressed in pregnant women to compensate preeclampsia by modulating angiotensin (1-7) which binds to the Mas receptor, having vasodilator action and maintain fluid homeostasis. […] There are reports available on Zika, H1N1 and SARS-CoV where these viruses have shown to produce fetal defects but very little is known about SARS-CoV-2 involvement in pregnancy, but it might have the potential to interact with fetal ACE 2 and enhance COVID-19 transmission to the fetus, leading to fetal morbidity and mortality. […] This review sheds light on a path of SARS-CoV-2 transmission risk in pregnancy and its possible link with fetal ACE 2.
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.
33138658 SARS-CoV-2 enters the cell by binding to the ACE II receptor and begins viral replication. […] However, the effects on the pancreas-another organ that also expresses ACE II-have not been studied.
33139081 The Acute Care for Elders (ACE) is a model of care addressed to reduce the incidence of loss of self-care abilities of older adults occurring during hospitalization for acute illness. […] This observational study aimed to describe the effectiveness of an ACE unit at a long-term care facility to prevent functional decline (decrease in the Barthel Index score of >5 points from admission to discharge) in older adults with frailty (Clinical Frailty Scale score ≥5) and symptomatic COVID-19. […] An ACE unit at a long-term care facility constitutes an alternative to hospital care to prevent hospital-associated disability for frail older patients with COVID-19.
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.
33145103 The functional receptor to SARS-CoV-2, the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic, is angiotensin-converting enzyme-2 (ACE-2), the same enzyme that physiologically counters the renin-angiotensin system (RAS) activation. […] Some researchers have questioned RAS inhibitors’ safety in COVID-19 patients since these drugs have demonstrated an increase in ACE-2 expression in preclinical studies; therefore, they may facilitate viral invasion.
33146362 Gastrointestinal symptoms were also more prevalent among patients on chronic immunosuppressants, ACE/ARB medications, and patient with chronic kidney disease (p<0.05).
33146371 Angiotensin converting enzyme (ACE) is well-known for its role in blood pressure regulation via the renin-angiotensin aldosterone system (RAAS) but also functions in fertility, immunity, haematopoiesis and diseases such as obesity, fibrosis and Alzheimer’s dementia. […] 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. […] This, in turn, has enabled the development of ACE inhibitors for the treatment of cardiovascular disease and candidate therapies for the treatment of COVID-19. […] However, despite these advances the function of ACE homologues in non-human organisms is not yet fully understood. […] ACE homologues have been discovered in the tissues, body fluids and venom of species from diverse lineages and are known to have important functions in fertility, envenoming and insect-host defence mechanisms. […] We, therefore, further highlight the need for structural insight into insect and venom ACE homologues for the potential development of novel anti-venoms and insecticides.
33147503 SARS-CoV-2 utilizes the ACE-II receptor (Angiotensin-converting enzyme II receptor) on epithelial cells for its entry and replication. […] Activation of the ACE-II receptor is indirectly associated with the activation of S1P Receptor 1 signaling which is associated with IL-6 driven fibrosis.
33151050 Formalin-fixed paraffin-embedded tissues were stained with hematoxylin and eosin (H&E) and subjected to immunofluorescence for angiotensin-converting enzyme 2 (ACE-2) expression. […] Immunofluorescent stained slides from six COVID-19 positive men demonstrated a direct association between increased quantitative ACE-2 levels and impairment of spermatogenesis. […] The novel COVID-19 has an affinity for ACE-2 receptors. […] Since ACE-2 receptor expression is high in the testes, we hypothesized that COVID-19 is prevalent in testes tissue of infected patients. […] We found an inverse association between ACE-2 receptor levels and spermatogenesis, suggesting a possible mechanism of how COVID-19 can cause infertility.
33152916 In this review efforts are made to expand understanding and explain the possible roles of the immune system, the sex hormones and the angiotensin-converting enzyme (ACE) systems in male bias to severe COVID-19. […] Also, this review explores possible therapeutic avenues including androgen deprivation therapy (ADT), estrogen-based therapy, and ACE inhibitors for consideration in the fight against COVID-19.
33154144 We aimed to estimate the association of RAAS inhibitors, including ACE inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) with COVID-19 mortality risk in patients with hypertension. […] Studies reporting the association of RAAS inhibitors (ACEi or ARBs) and mortality in patients with hypertension, hospitalised for COVID-19 were extracted.
33155953 Due to its antiandrogenic effects, spironolactone can inhibit X-chromosome-related synthesis of ACE-2 receptors and activation of transmembrane serin protease 2.
33160938 Spike glycoprotein is one of such potential drug target that promotes viral attachment to the host cellular membrane by binding to its receptor ACE-2 via its Receptor-Binding Domain (RBD).
33161318 Angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and statins are known to improve endothelial dysfunction.
33164230 There are four identified factors that puts one at high-risk for infection and/or mortality creating a disparity: age, comorbidities, race/ethnicity, and gender. […] Data indicate that the older a person is, and/or the presence of obesity and diabetes, cardiovascular disease, and chronic kidney disease place one at higher risk for COVID-19. […] In the United States, specific race/ethnicities, particularly African Americans and Native Americans, are strong COVID-19 risk components. […] There is no evidence that racial/ethnic differences for COVID-19 are caused by ABO blood groups, use of angiotensin converting enzyme (ACE) inhibitors, or from amino acid substitutions in the SARS-CoV-2 spike protein. […] 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.
33168943 Concern has arisen about the role played in coronavirus disease 2019 (COVID-19) infection by angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs). […] This study was designed to assess the practice behaviors of physicians toward hypertension treatment with ACE-i or ARBs during the COVID-19 pandemic. […] A self-administered survey questionnaire consisting of 26 questions about current hypertension treatment with ACE-i/ ARBs was applied to cardiologists, internists, and family physicians in central and western Turkey, between 01 and 19 May 2020. […] Of the total respondents, 78.7% reported that they had not changed their antihypertensive medication prescribing pattern, 8.6% of clinicians had changed ACE-i/ ARBs medicine of patients during the COVID-19 pandemic and 12.7% of them were undecided. […] The median (±interquartile range) score indicating general reliance level of physicians in ACE-i/ARBs therapy was 8 ± 4 (range, 1-10). […] In multiple comparison analyses, the general reliance level in ACE-i/ARBs, reliance level when starting a new ACEi/ARBs and changing behavior in heart failure patients were significantly different with regard to the specialties (p:0.02, p:0.009, p:0.005 respectively). […] Although most of the physicians found the publications about ACE-i/ ARBs during the COVID-19 pandemic untrustworthy, there were variable levels of knowledge and reliance among different physicians and specialty groups. […] In general, the ACE-i/ ARBs prescribing habits were not affected by safety concerns during the COVID-19 pandemic in Turkey.
33170884 The SARS-CoV-2 virion responsible for the current world-wide pandemic COVID-19 has a characteristic Spike protein (S) on its surface that embellishes both a prefusion state and fusion state. […] The Up state is believed to allow binding of the virion to ACE-2 receptors on human epithelial cells, whereas the Down state is believed to be relatively inactive or reduced in its binding behavior.
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. […] The main feature of ACE inhibitory peptides is the location of the hydrophobic residue, usually Proline, at the C-terminus. […] Some already known bioactive peptides derived from marine resources have potential ACE inhibitory activity and can be considered therapeutic agents to treat hypertension. […] We also examined ACE2 modulation in sight of SARS2-Cov infection prevention.
33175403 SARS-CoV-2 binds the angiotensin-converting enzyme 2 (ACE-2) receptor; age-, racial-, and gender-specific differences in ACE-2 expression need to be elucidated in order to explain the differential clinical profiles between children and adults.
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.
33180562 SARS-CoV-2 infects host human cells by binding through the viral spike proteins to the angiotensin-converting enzyme 2 (ACE-2) receptor, fuses with the cell membrane, enters and starts its replication process in order to multiply its viral load.
33185828 In a short lapse of time, this virus was successful in spreading at a blistering pace throughout the globe, hence raising the flag of pandemic status. […] Possible strategies comprise viral vector-based, nucleic acid-based, protein-based, inactivated and weakened virus vaccines; COVID-19 vaccine being developed by deploying Hyleukin-7 technology; plant-based chimeric protein and subunit vaccines; humanized nano-bodies and human antibodies; intravenous immunoglobulin (IVIG) infusion therapy; inhibitors for ACE-2, Angiotensin 1 receptor (AT1R), complement system, viral proteins, host cell protease and endocytosis; shield immunity; IL-6R, NKG2A and hACE2-SARS-CoV-2-RBD interaction blocking monoclonal antibodies; SARS-CoV RdRp-based drugs, traditional Chinese medicine, repositioned and anti-viral drugs.
33186321 : Concerns over ACE inhibitor or ARB use to treat hypertension during COVID-19 remain unresolved. […] Thorough knowledge of these sources of bias and the appropriate methodologies to address them is crucial when evaluating observational studies to inform patient management decisions regarding whether ACE inhibitors or ARBs are associated with greater risk from COVID-19.
33186327 We also assessed the effect of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers on the outcome. […] In the subgroup of patients suffering from hypertension and/or heart failure (n = 1498), no differences were observed in the use of ACE inhibitors and angiotensin receptor blockers. […] No effects of ACE inhibitors and angiotensin receptor blockers on the outcome was reported.
33187703 Air pollution has been recently hypothesized to enhance the clinical severity of SARS-CoV-2 infection, acting through adverse effects on immunity, induction of respiratory and other chronic disease, upregulation of viral receptor ACE-2, and possible pathogen transportation as a virus carrier. […] We estimated ground-level nitrogen dioxide through its tropospheric levels using data available from the Sentinel-5P satellites of the European Space Agency Copernicus Earth Observation Programme before the lockdown.
33190109 It is postulated that either the cytokine storm induced by the viral infection or endothelial damage caused by viral binding to the ACE-2 receptor may activate a cascade leading to a hypercoaguable state.
33190150 In the face of the COVID-19 pandemic, the potential associations of SMA with the susceptibility to and prognostication of COVID-19 need to be clarified. […] Protein-protein interaction analysis by STRING suggested that loss-of-function of SMN1 might modulate COVID-19 pathogenesis through CFTR, CXCL8, TNF and ACE. […] Expression quantitative trait loci analysis also revealed a link between SMN1 and ACE2, despite low-confidence protein-protein interactions as suggested by STRING.
33194116 : ACE-i: Angiotensin converting enzyme inhibitor; ARB: Angiotensin receptor blocker; ARDS: Acute Respiratory Distress Syndrome; BiPAP: Bilevel positive airway pressure; CABG: Coronary artery bypass graft; CFR: Case fatality rate; COVID-19: Coronavirus disease 19; CPAP: Continuous positive airway pressure; CRP: C - Reactive Protein; CT: Computed tomography; DVT: Deep vein thrombosis; ECMO: Extra Corporeal Membrane Oxygenation; ESICM: European Society of Intensive Care Medicine; FiO2: Fraction of inspired O2; HFNC: High Flow Nasal Cannula; HITF: Hypoxia-Inducible Transcription Factor; IBM: International Business Machines; ICU: Intensive Care Unit; IL: Interleukin; IMV: Invasive Mechanical Ventilation; IQR: Interquartile Range; ISTH: International Society of Thrombosis Hemostasis; NIV: Non Invasive Ventilation; NY: New York; PAI: Plasminogen activator inhibitor; PaO2: partial pressure of arterial oxygen; PCV: Pressure Control Ventilation; PEEP: Positive End Expiratory Pressure; RGH: Rochester General Hospital; RRH: Rochester Regional Health; RT-PCR: Reverse transcriptase polymerase chain reaction; RSV: Respiratory Syncytial virus; SARS-CoV-2: Severe Acute Respiratory Syndrome Coronavirus 2; SD: Standard Deviation; STEMI: ST segment elevation myocardial infarction; TNF: Tumor necrosis factor; USA: USA; VTE: Venous thromboembolism.
33195397 Furthermore, we report ACE-2 genetic polymorphic variants affecting residues involved in close contacts with SARS-CoV-2 that might be associated to different infection risks.
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.
33195487 Here the virus can directly infect vascular tissues, via TMPRSS2 spike glycoprotein priming, thereby facilitating ACE-2-mediated viral entry. […] Activation of endothelial cells via the immune-mediated inflammatory response and viral infection of either endothelial cells or cells involved in endothelial homeostasis, are some of the multifaceted mechanisms potentially involved in the pathogenesis of vascular dysfunction within COVID-19 patients.
33197472 Angiotensin converting enzyme (ACE) genotypes are known to be associated with development of acute respiratory distress syndrome (ARDS) and resultant mortality. […] In the present study, we examined the association between distribution frequency of ACE genotypes and COVID-19 mortality. […] We undertook an ecological study to examine the association between ACE genotypes and COVID-19 mortality across 25 countries to represent different geographical regions of the world. […] The population frequencies of ACE genotypes were drawn from previously published reports and data on COVID-19-related mortality were extracted from ‘Worldometer’. […] Distribution frequency of ACE insertion/insertion (II) genotype may have a significant influence on COVID-19 mortality.
33199968 However, no vaccine has yet completed clinical trials and reached public domain.In spite of the challenges faced during previous vaccine trials, researchers have found that Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19 is structurally similar to the (SARS-CoV-1) and the Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV), which caused epidemics in 2003 and 2012 respectively. […] Both SARS strains show identical affinity towards the type-II alveolar pneumocytes angiotensin converting enzyme-2 (ACE-2) receptor binding domains and therefore, similar pathogenicity. […] The race to develop the vaccine is predominantly for individuals at high risk of developing the infection, i.e. population groups who are most susceptible to experiencing fatal symptoms of the coronavirus.
33200417 The renin-angiotensin system (RAS), also ACE 2 and TMPRSS2 play an important role in the cellular entry for SARS-CoV-2. […] Because the male genital system presents high ACE 2 expression, the importance of this pathway increases in COVID-19 cases.
33201172 The following variables were demonstrated to be associated with a worse prognosis: Radiologic Brixia score higher than 8, presence at baseline of hypertension, diabetes, chronic obstructive pulmonary disease, heart disease, cancer, previous treatment with ACE-inhibitors or anti-platelet drugs.
33202598 Severe acute respiratory syndrome - coronavirus 2 (SARS-CoV-2), the RNA Coronavirus responsible for the COVID-19 global pandemic, invades cells via the angiotensin converting enzyme 2 (ACE-2) receptor (ACE2R) that is appended in inflamed fat tissue and exacerbates the formation of the cytokines storm. […] White adipocytes express ACE-2 receptors in high concentration, especially in obese patients.
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. […] In parallel, clinical data from retrospective analysis of COVID-19 cohorts has revealed that ACE inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) may be beneficial in COVID-19. […] These findings have led to the initiation of clinical trials using approved drugs that target the generation (ACEIs) and actions (ARBs) of Ang II. […] However, treatment of COVID-19 with ACEIs/ARBs poses several challenges. […] 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).
33205916 Angiotensin-converting enzyme (ACE) 2 is a functional receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is up-regulated in patients with heart failure. […] No association was found between discontinuation of ACE-inhibitor or angiotensin-receptor blockers and COVID-19 test positivity.
33209159 The excess of morbidity and mortality due to diabetes was still not fully clarified; the role of demographic factors, the interaction of mediations with ACE-2 receptors and the role of co-morbidities will all need to be studied in order to identify the patient at risk profile, i.e. who can develop severe forms of the diseases and more outcomes.
33210357 COVID-19 is caused by the coronavirus SARS-CoV-2, which uses angiotensin-converting enzyme 2 (ACE-2) as a receptor for cellular entry. […] It is theorized that ACE inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) may increase vulnerability to SARS-CoV-2 by upregulating ACE-2 expression, but ACE-I/ARB discontinuation is associated with clinical deterioration. […] To determine whether ACE-I and ARB use is associated with acute kidney injury (AKI), macrovascular thrombosis and in-hospital mortality. […] We did not identify an association between ACE-I/ARB use and AKI, macrovascular thrombi or mortality. […] This supports the recommendations of the European and American Societies of Cardiology that ACE-Is and ARBs should not be discontinued during the COVID-19 pandemic.
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.
33211434 The race to elucidate the mechanisms of angiotensin, angiotensinogen and the angiotensin conversion enzyme cascade, by Braun Menéndez and Page teams, is a second chapter. […] The elucidation of RAAS pathophysiology naturally led to the synthesis of the antihypertensive captopril by Ondetti and Cushman, thereby opening the modern era of ACE inhibitors and ARII blockers. […] This new coronavirus uses the RAAS angiotensin conversion enzyme type 2 (ACE-2) as a gateway. […] The SARS-CoV-2/ACE-2 signalling pathway and its pathological effects on the cardio-respiratory and renal system of these patients initiate a new chapter. […] The interaction of SARS-Cov-2/ACE-2 axis with anti-hypertensive agents, as well as with ACE-2 activators and ACE-2 homologs, takes a part of an active international study searching for therapeutic targets.
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. […] The effect of ACE inhibitor (ACEI) treatment on the pneumonia incidence in non-COVID-19 patients (25 studies, 330 780 patients) was associated with a 26% reduction of pneumonia risk (odds ratio [OR]: 0.74, P < .001). […] Pneumonia-related death cases in ACEI-treated non-COVID-19 patients were reduced by 27% (OR: 0.73, P = .004). […] Results from 11 studies (8.4 million patients) showed that the risk of getting infected with the SARS-CoV-2 virus was reduced by 13% (OR: 0.87, P = .014) in patients treated with ACEI, whereas analysis from 10 studies (8.4 million patients) treated with ARBs showed no effect (OR, 0.92, P = .354). […] ACEIs reduce the risk of getting infected with the SARS-CoV-2 virus. […] ACEIs also reduce the risk of non-COVID pneumonia. […] All-cause mortality due to non-COVID pneumonia is reduced by ACEI and potentially by ARBs.
33219294 The association between angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin II receptor blocker (ARB) and the risk of mortality in hospitalized patients with severe coronavirus disease 2019 (COVID-19) was investigated. […] Patients were classified based on whether they received ACE-I or ARB before COVID-19 diagnosis. […] Of 130 patients with COVID-19, 30 (23.1%) who received ACE-I or ARB exhibited an increased risk of in-hospital mortality (adjusted hazard ratio, 2.20; 95% confidence interval [CI], 1.10-4.38; P = 0.025). […] ACE-I or ARB was also associated with severe complications, such as acute respiratory distress syndrome (ARDS) (adjusted odds ratio [aOR], 2.58; 95% CI, 1.02-6.51; P = 0.045) and acute kidney injury (AKI) (aOR, 3.06; 95% CI, 1.15-8.15; P = 0.026). […] Among the patients with ACE-I or ARB therapy, 8 patients (26.7%) used high equivalent doses of ACE-I or ARB and they had higher in-hospital mortality and an increased risk of ARDS and AKI (all, P < 0.05). […] ACE-I or ARB therapy in patients with severe COVID-19 was associated with the occurrence of severe complications and increased in-hospital mortality. […] The potentially harmful effect of ACE-I or ARB therapy may be higher in patients who received high doses.
33222915 During their protracted hospitalizations, subsequent imaging disclosed intracranial hemorrhages, including intracerebral and subarachnoid hemorrhages, in the context of anticoagulation and coagulopathy. […] We believe this is related to the tropism of SARS-CoV-2 to the endothelial lining of the cerebral vasculature via their angiotensin-converting enzyme (ACE) II receptors. […] Given our findings, we advocate heightened vigilance for intracerebral hemorrhage events, and scanning when practicable, in COVID-19 patients which have prolonged ventilatory support and depressed neurologic examinations.
33224380 Angiotensin-converting enzyme (ACE) 2 is the cellular entry receptor of SARS-CoV-2. […] 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.
33224575 The main activation of the signal pathways for the production of inflammatory cytokines are the toll-like receptors that recognize the presence of viral nucleic acids and the ACE-2 receptors, that the virus uses to infect the cells. […] The binding to ACE-2 also allows to promote high levels of angiotensin II by promoting high levels of blood pressure.
33224599 The mechanism by which COVID-infected patients develop cardiac complications remains unclear, though it may be mediated by increased ACE-2 gene expression. […] Despite initial concerns, there is no evidence that angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy increases risk for myocardial injury among those infected with COVID-19.
33227287 The virus utilizes spike proteins present on its surface to recognize ACE-2 receptors present on the host cells to enter the cell cytoplasm and replicate.
33227636 In a recent series of articles, Manning and Fink [1-3] use national-level data to describe associations between case-fatality ratios and male and female finger ratios (2D:4D), a suggested measure of prenatal androgen exposure, as well as angiotensin-converting enzyme (ACE) allele and genotype frequencies. […] The authors suggest that 2D:4D is linked with ACE variant prevalence, and that higher male 2D:4D is associated with higher case fatality ratios, and point to 2D:4D as a useful prognostic measure for COVID-19 susceptibility. […] 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). […] However, intense research is going on to screen and ace the ‘magic bullets’ for the management of SARS-CoV2 infection worldwide.
33231487 Speculations whether treatment with angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin II receptor blockers (ARB) predisposes to severe coronavirus disease 2019 (COVID-19) or worsens its outcomes. […] This study assessed the association of ACE-I/ARB therapy with the development of severe COVID-19. […] ACE-I/ARB therapy associations with severe COVID-19 on the day of hospitalization, intensive care unit (ICU) admission, mechanical ventilation and in-hospital death on follow-up were tested using a multivariate logistic regression model adjusted for age, obesity, and chronic illnesses. […] = .87) versus not using ACE-I/ARB. […] Patients with hypertension or cardiovascular diseases receiving ACE-I/ARB therapy are not at increased risk for severe COVID-19 on admission to the hospital. […] ICU admission, mechanical ventilation, and mortality are not associated with ACE-I/ARB therapy. […] Maintaining ACE-I/ARB therapy during hospitalization for COVID-19 lowers the likelihood of death.
33232272 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily interacts with the cell surface receptor angiotensin-converting enzyme (ACE) 2 and other accessory proteins such as 78 kDa glucose-regulated protein 78 (GRP78) and CD147.
33232783 The mode of entry of SARS-CoV-2 is via the angiotensin converting enzyme 2 (ACE-2) receptors present on the epithelial lining of lungs, gastrointestinal tract, and mucus membranes.
33233425 The aim of the study was to characterize the interaction between SARS-CoV-2 and Angiotensin-Converting Enzyme 2 (ACE2) functional networks with a focus on CVD. […] Using the network medicine approach and publicly available datasets, we investigated ACE2 tissue expression and described ACE2 interaction networks that could be affected by SARS-CoV-2 infection in the heart, lungs and nervous system. […] We compared them with changes in ACE-2 networks following SARS-CoV-2 infection by analyzing public data of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). […] We also performed miRNA-target predictions to identify which miRNAs regulate ACE2-related networks and could play a role in the COVID19 outcome. […] We found similar ACE2 expression confidence levels in respiratory and cardiovascular systems, supporting that heart tissue is a potential target of SARS-CoV-2. […] Analysis of ACE2 interaction networks in infected hiPSC-CMs identified multiple hub genes with corrupted signaling which can be responsible for cardiovascular symptoms. […] Enrichment analysis revealed multiple diseases associated with the interaction networks of ACE2, especially cancerous diseases, obesity, hypertensive disease, Alzheimer’s disease, non-insulin-dependent diabetes mellitus, and congestive heart failure. […] Among affected ACE2-network components connected with the SARS-Cov-2 interactome, we identified AGT (Angiotensinogen), CAT (Catalase), DPP4 (Dipeptidyl Peptidase 4), CCL2 (C-C Motif Chemokine Ligand 2), TFRC (Transferrin Receptor) and CAV1 (Caveolin-1), associated with cardiovascular risk factors. […] We described for the first time miRNAs which were common regulators of ACE2 networks and virus-related proteins in all analyzed datasets. […] The top miRNAs regulating ACE2 networks were miR-27a-3p, miR-26b-5p, miR-10b-5p, miR-302c-5p, hsa-miR-587, hsa-miR-1305, hsa-miR-200b-3p, hsa-miR-124-3p, and hsa-miR-16-5p. […] Our study provides a complete mechanistic framework for investigating the ACE2 network which was validated by expression data.
33234760 The patient was treated symptomatically with fluid replacement, optimization of electrolyte balance and oxygen supplementation. […] COVID-19 pathogenesis is believed to be mediated by the angiotensin converting enzyme 2 (ACE-2) receptor over the cell surface. […] ACE-2, which acts as a receptor for viral entry into host cells are highly expressed in pancreatic cells.
33237815 The availability of angiotensin-converting enzyme 2 (ACE2) receptors may reportedly increase the susceptibility and/or disease progression of COVID-19. […] In this paper, we hereby review the evidence pertaining to ACE2’s relationship to common comorbidities, risk factors, and therapies associated with severe and critical COVID-19. […] The tertiary factors of ACE inhibitors and angiotensin II receptor blockers had limited-to-moderate evidence.
33238910 To explore the clinical significance of serum angiotensin-converting enzyme (ACE) activity in coronavirus disease 2019 (COVID-19). […] The serum ACE activity was measured at baseline and during the recovery phase, and its relationship with clinical condition was analyzed. […] In comparison to those of normal controls, the baseline serum ACE activities of subjects in the severe group and nonsevere group were decreased, with the lowest level in the severe group. […] However, the serum ACE activity increased in the recovery phase, and there were no significant differences among the severe group, nonsevere group and normal control group. […] Serum ACE activity could be used as a marker to reflect the clinical condition of COVID-19 since low activity was associated with the severity of COVID-19 at baseline, and the activity increased with the remission of the disease.
33244671 Experimental studies suggest both coronaviruses and influenza viruses engage with the angiotensin-converting enzyme 2 (ACE 2) and tetraspanin antibodies, and that ACE 2 tetraspanin antibodies in turn may inhibit both coronavirus and low-pathogenicity influenza A viruses (LP IAV) infections.
33246009 ACE 2 mRNA levels were quantified in fat depots of a separate group of non-COVID-19 subjects using RT-qPCR. […] On the basis of an exploratory analysis ACE 2 in the visceral fat may be a trigger for the cytokine storm, and this needs to be clarified by future studies.
33251800 Oral administration of IRW to spontaneously hypertensive rats (SHRs) can significantly reduce blood pressure, via upregulation of ACE2, but not through the inhibition of ACE. […] ACE2 converts Ang II into Ang (1-7), thus lowering blood pressure via Mas receptor (MasR); coinfusion of Mas receptor antagonist A779 and IRW in SHRs abolished blood pressure-lowering effect of IRW, supporting a key role of ACE2/Ang (1-7)/MasR axis.
33254494 SARS-CoV-2 interaction with the ACE-2 receptor cannot alone explain the demography and remarkable variation in clinical progression of Covid-19 infection.
33254506 The angiotensin converting enzyme-2 (ACE-2), a component in the renin-angiotensin-aldosterone system (RAAS), plays as cell surface receptors for SARS-CoV-2. […] Thus, the combination of DPP4 inhibition and suppression of ACE-2/RAAS may be a novel therapeutic strategy for combating this pandemic.
33254514 These medications are readily available and testing this theory involves determination of the correct dosage of angiotensin receptor blockers or ACE inhibitors (via dilution in water) that can be used as nasal lavage and performing efficacy trials.
33254553 Angiotensin-converting enzyme 2 (ACE2) is the receptor responsible for SARS-CoV-2 access to human cells, and ACE2 expression is increased in patients with diabetes and hypertension treated with ACE-inhibitors or angiotensin II receptor blockers. […] We hypothesize that an upregulation of ACE2 due to its non-enzymatic glycation could be considered, as well as a change of the protein tertiary structure in terms of amino acid (mostly lysine) available to be glycated. […] In fact, in a single ACE2 molecule, 34 lysine residues are present in the extracellular portion, and at least one of these is co-involved in a fundamental hydrogen-bond interaction with the SARS-CoV-2 receptor binding domain (RBD). […] The worse outcome of COVID-19 in people with diabetes could be related to the non-enzymatic glycation that triggers the activity of ACE2.
33254589 SARS-CoV-2 utilizes Angiotensin-Converting Enzyme II (ACE2) for entry in the host cell, and Transmembrane Protease, Serine 2 (TMPRSS2) to prime spike protein of SARS-CoV-2. […] Testosterone induces ACE-2 expression, a critical pulmonary protective enzyme.
33254590 The angiotensin-converting enzyme 2(ACE-2) receptors with approx. […] 0.8% congestion in conjunctival surface, leads to increase susceptibility of Covid-19 transmission through ocular surface. […] It has been observed that prophylactic measures such as goggle or face shield are unable to offer complete protection against ocular transmission of SRS-CoV-2. […] Hence, it is hypothesized that topical ocular prophylaxis using biocompatible polymers with reported in-vitro and in-vivo evidence of ACE inhibition and antiviral activity appears to be a promising strategy for preventing ocular transmission of Covid-19 to healthcare workers. […] They are capable of binding to ACE-2 receptors which may provide highly potential trails to block virus entry to host cells. […] This article discusses the description of structural and functional attributes of ACE-2 to identify appropriate polymer with better binding affinity.
33262955 Making entry into host the cell through already established ACE-2 receptor concerted with the action of TMPRSS2, is considered important for the virus.
33263566 Androgens play a fundamental role in the morbidity and mortality of COVID-19, inducing both the ACE-2 receptor to which SARS-CoV-2 binds to gain entry into the cell, and TMPRS22, the transmembrane protease that primes the viral spike protein for efficient infection. […] During the current pandemic, the unrestricted availability of oral DHEA as a “dietary supplement” cannot be considered safe without proof from placebo-controlled clinical trials that it is not contributing to the severity of COVID-19.
33264497 Angiotensin-converting enzyme 2 (ACE-2) protein on the epithelial surface is the primary entry receptor for SARS-CoV-2, and protein-protein interaction assays demonstrate high-affinity binding of the spike protein (S protein) to ACE-2. […] Tight binding to ACE-2 by a conserved viral RBD suggests the ACE2-RBD interaction is likely optimal.
33274196 Angiotensin-converting enzyme 2 (ACE2) is the outer surface protein of the cell membrane that is abundantly distributed in the heart, lungs, and kidneys and plays an important role in molecular docking of the severe acute respiratory syndrome coronavirus 2. […] In this study, we aimed to analyze the difference in the survival rate according to ACE2 expressions in pan-cancer. […] Only ccRCC had statistical significance, and high ACE2 expression is related to good prognosis. […] It is known that the ACE inhibitor, a primary antihypertensive agent, increases ACE2 expression. […] Based on these results, we believe that the ACE inhibitor will be important to increase the lifespan of ccRCC patients.
33277453 We investigated the adverse effect of ACEIs in diabetic and nondiabetic patients with COVID-19. […] Cox regression analysis revealed that age (adjusted hazard ratio [HR] = 1.04, 95% CI: 1.03 to 1.06), diabetes mellitus (adjusted HR = 2.07, 95% CI: 1.32 to 3.26), immunocompromised patients (adjusted HR = 2.33, 95% CI: 1.29 to 4.21), acute kidney injury (AKI) (adjusted HR = 3.23, 95% CI: 2.01 to 5.19), ICU admission (adjusted HR = 2.48, 95% CI: 1.46 to 4.21), Asthma and COPD (adjusted HR = 2.13, CI:1.6 to 4.28) and ACEI (adjusted HR = 3.08, 95% CI: 1.56 to 6.06), respectively were associated with in-hospital death. […] Among diabetic patients, ACEI (adjusted HR = 3.51, 95% CI: 1.59 to 7.75), AKI (adjusted HR = 3.32, 95% CI: 1.76 to 6.45) and ICU admission (adjusted HR = 3.64, 95% CI: 1.530 to 8.65) were associated with increased mortality. […] The Kaplan-Meier survival curve showed a lower survival rate in diabetic patients with ACE inhibitor (adjusted HR = 3.36, 95% CI: 2.25 to 7.71). […] ACEIs may harm the diabetic patient’s outcome with COVID-19. […] Further studies can confirm if ACE inhibitors have an adverse effect on COVID-19 diabetic patient’s mortality.
33278189 SARS-CoV-2 requires angiotensin converting enzyme (ACE)2 as a receptor for cell entry and infection. […] While both ACE inhibitors and spironolactone can upregulate tissue ACE2, there are important points of discrimination between these approaches. […] The virus requires proteolytic processing of its spike protein by transmembrane protease receptor serine type 2 (TMPRSS2) to enable binding to cellular ACE2.
33280062 Angiotensin-converting enzyme (ACE) 2 is known to be a functional receptor for SARS-CoV-2 in the current pandemic. […] Soluble ACE2 (sACE2) concentrations are elevated in patients with various cardiovascular disorders including heart failure. assay by Cloud-Clone Corporation and associated with clinical, laboratory and echocardiographic parameters. […] Median sACE2 levels were increased in patients with complex CHD as compared to healthy controls (761.9 pg/ml vs 365.2 pg/ml, p < 0.001). […] Moreover, sACE2 concentrations were significantly elevated in patients with a higher NYHA class ≥ III (1856.2 pg/ml vs 714.5 pg/ml in patients with NYHA class I/II, p < 0.001). […] Using linear regression analysis, higher sACE2 levels were associated with a higher NYHA class ≥ III, more severe CHD, a morphological left systemic ventricle, higher creatinine and the use of mineralocorticoid receptor antagonists (MRA) in the univariable model. […] The use of ACE inhibitors or angiotensin receptor blockers (ARB) was associated with lower sACE2 levels. […] In the multivariable model, higher sACE2 levels were independently associated with a higher NYHA class ≥ III (p = 0.002) and lower sACE2 levels with the use of ACE inhibitors or ARB (p = 0.001). […] Soluble ACE2 concentrations were significantly increased in all types of complex CHD with highest levels found in patients with NYHA class ≥ III. […] Moreover, a higher NYHA class ≥ III was the most significant determinant that was independently associated with elevated sACE2 concentrations.
33281941 While data profiling the gut microbiome in COVID-19 infection to date are limited, they support the possibility of several routes of interaction between COVID-19, the gut microbiome, angiotensin converting enzyme 2 (ACE-2) expression in the small bowel and colon and gut inflammation. […] A protein called ACE-2, which is found in the small intestine among other sites, is a key receptor for COVID-19 virus entry; there is evidence that the gut microbiome influences ACE-2 receptor expression, and hence may play a role in influencing COVID-19 infectivity and disease severity.
33284956 Twenty years ago, the discovery of angiotensin-converting enzyme 2 (ACE2) was an important breakthrough dramatically enhancing our understanding of the renin-angiotensin system (RAS). […] The classical RAS is driven by its key enzyme ACE and is pivotal in the regulation of blood pressure and fluid homeostasis. […] More recently, it has been recognised that the protective RAS regulated by ACE2 counterbalances many of the deleterious effects of the classical RAS. […] Liver-specific overexpression of ACE2 in mice with liver fibrosis has proved to be highly effective in antagonising liver injury and fibrosis progression. […] Importantly, despite its highly protective role in disease pathogenesis, ACE2 is hijacked by SARS-CoV-2 as a cellular receptor to gain entry to alveolar epithelial cells, causing COVID-19, a severe respiratory disease in humans. […] As an unprecedented number of COVID-19 patients have been affected globally, there is an urgent need to discover novel therapeutics targeting the interaction between the SARS-CoV-2 spike protein and ACE2. […] Understanding the role of ACE2 in physiology, pathobiology and as a cellular receptor for SARS-CoV-2 infection provides insight into potential new therapeutic strategies aiming to prevent SARS-CoV-2 infection related tissue injury. […] This review outlines the role of the RAS with a strong focus on ACE2-driven protective RAS in liver disease and provides therapeutic approaches to develop strategies to prevent SARS-CoV-2 infection in humans.
33293279 To examine the impact of ACE inhibitor (ACE-I)/angiotensin receptor blocker (ARB) use on rate of SARS-CoV-2 infection and adverse outcomes. […] We estimated confounder-adjusted ORs for a positive test among all SARS-CoV-2 tested, and inverse probability of treatment weighted 30-day risk and risk ratios (RRs) of hospitalisation, intensive care unit (ICU) admission and mortality comparing current ACE-I/ARB use with calcium channel blocker (CCB) use and with non-use. […] Users of ACE-I/ARB had a marginally increased rate of a positive PCR when compared with CCB users (aOR 1.17, 95% CI 1.00 to 1.37), but not when compared with non-users (aOR 1.00 95% CI 0.92 to 1.09). […] Among PCR-positive individuals, 1466 (11%) were ACE-I/ARB users. […] The weighted risk of hospitalisation was 36.5% in ACE-I/ARB users and 43.3% in CCB users (RR 0.84, 95% CI 0.70 to 1.02). […] The risk of ICU admission was 6.3% in ACE-I/ARB users and 5.4% in CCB users (RR 1.17, 95% CI 0.64 to 2.16), while the 30-day mortality was 12.3% in ACE-I/ARB users and 13.9% in CCB users (RR 0.89, 95% CI 0.61 to 1.30). […] The associations were similar when ACE-I/ARB users were compared with non-users. […] ACE-I/ARB use was associated neither with a consistently increased rate nor with adverse outcomes of SARS-CoV-2 infection. […] Our findings support the current recommendation of continuing use of ACE-Is/ARBs during the SARS-CoV-2 pandemic.
33300456 Approx. 50% of studies exclusively targeted 3CLpro of SARS-CoV-2, and only two studies targeted ACE/TMPSS2 for inhibiting host viral interactions.
33303459 Smoking (HR 0.62; 95% CI 0.41 to 0.93; p=0.022), ACE inhibitors (HR 0.68; 95% CI 0.47 to 0.99; p=0.046) and antihistamine (HR 0.47; 95% CI 0.22 to 1.01; p=0.052) were associated with a lower risk. […] Receiving ACE inhibitors (HR 0.66; 95% CI 0.44 to 0.99; p=0.046) and influenza vaccination (HR 0.63; 95% CI 0.44 to 0.91; p=0.012) was associated with decreased risk. […] Conversely, receiving ACE inhibitors, antihistamine and influenza vaccination could be protective, which should be closely investigated in further studies specifically focused on these concerns.
33305304 Herein, combination molecular docking with dissipative particle dynamics (DPD) simulations is used to theoretically design angiotensin-converting enzyme inhibitor (ACEI)-containing remdesivir-loaded PLGA nanoparticles (NPs) for anti-SARS-CoV-2 therapy. […] Based on the therapeutic and lung protective effect of ACEI, the classical lisinopril molecule covalently grafted onto PLGA (L-PLGA) has been used to encapsulate remdesivir. […] A binding model is used to confirm the interactions between lisinopril and ACE on the surface of cells, as well as remdesivir and its intracellular targeting protein (RNA-dependent RNA polymerase (RdRp)). […] The lisinopril molecules were directly demonstrated to be on the surface of L-PLGA NPs.
33306581 Objectives/Introduction: Novel coronavirus 2019 (COVID-19) binds angiotensin-converting enzyme-2 (ACE-2) receptors to enter the cell. […] Helicobacter pylori is known to increase the expression of ACE-2 receptors in the gastrointestinal tract.
33309398 COVID-19 is a disease with many clinical, biochemical, and radiological signs that has a predilection for the lungs, probably because of the high number of ACE-2 receptors in this organ.
33310740 It has been speculated that renin angiotensin system (RAS) blockers may promote COVID-19 by increasing ACE2, which SARS-CoV-2 uses to enter host cells, along with the host protease TMPRSS2. […] Taking a reverse translational approach and by combining in situ hybridization, primary cell isolation, immunoblotting, qRT-PCR and LC-MS/MS we studied lung and kidney ACE2 and TMPRSS2 in diabetic mice mimicking host factors linked to severe COVID-19. […] In healthy young mice, neither the ACE inhibitor ramipril nor the AT1 receptor blocker telmisartan affected lung or kidney ACE2 or TMPRSS2, except for a small increase in kidney ACE2 protein with ramipril. […] In contrast, mice with comorbid diabetes (aging, high fat diet and streptozotocin-induced diabetes) had heightened lung ACE2 and TMPRSS2 protein levels and increased lung ACE2 activity. […] ACE2 was similarly upregulated in the kidneys of mice with comorbid diabetes compared to aged controls, whereas TMPRSS2 (primarily distal nephron) was highest in telmisartan-treated animals. […] Upregulation of lung ACE2 activity in comorbid diabetes may contribute to increased risk of severe COVID-19.
33312199 In addition, the role of the main biological processes that may connect metabolic alterations to SARS-CoV-2 infection such as hyperglycemia, immune system deregulation, ACE-2 receptor modulation, and inflammatory response is described.
33334050 The pathogenic mechanisms of SARS-CoV-2 infection are mediated by the binding of SARS-CoV-2 spikes to the human angiotensin-converting enzyme 2 (ACE-2) receptor. […] The overexpression of human ACE-2 is associated with the disease severity in SARS-CoV-2 infection, demonstrating that viral entry into cells is a pivotal step. […] In addition, kidney dysfunction could exacerbate the inflammatory response started in the lungs and might cause further renal impairment and multi-organ failure.
33336781 PubMed search was performed focusing on the role of ACE 2 receptors in allowing the viral entry into cells, the role of ACE 2 downregulation in triggering the tissue pathology or in accelerating previous disease states, the role of increased levels of Angiotensin II in determining endothelial dysfunction and the enhanced vascular permeability, the role of the dysregulation of the renin angiotensin system in COVID-19 and the role of cytokine storm. […] Even if ACE2 is the main receptor of SARS-CoV-2 and the main entry point into cells for the virus, ACE2 expression does not always explain the observed marked inter-individual variability in clinical presentation and outcome, evidencing the complexity of this disorder.
33336824 ACE and vasoconstrictive AT1R clustered with the prorenin receptor. […] ACE2 and dilatory MAS1 clustered with nine RAS-related genes, highly expressed in: Liver; Cardiac_Myocytes; Skeletal_Muscle; Uterus; Kidney; Lung; Small_Intestine; Smooth_Muscle. […] Reduced vasodilation by ACE2 lead to vasoconstriction and suboptimal tissue perfusion patterns.
33337478 Event/patient numbers were extracted, comparing ACE inhibitor/ARB treatment (and each separately), to treatment with neither drug, for the outcomes: (a) Likelihood of SARS-CoV-2 infection; (b) CoViD-19 severity (including hospitalisation, Intensive Therapy Unit (ITU), ventilation); (c) Case-fatality. […] In patients with hypertension, ACE inhibitor or ARB treatment was not associated with a greater likelihood of SARS-CoV-2 infection in 60,141 patients (OR 1.06, 95% CI 0.99-1.14), hospitalisation in 5,925 patients (OR 0.90, 0.62-1.31), ITU in 7,218 patients (OR 1.06, 0.73-1.56), ventilation (or ITU/ventilation/death) in 13,163 patients (OR 0.91, 0.72-1.15) or case-fatality in 18,735 patients with 2,893 deaths (OR 0.75, 0.61-0.92). […] ACE inhibitors and ARBs appear safe in the context of SARS-CoV-2 infection and should not be discontinued.
33338639 The reported association between an insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene and the risk for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) remains controversial despite the publication of four meta-analyses on this topic. […] Significant associations of the ACE I/D polymorphism with the risk of ALI/ARDS were indicated in Caucasians and children as well as in Asians in mortality analysis. […] ACE genotypes may be useful for ALI/ARDS therapy for patients with COVID-19.
33338751 Furthermore, it regulates the expression of Hippo, MAPK, GSK-3β, PI3K/AKT/mTOR, STAT3, TLR, IκB/NF-κB, Nrf2/HO-1, ACE, eNOS / NO, AChE and BrdU/NeuN.
33341613 Co-occurrence of SARS-CoV-2 infection and wildfire smoke inhalation may present an increased risk for COVID-19 illness in wildland firefighters due to PM based transport of SARS CoV-2 virus and up-regulation of angiotensin-converting enzyme II (ACE-2) (i.e. […] ACE-2 functions as a trans-membrane receptor, allowing the SARS-CoV-2 virus to gain entry into the epithelial cell). […] Current infection control measures, including social distancing, wearing cloth masks, frequent cleaning and disinfecting of surfaces, frequent hand washing, and daily screening for COVID-19 symptoms are very important measures to reduce infections and severe health outcomes.
33341894 COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which binds to angiotensin-converting enzyme 2 (ACE2) on the cell surface and downregulates ACE2, likely elevating the ratio of angiotensin-converting enzyme (ACE) to ACE2. […] The overreaction of the immune system, combined with the cytokine storm and ACE dominance, is purported to cause the condition of COVID-19 patients to deteriorate rapidly. […] Dietary seaweeds contain numerous components, including ACE inhibitory peptides, soluble dietary fibers (eg, fucoidan, porphyran), omega-3 fatty acids, fucoxanthin, fucosterol, vitamins D3 and B12, and phlorotannins. […] It is possible that ACE inhibitory components could minimize the ACE dominance caused by SARS-CoV-2 infection.
33342421 It is the angiotensin-converting enzyme-2 (ACE-2) to which the COVID-19 virus binds and upon downregulation of which the pulmonary permeability increases and results in the filling of alveoli by proteinaceous fluids, which finally results in ARDS. […] ARDS can be assisted by angiotensinII type-1 receptor (AT-1R) blocker and ACE-2 upregulator. […] ACE-2 upregulation will ensure less formation of angiotensin II, vasodilatory effects due to the formation of angiotensin (1-7), increased breakdown of bradykinin at lung level. […] It acts across the board and acts as both an AT-1R blocker, ACE-2 upregulator.
33347477 Because ACE-2 may be modulated by angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), there is concern that patients treated with ACEIs and ARBs are at higher risk of coronavirus disease 2019 (COVID-19) pneumonia. […] This study sought to analyze the association of COVID-19 pneumonia with previous treatment with ACEIs and ARBs. […] No difference was found for treatment with ACEIs (12.7% vs. […] Significant interaction between ARBs and ACEIs for the risk of COVID-19 was observed in patients aged > 60 years, women, and hypertensive patients. […] This study suggests that ACEIs and ARBs are not similarly associated with COVID-19.
33349849 There has been uncertainty about the safety or benefit of angiotensin-converting enzyme (ACE) inhibitors during the Covid-19 pandemic. […] We used Mendelian randomization using genetic determinants of serum-ACE levels to test whether decreased ACE levels increase susceptibility to SARS-CoV-2 infection or Covid-19 severity, while reducing potential bias from confounding and reverse causation in observational studies. […] Genetic variants strongly associated with ACE levels, which were nearby the ACE gene, were identified from the ORIGIN trial and a separate genome-wide association study (GWAS) of ACE levels from the AGES cohort. […] Genetic variants were identified that explain between 18% and 37% of variance in ACE levels. […] Using genetic variants from the ORIGIN trial, a standard-deviation decrease in ACE levels was not associated with an increase in Covid-19 susceptibility [odds ratio (OR): 1.02, 95% confidence interval (CI): 0.90, 1.15], hospitalization (OR: 0.86, 95% CI: 0.68, 1.08) or severe disease (OR: 0.74, 95% CI: 0.51, 1.06). […] Genetically decreased serum ACE levels were not associated with susceptibility to, or severity of, Covid-19 disease. […] These data suggest that individuals taking ACE inhibitors should not discontinue therapy during the Covid-19 pandemic.
33351311 To assess the effect of clinical and demographic parameters (age, gender, body mass index (BMI), glycemic control (HbA1c), and antidiabetic and antihypertensive drugs, including ACE inhibitors and ARBs) on clinical outcomes (recovery or death) in patients with type 2 DM. […] The degree of lethality was found to be significantly higher in males (OR=2.08; 95% CI 1.1–3.9; p=0.022) and in patients on insulin therapy (OR=2.67; 95% CI; 1.42–5.02; p=0.002), while it was significantly lower in patients with an age <65 years (OR=0.34; 95% CI 0.18–0.67; p=0.001) and in patients receiving metformin (OR=0.26; 95% CI 0.14–0,5; p<0.0001), antihypertensive therapy (OR=0.43; 95% CI 0.22–0.82; p=0.009), β-blockers (OR=0.26; 95% CI 0.08–0.86; p=0.018), diuretics (OR=0.4; 95% CI 0.17–0.93; p=0.028) and renin-angiotensin system blockers (ACE inhibitors or ARBs) (OR=0.36; 95% CI 0.18–0.74; p=0.004). […] 6.8 years, respectively; p<0.0001), worse overall glyacemic control (HbA1c: 8.1% vs. 
33356523 In fact, angiotensin-converting enzyme 2 (ACE-2), the main site of entry of SARS-CoV-2 into the cell, was found to be present in the ductal elements of salivary gland and several other tissues.
33363465 Literature experimental results identified angiotensin-converting enzyme ACE and Spike proteins particularly involved in COVID-19. […] Our bioinformatics analysis predicted microRNAs (miRs), miR-335-5p and miR-26b-5p, as being modulated by Spike and ACE together with histone deacetylate (HDAC) pathway. […] Notably, our results identified ACE/ACE2-ATR1-Cholesterol-HDAC axis signals that also matched with some available clinical data.
33378062 Recently, two influential articles that reported the association of (hydroxy)chloroquine or angiotensin converting enzyme (ACE) inhibitors and coronavirus disease 2019 (COVID-19) mortality were retracted due to significant methodological issues. […] In addition, our study demonstrated that use of ACE inhibitors or angiotensin receptor blockers (ARBs) was associated with reduced risk of mortality (0.77; 0.65-0.91). […] When analyzing the same clinical issues with the two retracted papers through a systematic review of randomized controlled trials and relevant cohort studies, we found out that (hydroxy)chloroquine monotherapy was not associated with higher risk of mortality, and that the use of ACE inhibitors or ARBs was associated with reduced risk of mortality in COVID-19 patients.
33380345 Since angiotensin-converting enzyme (ACE)-2 is a receptor for SARS-CoV-2, and ACE inhibitors and angiotensin receptor blockers are predicted to increase ACE-2 expression, it was initially feared that their use might exacerbate COVID-19. […] This is perhaps because SARS-CoV-2 entry may deplete ACE-2, tipping the balance towards angiotensin II-ACE-1-mediated classical RAS activation: exacerbating hypoperfusion and promoting inflammation. […] It may be relevant that APOE ε4 individuals, who seem to be at increased risk of COVID-19, also have lowest ACE-2 activity.
33382930 Insight is provided into the effect of vitamin A on ACE-2 expression in the respiratory tract and its association with the prognosis of Covid-19 patients.
33389262 Angiotensin-converting enzyme 2 (ACE2) is not only an enzyme but also a functional receptor on cell surfaces through which SARS-CoV-2 enters the host cells and is highly expressed in the heart, kidneys, and lungs and shed into the plasma. […] ACE2 is a key regulator of the renin-angiotensin-aldosterone system (RAAS). […] SARS-CoV-2 causes ACE/ACE2 balance disruption and RAAS activation, which leads ultimately to COVID-19 progression, especially in patients with comorbidities, such as hypertension, diabetes mellitus, and cardiovascular disease. […] Therefore, ACE2 expression may have paradoxical effects, aiding SARS-CoV-2 pathogenicity, yet conversely limiting viral infection. […] This article reviews the existing literature and knowledge of ACE2 in COVID-19 setting and focuses on its pathophysiologic involvement in disease progression, clinical outcomes, and therapeutic potential.
33390179 With respect to SARS-CoV-2, an intronic Alu within the ACE gene is hypothesized to be associated with COVID-19 susceptibility and morbidity.
33390724 COVID-19 mechanisms in the nerve and musculoskeletal damage are believed to be caused by the expression and distribution of angiotensin-converting enzyme 2 (ACE-2).
33391924 They do so primarily by binding to the membrane-bound form of angiotensin-converting enzyme 2 (ACE-2) receptors. […] However, since these receptors are also expressed in the heart and blood vessels, coronavirus can also cause damage to these organs by binding to the ACE-2 receptors.
33394058 The cardiovascular system plays a causal role in this context, as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) invades host cells via the angiotensin-converting enzyme 2 (ACE-2), an enzyme in the renin-angiotensin system.
33395036 We provide a comprehensive overview of angiotensin-converting enzyme 2 (ACE2) as a possible candidate for pharmacological approaches to halt inflammatory processes in different pathogenic conditions. […] ACE2 has quickly gained prominence in basic research as it has been identified as the main entry receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). […] ACE2 acts as an endogenous counter-regulator to the pro-inflammatory and pro-fibrotic pathways triggered by ACE through the conversion of Ang II into the vasodilatory peptide Ang 1-7. […] We discuss the structure, function and expression of ACE2 in different tissues. […] We also briefly describe the role of ACE2 as a pivotal driver across a wide spectrum of pathogenic conditions, such as cardiac and renal diseases. […] Furthermore, we provide the most recent data concerning the possible role of ACE2 in mediating SARS-CoV-2 infection and dictating COVID-19 severity.
33395080 A controversial issue relates to the safety of drugs blocking the renin–angiotensin system as an angiotensin-converting enzyme (ACE) homologue, ACE2, serves as the receptor for viral entry into host cells.
33395782 Past lessons and new data teach us that severe acute respiratory syndrome coronaviruses (SARS-CoV and SARS-CoV-2) can enter islet cells via angiotensin converting enzyme-2 (ACE-2) receptors and cause reversible β-cell damage and transient hyperglycemia.
33396184 Angiotensin-converting enzyme II (ACE2) is the functional receptor for SARS-CoV-2 entry into host cells. […] ACE2 exists as a membrane-bound protein on major viral target pulmonary epithelial cells, and its peptidase domain (PD) interacts SARS-CoV-2 spike protein with higher affinity. […] Therefore, targeting ACE2 is an important pharmacological intervention for a SARS-CoV-2 infection. […] In this review, we described the two-way switch role of ACE2 in the treatment of novel coronavirus pneumonia and underlying comorbidities, and discussed the potential effect of the ACE inhibitor and angiotensin receptor blocker on a hypertension patient with the SARS-CoV-2 infection. […] In addition, we analyzed the S-protein-binding site on ACE2 and suggested that blocking hot spot-31 and hot spot-353 on ACE2 could be a therapeutic strategy for preventing the spread of SARS-CoV-2. […] Besides, the recombinant ACE2 protein could be another potential treatment option for SARS-CoV-2 induced acute severe lung failure. […] This review could provide beneficial information for the development of anti-SARS-CoV-2 agents via targeting ACE2 and the clinical usage of renin-angiotensin system (RAS) drugs for novel coronavirus pneumonia treatment.
33397429 Use of anticoagulants (e.g., warfarin) and ACE inhibitors (e.g., captopril). […] Control groups: The outpatient group will receive hydroxychloroquine sulfate (Amin Pharmaceutical Company, Iran) at a dose of 400 mg twice a day for the first day and 200 mg twice a day for seven subsequent days.
33398362 The angiotensin-converting enzyme 2 (ACE2) has been proven to be used by SARS-CoV-2 for host cell entry. […] Considering that angiotensin receptor blockers and ACE inhibitors (ACEIs) upregulate the expression of ACE2 in animal studies, there may be a concern about whether these drugs may increase COVID-19 susceptibility and severity. […] Recently, there has been a debate among clinicians about whether to continue or to stop ACEIs and angiotensin receptor blockers in the context of COVID-19. […] Favorable effects include blocking the ACE2 receptors, preventing viral entry into the heart and lungs, and protecting against lung injury in COVID-19. […] Adverse effects include a possible retrograde feedback mechanism that upregulates ACE2 receptors.
33398633 Angiotensin-converting enzyme 2 (ACE-2), a human receptor that facilitates entry of SARS-CoV-2, serves as a prominent target for drug discovery. […] In the present study, we have applied the bioinformatics approach for screening of a series of bioactive chemical compounds from Himalayan stinging nettle (Urtica dioica) as potent inhibitors of ACE-2 receptor (PDB ID: 1R4L). […] Among them, β-sitosterol was found with the highest binding affinity - 12.2 kcal/mol and stable interactions with the amino acid residues present on the active site of the ACE-2 receptor.
33399743 The ACE 2 receptor is the main receptor of SARS-CoV-2, with evidence of its high presence in the intestine, colon and cholangiocytes, and, in smaller proportion, in hepatocytes. […] The characteristics of this virus include the S (Spike) protein that binds very stably to the ACE-2 receptor and, at the same time, SARS-CoV-2 produces dysbiosis and alterations in the gut-lung axis.
33404363 In particular, we now better understand the complexity of the renin-angiotensin-aldosterone system (RAAS) and the important role of angiotensin converting enzyme (ACE)-2 in viral binding.
33412235 Based on the traditional medicinal knowledge, we made an attempt through molecular docking analysis to explore the phytochemical constituents of three most commonly used Indian herbs in ‘steam inhalation therapy’ against well recognized viral receptor proteins. , ACE-2, spike glycoprotein and RdRp.
33412367 In this context, the use of nutraceuticals appears to be a potential panacea. […] The ability of algae-based nutraceuticals, mainly Spirulina, to boost immunity against viral diseases has already been reported clinically. […] Spirulina-based nutraceuticals boost the adaptive and innate immunity, and bioactive compounds, such as angiotensin-converting enzyme (ACE) inhibitor peptides, phycobiliproteins, sulfated polysaccharides, and calcium-Spirulan, can serve as antiviral agents. […] This review focuses on the potential role of algal nutraceuticals as immune boosters to combat the human coronavirus and other viral diseases. […] The potential use of Spirulina-based nutraceuticals for combating COVID-19, its mechanism, and future directions have also been discussed.
33416918 The aim of this study was to investigate the impact of concomitant long-term medication-with a focus on ACE inhibitors and oral anticoagulation-on clinical outcomes in patients hospitalized with coronavirus disease 2019. […] ACE inhibitors did not impact outcomes.
33417221 Also, occupation of the angiotensin-converting enzyme 2 (ACE-2) with the virus may lead to a decline in ACE-2 activity, which acts as a neuroprotective factor. […] Furthermore, acute respiratory distress syndrome (ARDS) and septicemia induce hypoxemia and hypoperfusion, which are locally exacerbated due to the hypercoagulable state and micro-thrombosis in brain vessels, leading to oxidative stress and neurodegeneration.
33423311 The receptor binding domain (RBD) which is involved in the interactions with human angiotensin-converting enzyme-2 (ACE-2) receptor and causes infection leading to the COVID-19 disease comprised 44 mutations that included residues within 3.2 Å interacting distance from the ACE-2 receptor.
33423528 We examined whether COVID-19 risk differs according to antihypertensive drug class in patients treated by ACE (angiotensin-converting enzyme) inhibitors and angiotensin receptor blockers (ARBs) compared with calcium channel blockers (CCBs). […] Three exclusive cohorts of prevalent ACE inhibitors, ARB and CCB users, aged 18 to 80 years, from the French National Health Insurance databases were followed from February 15, 2020 to June 7, 2020. […] In a population of almost 2 million hypertensive patients (ACE inhibitors: 566 023; ARB: 958 227; CCB: 358 306) followed for 16 weeks, 2338 were hospitalized and 526 died or were intubated for COVID-19. […] ACE inhibitors and ARBs were associated with a lower risk of COVID-19 hospitalization compared with CCBs (hazard ratio, 0.74 [95% CI, 0.65-0.83] and 0.84 [0.76-0.93], respectively) and a lower risk of intubation/death. […] Risks were slightly lower for ACE inhibitor users than for ARB users. […] This large observational study may suggest a lower COVID-19 risk in hypertensive patients treated over a long period with ACE inhibitors or ARBs compared with CCBs.
33426593 SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE-2) as the entry receptor into host cell. […] ACE-2, a type-I transmembrane metallocarboxypeptidase, is a critical regulator of the renin-angiotensin system. […] The entry of SARS-CoV-2 within host cells results in a reduced availability of ACE-2 on the host cell surface followed by significant downregulation of ACE-2 gene expression. […] As ACE-2 is a well-known cardio-protective molecule, its downregulation could result in severe cardiac disorders.
33426604 Since SARS-CoV-2 binds to angiotensin-converting enzyme 2 (ACE2) for entering into host cells, to target COVID-19 from therapeutic angle, we engineered a hexapeptide corresponding to the ACE2-interacting domain of SARS-CoV-2 (AIDS) that inhibits the association between receptor-binding domain-containing spike S1 and ACE-2. […] Therefore, selective targeting of ACE2-to-SARS-CoV-2 interaction by wtAIDS may be beneficial for COVID-19.
33435547 Accumulating evidence supports that COVID-19 is not merely a respiratory illness per se, but potentially affects other organ systems including the placenta. […] SARS-CoV-2 gains access to human cells via angiotensin-converting enzyme 2 (ACE-2). […] The abundance of ACE-2 on the placental cell surface, especially the syncytiotrophoblasts, could potentially contribute to vertical transplacental transmission to the fetus following maternal COVID-19 infection. […] Intriguingly, despite the placentas being tested positive for SARS-CoV-2, there are very few newborns that manifest virus-induced diseases. […] The protective effects of the placental barrier to viral infection, limiting the spread of the virus to newborn infants, remain a mystery. […] In this review, we summarize the pathological features manifested in placenta due to COVID-19 maternal infection that have been previously reported, and relate them to the possible disease manifestation. […] The potential mechanistic pathways associated with transplacental viral transmission and adverse pregnancy outcomes are also discussed.
33435929 COVID-19 is a two-phase disease being marked by (phase 1) increased virus transmission and infection rates due to the wide expression of the main infection-related ACE2, TMPRSS2 and CTSB/L human genes in tissues of the respiratory and gastrointestinal tract, as well as by (phase 2) host- and probably sex- and/or age-specific uncontrolled inflammatory immune responses which drive hyper-cytokinemia, aggressive inflammation and (due to broad organotropism of SARS-CoV-2) collateral tissue damage and systemic failure likely because of imbalanced ACE/ANGII/AT1R and ACE2/ANG(1-7)/MASR axes signaling.
33436481 We propose possible synergistic pathophysiologic mechanisms for enterocolitis complicating severe COVID-19 infection: (1) T lymphocyte depletion and immune response dysregulation, (2) use of immunomodulators in the management of severe COVID-19 infection and (3) high concentration of ACE-2 receptors for COVID-19 virus in the gastrointestinal tract.
33437144 There are still gaps in the elucidation of the pathways involved in the loss of smell caused by SARS-CoV-2; however, the great affinity of the virus for ACE-2 receptors, which are present in large quantities in the nasal cavity and olfactory bulb, has been considered.
33438525 The affinity and essential residues involving in the Enf binding to the S2 protein of SARS-CoV-2, HIV-1 gp41 protein and angiotensin-converting enzyme 2 (ACE-2) as a negative control, was evaluated using molecular docking.
33442728 The entry and infection strategy of SARS-CoV-2 in a host cell is raised by an amazing way of angiotensin-converting enzyme (ACE) 2 (ACE2) receptor recognition and imbalance of ACE/ACE2 in various organs, especially in the lungs. […] Here it has been discussed the role of interferon and protease during the receptor recognition (begining of infection) and followed by the impact of cytokine and hypoxia in the context of the balance of ACE/ACE2. […] It has also very concisely delineated the biochemistry and mechanism of ACE/ACE2 balance in different stages of infection and its role in comorbidity.
33443816 SARS-CoV-2, the virus responsible for the global coronavirus disease (COVID-19) pandemic, attacks multiple organs of the human body by binding to angiotensin-converting enzyme 2 (ACE2) to enter cells. […] ACE2 is not only a functional receptor of COVID-19 but also an important endogenous antagonist of the renin-angiotensin system (RAS). […] A large number of studies have shown that ACE2 can reverse myocardial injury in various cardiovascular diseases (CVDs) as well as is exert anti-inflammatory, antioxidant, anti-apoptotic and anticardiomyocyte fibrosis effects by regulating transforming growth factor beta, mitogen-activated protein kinases, calcium ions in cells and other major pathways. […] The ACE2/angiotensin-(1-7)/Mas receptor axis plays a decisive role in the cardiovascular system to combat the negative effects of the ACE/angiotensin II/angiotensin II type 1 receptor axis. […] However, the underlying mechanism of ACE2 in cardiac protection remains unclear. […] Some approaches for enhancing ACE2 expression in CVDs have been suggested, which may provide targets for the development of novel clinical therapies. […] In this review, we aimed to identify and summarize the role of ACE2 in CVDs.
33445824 Recent evidence has shown no harm associated with the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) in patients with coronavirus disease 2019 (COVID-19). […] We sought to further clarify the possible association between ACEI/ARB use and the risk of poor clinical outcomes of COVID-19. […] From the completely enumerated COVID-19 cohort in Korea, we identified 1,290 patients with hypertension, of whom 682 had and 603 did not have records of ACEI/ARB use during the 30-day period before their COVID-19 diagnosis. […] We used inverse probability of treatment weighting (IPTW) to mitigate selection bias, and a Poisson regression model to estimate the relative risks (RRs) and 95% confidence intervals (CIs) for comparing outcomes between ACEI/ARB users and non-users. […] Compared to non-use, ACEI/ARB use was associated with lower clinical outcomes (IPTW-adjusted RR, 0.60; 95% CI, 0.42 to 0.85; p=0.005). […] For individual outcomes, ACEI/ARB use was not associated with all-cause mortality (IPTW-adjusted RR, 0.62; 95% CI, 0.35 to 1.09; p=0.097) or respiratory events (IPTW-adjusted RR, 0.99; 95% CI, 0.84 to 1.17; p=0.904). […] Subgroup analysis showed a trend toward a protective role of ACEIs and ARBs against overall outcomes in men (IPTW-adjusted RR, 0.84; 95% CI, 0.69 to 1.03; pinteraction=0.008) and patients with pre-existing respiratory disease (IPTW-adjusted RR, 0.74; 95% CI, 0.60 to 0.92; pinteraction=0.002). […] We present clinical evidence to support continuing ACE/ARB use in COVID-19 patients with hypertension based on the completely enumerated Korean cohort.
33446983 Intravenous immunoglobulin is rich in viral immunoglobulin G (IgG), competitively binds Fcy receptor, preventing SARS-CoV-2 spike protein from attaching to the angiotensin-converting enzyme 2 (ACE 2) receptor, inhibiting viral entry into the cell.
33457429 were done to find out whether these compounds could inhibit the receptor binding of SARS-CoV-2 spike protein (S protein) as well as the angiotensin-converting enzyme 2 (ACE-2), as evidenced from their docking into binding/active sites. have significant affinity in silico to spike protein of virus and ACE-2 receptor in the host. may have good potential in reducing viral load and shedding of SARS-CoV-2 in the nasal passages.
33458630 Angiotensin-converting enzyme 2 (ACE2) has been identified as a functional receptor for the SARS-CoV-2 virus, and it is associated with the cardiovascular system. […] Observational data support international cardiovascular societies’ recommendations to not discontinue ACE inhibitor/angiotensin-receptor blocker therapy in patients with guideline indications for fear of the increased risk of SARS-CoV-2 infection, severe disease, or death.
33458761 Some recent research shows the SARS-CoV-\(2\) uses the angiotensin converting enzyme-\(2\) (ACE-\(2\)) as a receptor to infect human susceptible cells. […] The ACE2 gene is expressed in many human tissues, including intestine, testis, kidneys, heart and lungs. […] ACE2 usually converts Angiotensin I in the renin-angiotensin-aldosterone system to Angiotensin II, which affects blood pressure levels. […] ACE inhibitors prescribed for cardiovascular disease and hypertension may increase the levels of ACE-\(2\), although there are claims that such medications actually reduce lung injury caused by COVID-\(19\).
33459225 The angiotensin-converting enzyme 2 (ACE2), a carboxypeptidase that degrades angiotensin II into angiotensin 1-7, has been identified as a potent receptor for SARSCoV-2. […] In the last decades, ACE inhibition has assumed a central role in reducing cardiovascular and renal events. […] However, with the advent of COVID-19, attention has been turned to ACE-2 as a possible target to reduce virus binding to different human cells. […] This review aims to discuss recent developments related to medicinal properties of natural compounds as ACE/ACE-2 inhibitors, which should be highlighted in the future development of studies looking for modulators in SARSCoV-2 infection. […] Data show that bioactive compounds isolated from several natural products act by inhibiting ACE/ACE2, which changes the entire axis of this system. […] Of the compounds addressed in this review, 7 phenolic compounds, including quercetin, curcumin, naringenin, luteolin, hesperidin, mangiferin, and gallic acid showed binding affinity with molecular ACE-2 target in silico, and 1, esculetin, decreased ACE-2 expression in vivo. […] Regarding terpenoids and alkaloids, nimbin, withaferin A, andrographolide, zingiberene and, berberine, piperine and thebaine, respectively, showed binding affinity with molecular ACE-2 target in silico. […] These findings reinforce the need for future preclinical and clinical studies on these compounds and specific inhibitory effects on ACE-2 of all the other compounds described herein only as nonspecific ACE inhibitors. […] It is important to mention that some natural compounds such as magnolol, resveratrol, rosmarinic acid, tanshinone IIA, and nicotine have also demonstrated the potential to increase the activity or expression of ACE-2, and could therefore aggravate SARS-CoV-2 infection.
33461019 The multifunctional protein angiotensin converting enzyme 2 (ACE2) is accepted as its primary target for entry into host cells. […] In its enzymatic function, ACE2, like its homologue ACE, regulates the renin-angiotensin system (RAS) critical for cardiovascular and renal homeostasis in mammals. […] Unlike ACE, however, ACE2 drives an alternative RAS pathway by degrading Ang-II and thus operates to balance RAS homeostasis in the context of hypertension, heart failure, and cardiovascular as well as renal complications of diabetes. […] Outside the RAS, ACE2 hydrolyzes key peptides, such as amyloid-β, apelin, and [des-Arg9]-bradykinin. […] In addition to its enzymatic functions, ACE2 is found to regulate intestinal amino acid homeostasis and the gut microbiome. […] Although the non-enzymatic function of ACE2 as the entry receptor for SARS-CoV-2 has been well established, the contribution of enzymatic functions of ACE2 to the pathogenesis of COVID-19-related lung injury has been a matter of debate.
33461499 Cox proportional hazards modeling for time to death demonstrated a significantly high ratio for COPD/Asthma, and favorable effects on outcomes for pre-admission ACE inhibitors and ARBs. […] Early dialysis and pre-admission intake of ACE inhibitors/ARBs improved patient outcomes.
33462852 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects the host by binding to angiotensin-converting enzyme 2 (ACE2). […] The role of ACE2 in the pathophysiology of coronavirus disease 2019 (COVID-19) is a topic of debate, with clinical and experimental evidence indicating a multifaceted relationship between ACE2 activity and disease severity. […] Here, we review the mechanisms by which the peptidergic substrates and products of ACE and ACE2 contribute to physiological and pathophysiological processes and hypothesise how down-regulation of ACE2 by SARS-CoV-2 cellular entry disrupts homeostasis. […] A better understanding of the endocrinology of the disease, in particular the neuroendocrinology of ACE2 during COVID-19, may contribute to the timely design of new therapeutic strategies, including the regulation of ACE2 itself by steroid hormones, to ameliorate the severity of COVID-19.
33463480 In this study, we focused Adathoda primary active alkaloid vasicine efficacy against coronavirus infectious symptoms, evaluated by in Silico screening studies on virus proteins ACE 2 Receptor, 3CL protease and Spike protein SARS HR1 motif using PyRx tool and AutoDoc 1.5.6. […] Based on PyRx results, Vasicine with ACE 2 Receptor shown higher docking affinity score -7.1 K/cal respectively when compared to other virus proteins. […] Based on the results with available literature Adathoda could be a drug helpful in relieving symptoms in non COVID cases those who were quarantined or in lockdown pace thereby reducing pandemic panic and in confirmed asymptomatic or mild cases.
33464168 Angiotensin-converting enzyme (ACE)2 is the receptor for SARS-CoV-2. […] Alterations in the ACE-to-ACE2 ratio have been implicated in renal diseases. […] Clinicians should ensure early and effective cardiometabolic control for all patients to ameliorate the compensatory elevation of ACE2 and alterations in the ACE-to-ACE2 ratio.
33469197 Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 infection, exploits angiotensin-converting enzyme 2 (ACE 2) to induce ED and hypertension, thereby mimicking angiotensin II-mediated PE in severe cases of infection. […] Upregulated ACE 2 in pregnancy is a possible risk factor for SARS-CoV-2 infection and subsequent PE development.
33471683 ACE = angiotensin-converting enzyme; AI = adrenal insufficiency; ARB = angiotensin receptor blocker; ARDS = acute respiratory disease syndrome; COVID-19 = coronavirus disease 2019; CPAP = continuous positive airway pressure; DI = diabetes insipidus; DM = diabetes mellitus; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.
33472206 Immunohistochemical staining was performed using antibodies against fibrin, cleaved caspase 3 and ACE-2. […] In control eyes, ACE-2 was detectable in the conjunctiva, cornea, retina and in the choroidea, and displayed significantly lower amounts of stained cells as in COVID-19 eyes. […] A possible viral spread to the endothelial cells via ACE-2 provides one pathophysiological explanation. […] The expression of ACE-2 receptors in the conjunctiva hints towards its susceptibility to infection.
33472675 SARS-CoV-2, the virus that causes COVID-19, enters the cells through a mechanism dependent on its binding to angiotensin-converting enzyme 2 (ACE2), a protein highly expressed in the lungs. […] The putative viral-induced inhibition of ACE2 could result in the defective degradation of bradykinin, a potent inflammatory substance. […] One hundred eighty eligible patients will be randomly assigned in a 1:1:1 ratio to receive either the inhibitor of C1e/kallikrein 20 U/kg intravenously on day 1 and day 4 plus standard care; or icatibant 30 mg subcutaneously, three doses/day for 4 days plus standard care; or standard care alone, as recommended in the clinical trials published to date, which includes supplemental oxygen, non-invasive and invasive ventilation, antibiotic agents, anti-inflammatory agents, prophylactic antithrombotic therapy, vasopressor support, and renal replacement therapy. […] Accumulation of bradykinin in the lungs is a common side effect of ACE inhibitors leading to cough. […] In animal models, the inactivation of ACE2 leads to severe acute pneumonitis in response to lipopolysaccharide (LPS), and the inhibition of bradykinin almost completely restores the lung structure.
33474994 Angiotensin-converting enzyme (ACE)/Angiotensin (Ang) II pathway has crucial regulatory effects on circulatory hemostasis and immune responses. […] The aim of this study is to investigate the serum ACE activity and its correlation with clinical features and the disease severity in patients with COVID-19. […] The serum ACE activity was evaluated with an autoanalyzer based on a spectrophotometric method. […] The median serum ACE activity of patients and controls (38.00 [IQR 21] U/L and 32.00 [IQR 24] U/L, respectively) and of between patients grouped by disease severity (38.5 [IQR 19], 36 [IQR 25], and 38 [IQR 22] U/L, asymptomatic, mild and severe pneumonia group, respectively) were similar. […] There was no correlation between the serum ACE activity and conventional inflammatory markers. […] In this study, we did not find an association between serum ACE activity and COVID-19 and serum ACE activity on admission did not reflect disease severity.
33479758 The key link between renin-angiotensin system (RAS) and COVID-19 is ACE2 (angiotensin-converting enzyme 2), which acts as a double-edged sword, because ACE2 increases the tissue anti-inflammatory response but it is also the entry receptor for the virus. […] There is an important controversy on several drugs that regulate RAS activity and possibly ACE2, and are widely used, particularly by patients most vulnerable to severe COVID-19. […] In the lung of healthy rats, we observed that candesartan (an angiotensin type-1, AT1, receptor blocker; ARB) and captopril (an ACE inhibitor; ACEI) up-regulated expression of tissue ACE2 and RAS anti-inflammatory axis receptors (AT2 and Mas receptors). […] Treatment of cultures of human type-II pneumocytes with candesartan or captopril induced up-regulation of ACE2 expression in cells. […] Treatment with viral spike protein induced a decrease in full-length (i.e. transmembrane) ACE2, an increase in levels of a short intracellular ACE2 polypeptide and an increase in ADAM17 activity in cells, together with an increase in levels of soluble ACE2 and major proinflammatory cytokines in the culture medium. […] The results suggest that these drugs increase ACE2 levels and promote the anti-inflammatory RAS axis in the lung. […] Furthermore, possible up-regulation of viral entry by the drug-induced increase in expression of transmembrane ACE2 is counteracted by additional mechanisms, particularly by drug-induced inhibition of ADAM17 activity.
33486116 Angiotensin-converting enzyme 2 (ACE-2) facilitates the access of SARS-CoV-2 to cells. […] Therapeutic agents acting on the renin-angiotensin system (RAS) might be able to modulate the concentration of ACE-2 and the various components of the system. […] Here, we discuss current pharmacological, molecular, and clinical evidence to investigate whether drugs acting on RAS with modulation of the ACE-2 concentration have added value in combating SARS-CoV-2 infection. […] We also highlight the possible deleterious action of the ACE/Ang-II/AT-1r axis and possible beneficial role of the ACE-2/Ang 1-7/MasR axis in acute respiratory distress syndrome (ARDS) caused by SARS-CoV-2, discussing the possibility of addressing the various RAS components with drug treatments to improve clinical outcomes.
33489841 The widespread presence of ACE-2 receptors on various tissues suggests scope for direct viral infection.
33495677 This novel virus is known to gain entry through the ACE 2 receptor of pulmonary epithelial cells lining the respiratory tract.
33495692 This approach relies on targeting the virus using ACE-2-functionalized gold nanorods (AuNRs) followed by irradiation with near-infrared (NIR) light for the selective eradication of SARS-CoV-2 without off-target effects, i.e., targeted plasmonic photothermal therapy. […] Using discrete dipole approximation (DDA), we quantitatively determined the efficiency of AuNRs (31 nm × 8 nm) in absorbing NIR when present at different orientations relative to one another on the surface of the virus.
33497420 Commercial and ‘in-house’ serological assays were used to measure IgG antibodies against different SARS-CoV-2 structural antigens-Spike (S) S1 sub-unit and Nucleocapsid protein (NP)-and to assess the potential for virus neutralisation mediated specifically by inhibition of binding between the viral attachment protein (S protein) and cognate receptor (ACE-2). […] The earliest IgG antibodies produced by all patients included those that recognised the S protein receptor-binding domain (RBD) and were capable of inhibiting binding to ACE-2.
33501506 In a more preliminary analysis, the metabolism of the frontal cluster which included the olfactory gyrus was worse in the 7 patients treated by ACE drugs for high blood pressure (p = 0.032), and better in the 3 patients that had used nasal decongestant spray at the infectious stage (p < 0.001). […] The hypometabolism of the frontal cluster, which included the olfactory gyrus, seems to be linked to ACE drugs in patients with high blood pressure, with also a better metabolism of this olfactory region in patients using nasal decongestant spray, suggesting a possible role of ACE receptors as an olfactory gateway for this neurotropism.
33503627 No differences in potential predisposing factors were found between asymptomatic and symptomatic patients except for a lower use of ACE inhibitors among asymptomatic patients.
33504565 The association of ACE inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) with disease severity of patients with COVID-19 is still unclear. […] We conducted a systematic review and meta-analysis to investigate if ACEI/ARB use is associated with the risk of mortality and severe disease in patients with COVID-19. […] We searched all available clinical studies that included patients with confirmed COVID-19 who could be classified into an ACEI/ARB group and a non-ACEI/ARB group up until 4 May 2020. […] ACEI/ARB therapy was not associated with increased risk of all-cause mortality or severe manifestations in patients with COVID-19. […] ACEI/ARB therapy can be continued without concern of drug-related worsening in patients with COVID-19.
33506503 ACE inhibitors (ACEi) and angiotensin receptor blockers (ARBs) are standard-of-care treatments for hypertension and diabetes, common comorbidities among hospitalized COVID-19 patients. […] Their use in the setting of COVID-19 has been heavily debated due to potential interactions with ACE2, an enzyme that links the pro- and anti-inflammatory arms of the in the renin angiotensin system, but also the entryway by which SARS-CoV-2 invades cells. […] ACE2 expression is altered by age, hypertension, diabetes, and the virus itself. […] This study integrated available information about the RAAS system and effects of SARS-CoV-2 and its comorbidities on ACE2 into a mechanistic mathematical model and aimed to quantitatively predict effects of ACEi/ARBs on the RAAS pro-/anti-inflammatory balance. […] RAAS blockade prior to SARS-CoV-2 infection is predicted to increase the mas/AT1 receptor occupancy ratio up to 20-fold, indicating that in patients already taking an ACEi/ARB before infection, the anti-inflammatory arm is already elevated while the pro-inflammatory arm is suppressed. […] Predicted pro-inflammatory shifts in the mas-AT1 ratio due to ACE2 downregulation by SARS-CoV-2 were small relative to anti-inflammatory shifts induced by ACEi/ARB. […] Predicted effects of changes in ACE2 expression with comorbidities of diabetes, hypertension, or aging on mas-AT1 occupancy ratio were also relatively small. […] Lastly, predicted changes in the Ang(1-7) production rate with ACEi/ARB therapy, comorbidities, or infection were all small relative to exogenous Ang(1-7) infusion rates shown experimentally to protect against acute lung injury, suggesting that any changes in the ACE2-Ang(1-7)-mas arm may not be large enough to play a major role in COVID-19 pathophysiology.
33506944 On the contrary, there was no difference in the proportion of those receiving ACE inhibitors (ACE-I) (21.2% vs. 
33511992 The two axes of the renin-angiotensin system include the classical ACE/Ang II/AT1 axis and the counter-regulatory ACE2/Ang-(1-7)/Mas1 axis. […] ACE2 is a multifunctional monocarboxypeptidase responsible for generating Ang-(1-7) from Ang II. […] ACE2 is important in the vascular system where it is found in arterial and venous endothelial cells and arterial smooth muscle cells in many vascular beds. […] Among the best characterized functions of ACE2 is its role in regulating vascular tone. […] ACE2 through its effector peptide Ang-(1-7) and receptor Mas1 induces vasodilation and attenuates Ang II-induced vasoconstriction. […] In endothelial cells activation of the ACE2/Ang-(1-7)/Mas1 axis increases production of the vasodilator’s nitric oxide and prostacyclin’s and in vascular smooth muscle cells it inhibits pro-contractile and pro-inflammatory signaling. […] Endothelial ACE2 is cleaved by proteases, shed into the circulation and measured as soluble ACE2. […] Plasma ACE2 activity is increased in cardiovascular disease and may have prognostic significance in disease severity. […] In addition to its enzymatic function, ACE2 is the receptor for severe acute respiratory syndrome (SARS)-coronavirus (CoV) and SARS-Cov-2, which cause SARS and coronavirus disease-19 (COVID-19) respectively. […] ACE-2 is thus a double-edged sword: it promotes cardiovascular health while also facilitating the devastations caused by coronaviruses. […] Mechanisms linking COVID-19 and cardiovascular disease are unclear, but vascular ACE2 may be important. […] This review focuses on the vascular biology and (patho)physiology of ACE2 in cardiovascular health and disease and briefly discusses the role of vascular ACE2 as a potential mediator of vascular injury in COVID-19.
33513487 The SARS-COV-2 virus is triggered by binding to the Angiotensin-Converting Enzyme 2 (ACE 2) inhibitor, which is vital in cardiovascular diseases and the immune system, especially in conditions such as cerebrovascular, hypertension, and diabetes. […] The current dataset contains age, gender, chronic disease (hypertension, diabetes, renal, cardiovascular, etc.), some enzymes (ACE, angiotensin II receptor blockers), and COVID-19 severity, which are used to predict death status using deep learning and machine learning approaches (random forest, k-nearest neighbor, extreme gradient boosting [XGBoost]).
33514423 SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) as an initial mediator for viral attachment and host cell invasion. […] ACE2 is widely distributed in the human tissues including the cell surface of lung cells which represent the primary site of the infection. […] Inhibiting or reducing cell surface availability of ACE2 represents a promising therapy for tackling COVID-19. […] In this context, most ACE2-based therapeutic strategies have aimed to tackle the virus through the use of angiotensin-converting enzyme (ACE) inhibitors or neutralizing the virus by exogenous administration of ACE2, which does not directly aim to reduce its membrane availability. […] However, through this review, we present a different perspective focusing on the subcellular localization and trafficking of ACE2. […] Membrane targeting of ACE2, and shedding and cellular trafficking pathways including the internalization are not well elucidated in literature. […] Therefore, we hereby present an overview of the fate of newly synthesized ACE2, its post translational modifications, and what is known of its trafficking pathways. […] In addition, we highlight the possibility that some of the identified ACE2 missense variants might affect its trafficking efficiency and localization and hence may explain some of the observed variable severity of SARS-CoV-2 infections. […] Moreover, an extensive understanding of these processes is necessarily required to evaluate the potential use of ACE2 as a credible therapeutic target.
33519145 Thus, this study examined the potency of a natural medicinal product, Sulawesi propolis compounds produced by Tetragonula sapiens, inhibiting angiotensin-converting activity enzyme-2 (ACE-2), a receptor of SARS-CoV-2 in the human body. […] In this study, molecular docking was done to analyze the docking scores as the representation of binding affinity and the interaction profiles of propolis compounds toward ACE-2. […] The results illustrated that by considering the docking score and the presence of interaction with targeted sites, five compounds, namely glyasperin A, broussoflavonol F, sulabiroins A, (2S)-5,7-dihydroxy-4’-methoxy-8-prenylflavanone and isorhamnetin are potential to inhibit the binding of ACE-2 and SARS-CoV-2, with the docking score of -10.8, -9.9, -9.5, -9.3 and -9.2 kcal/mol respectively.
33520014 One of the ways for prevention of Covid-19 is by disabling its spike protein which results in inhibiting its binding with angiotensin-converting enzyme 2 (ACE-2).
33520683 Among them, quercetin, one of the most abundant of plant flavonoids, is proposed as a lead candidate with its ability on the virus side to inhibit SARS-CoV spike protein-angiotensin-converting enzyme 2 (ACE2) interaction, viral protease and helicase activities, as well as on the host cell side to inhibit ACE activity and increase intracellular zinc level.
33524563 Blocking of human angiotensin-converting enzyme 2 (ACE-2) receptor, the binding site of SARS-CoV-2 spike protein, an effective strategy to discover a drug for COVID-19. […] Herein we have selected 24 anti-bacterial and anti-viral drugs and made a comprehensive analysis by screened them virtually against ACE-2 receptor to find the best blocker by molecular docking and molecular dynamics studies. […] Furthermore, MD study for 10 ns and evaluation of parameters like RMSD, RMSF, radius of gyration, solvent accessible surface area analysis confirmed that CPM effectively binds and blocks ACE-2 receptor efficiently.
33525440 During transmission, the renin-aldosterone-angiotensin-system (RAAS) is involved with the spike protein of SARS-CoV-2, attaching to its natural receptor angiotensin-converting enzyme 2 (ACE 2) in host cells.
33526007 The SARS-CoV-2 receptor-binding spike domain associates itself with human angiotensin-converting enzyme 2 (ACE-2) receptors. […] Development of vaccine by several leader of pharmaceutical groups still under trial or waiting for approval for mass inoculation.
33526121 While scientist are working to find a vaccine, current epidemiological data shows that the most common comorbidities for patients with the worst prognosis, hypertension and diabetes, are often treated with angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). […] BODY: Both ACE inhibitors and ARBs induce overexpression of the angiotensin converting enzyme 2 (ACE-2) receptor, which has been identified as the main receptor used by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to enter into the alveolar cells of the lungs. […] While cannabinoids are known to reduce hypertension, the studies testing the hypotensive effects of cannabinoids never addressed their effects on ACE-2 receptors. […] Since there are around 192 million people using cannabis worldwide, we believe that the mechanism underlying the hypotensive properties of cannabinoids should be urgently studied to understand if they can also lead to ACE-2 overexpression as other antihypertensive drugs do.
33533405 The existence of RAS is well established in metabolic organs, including pancreas, liver, skeletal muscle, and adipose tissue, where activation of angiotensin-converting enzyme (ACE) - angiotensin II pathway contributes to the impairment of insulin secretion, glucose transport, fat distribution, and adipokines production. […] However, the activation of angiotensin-converting enzyme 2 (ACE2) - angiotensin (1-7) pathway, a novel branch of the RAS, plays an opposite role in the ACE pathway, which could reverse these consequences by improving local microcirculation, inflammation, stress state, structure remolding, and insulin signaling pathway. […] Interestingly, ACE2 is the receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is threating public health worldwide. […] Here, we summarize the latest pharmacological and genetic tools on regulating ACE/ACE2 balance and highlight the beneficial effects of the ACE2 pathway axis hyperactivity on glycolipid metabolism, as well as the thermogenic modulation.
33539316 Objective While evidence on the interface between severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection and the renin-angiotensin-aldosterone-system (RAAS) is accumulating, clinical data on RAAS peptide alteration among coronavirus disease-19 (COVID-19) patients is missing. […] 207.9pmol/l, -58.5% [95%CI -71.4% to -45.6%]), there was no difference of angiotensin-converting enzyme (ACE) and ACE2 plasma activity between the groups.
33544293 All appraised studies in synergism showed that mortality outcomes were not augmented with the employment of either ACE inhibitor or ARB in subjects.
33544720 These top-ranked drugs include ACE-inhibitors, monoclonal antibodies (e.g., anti-IFNγ, anti-TNFα, anti-IL12, anti-IL1β, anti-IL6), and thrombin inhibitors.
33547593 Though CoV-2 Spike does not favorably interact with murine ACE2 receptor, modification of murine SARS-CoV2 binding domain or development of transgenic ACE-2 knock-in mice might help in mediating consequential infection and understanding human CoV2 pathogenesis in murine models.
33550782 Evidence suggest that the virus could enter the CNS through angiotensin-converting enzyme-2 (ACE-2) receptor, neuronal transport, haematogenous route, and nasal route via olfactory bulb, cribriform plate, and propagates through trans-synaptic signalling, and shows retrograde movement into the CNS along nerve fiber. […] COVID-19 induces CNS inflammation and neurological degenerative damage through a diverse mechanism which includes ACE-2 receptor damage, cytokine-associated injury or cytokine storm syndrome, secondary hypoxia, demyelination, blood-brain barrier disruption, neurodegeneration, and neuroinflammation.
33558635 Despite unprecedented global efforts to rapidly develop SARS-CoV-2 treatments, in order to reduce the burden placed on health systems, the situation remains critical. […] We present a rapid method for nanobody isolation that includes an optimized immunization regimen coupled with VHH library E. coli surface display, which allows single-step selection of Nanobodies using a simple density gradient centrifugation of the bacterial library. […] The selected single and monomeric Nanobody, W25, binds to the SARS-CoV-2 S RBD with sub-nanomolar affinity and efficiently competes with ACE-2 receptor binding.
33559733 A potential mechanism of DIR to HA fillers in COVID-19 related cases is binding and blockade of angiotensin 2 converting enzyme receptors (ACE2), which are targeted by the SARS-CoV-2 virus spike protein to gain entry into the cell. […] Spike protein interaction with dermal ACE2 receptors favors a pro-inflammatory, loco-regional TH1 cascade, promoting a CD8+T cell mediated reaction to incipient granulomas, which previously formed around residual HA particles. […] Management to suppress the inflammatory response in the native COVID-19 case required high-dose corticosteroids (CS) to suppress inflammatory pathways, with concurrent ACE2 upregulation, along with high-dose intralesional hyaluronidase to dissolve the inciting HA filler. […] With regards to the two vaccine related cases; in the mRNA-1273 case, a low dose angiotensin converting enzyme inhibitor (ACE-I) was utilized for treatment, to reduce pro-inflammatory Angiotensin II.
33563197 Symptoms of COVID-19 may vary from mild (fever, dry cough, shortness of breath) to severe pneumonia-like respiratory symptoms as exacerbation of disease occurs. […] Unlike SARS-CoV, the SARS-CoV-2 has a higher binding affinity to ACE-2 receptors which signify its higher transmission rate from person to person. […] Even though ACE-2 is significant in the renin-angiotensin-aldosterone system (RAAS) regulation that exhibits protection to various organs, they play a significant role in COVID-19 disease pathogenesis. […] Viral interferences with the ACE-2 peptidase activity are found in SARS-CoV-2 infected patients leading to pro-inflammatory responses, hypertension and multi-organ damage. […] Angiotensin-converting enzyme-2 is constrained to a variety of organ systems but surface ACE-2 receptors on lung epithelia are largely affected, that lead to pathological alterations in lung histology which may progress to respiratory failure. […] The viral tropism mainly occurs by the attachment to the angiotensin-converting enzymes-2 receptors in the host cell, thus drugs targeting ACE-2 expressions may arise as the future therapeutic strategy to combat COVID-19 infections.The innovative approach of repurposing of drugs has shown temporary effectiveness to the rising pandemic. […] This article mainly focuses on the prominence of ACE-2 receptors which are expressed during the COVID infections and repurposing strategy of available drug therapies.
33576494 Here, we immunized cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) and α1,3-galactosyl-transferase (GGTA1) double knockout (DKO) pigs with the SARS-CoV-2 spike receptor-binding domain (RBD) to produce glyco-humanized polyclonal neutralizing antibodies (GH-pAb) lacking Neu5Gc and α-Gal epitopes. […] The IgG fraction purified and formulated following clinical Good Manufacturing Practices, named XAV-19, neutralized Spike/angiotensin converting enzyme-2 (ACE-2) interaction at a concentration < 1 μg/mL and inhibited infection of human cells by SARS-CoV-2 in cytopathic assays. […] We also found that pig GH-pAb Fc domains fail to interact with human Fc receptors, thereby avoiding macrophage dependent exacerbated inflammatory responses and a possible antibody-dependent enhancement (ADE).
33585201 Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infects humans through the angiotensin converting enzyme-2 (ACE-2) receptor expressed on many cells, including lymphocytes.
33593260 Breast cancer and COVID-19 share involvement of common comorbidities, hormonal signalling pathways, gender differences, rennin-angiotensin system (RAS), angiotensin-converting enzyme-2 (ACE-2), transmembrane protease serine 2 (TMPRSS2) and dipeptidyl peptidase-IV (DPP-IV). […] Increased expression of ACE2 and TMPRSS2 are being correlated with occurrence and severity of COVID-19, but higher expression of ACE2 and lower expression of TMPRSS2 are prognostic markers for overall and disease free survival in breast cancer. […] The ACE2 inhibitors and ibuprofen therapies for COVID-19 treatment may aggravate the clinical condition of the breast cancer patients through chemo-resistance and metastasis.
33593483 SARS-CoV-2 penetrates host cells through the angiotensin 2 conversion enzyme (ACE-2). […] ACE-2 is expressed in the lungs, heart, testicles, liver, gastrointestinal tract, etc. […] Pathological remodeling of the extracellular matrix caused by SARS-CoV-2 leads to fibrotic lesions of myocardial tissue.
33593784 Whether ACE inhibitors (ACEi) or angiotensin II receptor blocker (ARB) therapy should be continued, initiated or ceased in patients with COVID-19 is uncertain. […] Given the widespread use of ACEi/ARBs worldwide, guidance on the use of these drugs is urgently needed. […] This prospective meta-analysis aims to pool data from randomised controlled trials (RCTs) to assess the safety and efficacy of ACEi/ARB therapy in adults infected with SARS-CoV-2. […] RCTs will be eligible if they compare patients with COVID-19 randomised to ACEi/ARB continuation or commencement versuss no ACEi/ARB therapy; study duration ≥14 days; recruitment completed between March 2020 and May 2021. […] The results of our analysis can inform public health policy and clinical decision making regarding ACEi/ARB use in patients with COVID-19 on a global scale.