transmembrane serine protease 2

Gene Context Sentence

Table 2. Analysis of context sentence of TMPRSS2 gene in 392 abstracts.

PMID Gene Context Sentence
32142651 Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. […] A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option.
32165541 Here, we show that a TMPRSS2-expressing VeroE6 cell line is highly susceptible to SARS-CoV-2 infection, making it useful for isolating and propagating SARS-CoV-2. […] Our results reveal that, in common with SARS- and Middle East respiratory syndrome-CoV, SARS-CoV-2 infection is enhanced by TMPRSS2.
32246845 SARS-CoV-2 was reported to enter cells via binding to ACE2, followed by its priming by TMPRSS2. […] Here, we investigate ACE2 and TMPRSS2 expression levels and their distribution across cell types in lung tissue (twelve donors, 39,778 cells) and in cells derived from subsegmental bronchial branches (four donors, 17,521 cells) by single nuclei and single cell RNA sequencing, respectively. […] While TMPRSS2 is expressed in both tissues, in the subsegmental bronchial branches ACE2 is predominantly expressed in a transient secretory cell type.
32257537 Furthermore, the gene expression profile showed MSCs were ACE2- and TMPRSS2- which indicated MSCs are free from COVID-19 infection.
32276929 TMPRSS2 is both the most frequently altered gene in primary prostate cancer and a critical factor enabling cellular infection by coronaviruses, including SARS-CoV-2. […] The modulation of its expression by sex steroids could contribute to the male predominance of severe infections and given that TMPRSS2 has no known indispensable functions, and inhibitors are available, it is an appealing target for prevention or treatment of respiratory viral infections.
32278065 SARS-CoV uses the the angiotensin-converting enzyme 2 (ACE2) and the serine protease TMPRSS2 for S protein priming. […] ACE2 and TMPRSS2 are not only expressed in lung, but also in the small intestinal epithelia.
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.
32283006 Multiple non-neuronal cell types present in the olfactory epithelium express two host receptors, ACE2 and TMPRSS2 proteases, that facilitate SARS-CoV-2 binding, replication, and accumulation.
32285974 SARS-CoV-2 was reported to enter cells via binding to ACE2, followed by its priming by TMPRSS2. […] Here, we investigate ACE2 and TMPRSS2 expression levels and their distribution across cell types in lung tissue (twelve donors, 39,778 cells) and in cells derived from subsegmental bronchial branches (four donors, 17,521 cells) by single nuclei and single cell RNA sequencing, respectively. […] While TMPRSS2 is strongly expressed in both tissues, in the subsegmental bronchial branches ACE2 is predominantly expressed in a transient secretory cell type.
32293910 The virus uses the ACE2 receptor for internalization, aided by TMPRSS2 protease.
32306862 Human TMPRSS2 3D structure was first generated using homology modeling approach. […] Moreover, four promising inhibitors were identified against TMPRSS2; Rubitecan and Loprazolam drugs, and compounds ZINC000015988935 and ZINC000103558522.
32316719 Objective: Angiotensin converting enzyme 2 (ACE2) and Transmembrane serine protease 2 (TMPRSS2) are the key proteins for 2019-nCoV entry into host cells. […] To evaluate the potential infection risk of 2019-nCoV on ocular surface, we compared ACE2 and TMPRSS2 expression among different eye tissues. Methods: Experimental article. […] Real-time PCR was performed to quantify ACE2 and TMPRSS2 gene expression in conjunctiva, cornea, lacrimal gland, iris, lens, retina, lung, heart, kidney, and liver from male mice. […] Published transcriptome datasets were extracted to generate the expression comparasion of ACE2 and TMPRSS2 between human conjunctival and corneal tissues, and results were analyzed with Mann-Whitney U test. […] Results were analyzed using Student’s t-test. Results: The expression of ACE2 and TMPRSS2 genes were the highest in conjunctiva among all the six mice eye tissues explored. […] ACE2 and TMPRSS2 shared similar expression pattern with the staining concentrated in corneal epithelium, conjunctival epithelium and lacrimal gland serous cells. […] The expression level of human conjunctiva ACE2 and TMPRSS2 were significantly higher than that in the cornea (P=0.007), with 5.74-fold and 12.84-fold higher in the conjunctiva than in the corneal epithelium cells, which resembled the situation in mice. Conclusion: The observation of high-level ACE2 and TMPRSS2 expression in conjunctiva among the 6 eye tissues examined suggests that conjunctiva serves as an infection target tissue of 2019-nCoV. (Chin J Ophthalmol, 2020, 56:). 目的: 分析眼部组织新型冠状病毒侵染和激活关键蛋白人血管紧张素转换酶2(ACE2)和跨膜丝氨酸蛋白酶2(TMPRSS2)的表达情况,探讨新型冠状病毒在眼部的侵染基础。 […] 使用荧光定量PCR分析小鼠结膜、角膜、泪腺、虹膜、晶状体、视网膜ACE2基因和TMPRSS2基因表达情况,并与肺脏、心脏、肾脏、肝脏中两个基因的表达量进行比较。 […] 使用免疫组化染色分析了小鼠各组织中ACE2和TMPRSS2蛋白的分布和表达情况。 […] 另取山东省眼科研究所红十字眼库接收的符合捐献条件的志愿者角膜及结膜组织切片,与小鼠眼部ACE2蛋白和TMPRSS2蛋白表达进行验证比较。 […] 同时通过分析已发表的人眼部组织转录组数据库,比较人角膜和结膜中ACE2和TMPRSS2基因的表达情况。 […] 结果: 在小鼠6种眼部组织中,结膜ACE2基因和TMPRSS2基因表达量最高,但均低于肾脏和肺脏;ACE2和TMPRSS2蛋白阳性染色集中于结膜上皮、角膜上皮和泪腺腺泡。 […] 与小鼠相似,人结膜ACE2和TMPRSS2基因表达量显著高于角膜(P=0.007),分别约为角膜上皮基因表达量的5.74倍和12.84倍。 […] 结论: 结膜中ACE2基因和TMPRSS2的表达在6种检测的眼部组织中最高,提示结膜是新型冠状病毒眼部感染的主要靶组织。
32323565 Colocalization of angiotensin-converting enzyme 2 (ACE2) and TMPRSS2 enables severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) to enter the cells.
32325025 (Cell) identify ACE2 as a SARS-CoV-2 receptor, and the latter show its entry mechanism depends on cellular serine protease TMPRSS2.
32333601 We hypothesized that the viral entry molecules angiotensin I converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) are expressed in the intestine. […] We examined the expression of Ace2 and Tmprss2 by quantitative polymerase chain reacion in animal models of IBD. […] Publicly available data from organoids and mucosal biopsies from patients with IBD were examined for expression of ACE2 and TMPRSS2. […] ACE2 and TMPRSS2 were abundantly expressed in the ileum and colon and had high expression in intestinal epithelial cells. […] Expression of ACE2 and TMPRSS2 was not increased in samples from patients with compared with those of control patients. […] In CD11b-enriched cells but not T-cells, the level of expression of ACE2 and TMPRSS2 in the mucosa was comparable to other functional mucosal genes and was not affected by inflammation. […] The viral entry molecules ACE2 and TMPRSS2 are expressed in the ileum and colon.
32343658 Transmembrane protease serine 2 (TMPRSS2) plays a role in the fusion of the virus with cells; inhibitors of this enzyme are known as well.
32345328 In this study, we investigated the gene expression of angiotensin I-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) with prognosis in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC).
32348692 Angiotensin converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) mediate viral infection of host cells. […] We reasoned that differences in ACE2 or TMPRSS2 gene expression in sputum cells among asthma patients may identify subgroups at risk for COVID19 morbidity. […] We analyzed gene expression for ACE2 and TMPRSS2, and for intercellular adhesion molecule 1 (ICAM-1)(rhinovirus receptor as a comparator), in sputum cells from 330 participants in the Severe Asthma Research Program-3 and 79 healthy controls. […] Gene expression of ACE2 was lower than TMPRSS2, and expression levels of both genes was similar in asthma and health. […] Among asthma patients, male gender, African Americans race, and history of diabetes mellitus, was associated with higher expression of ACE2 and TMPRSS2. […] Use of inhaled corticosteroids (ICS) was associated with lower expression of ACE2 and TMPRSS2, but treatment with triamcinolone acetonide (TA) did not decrease expression of either gene. […] Higher expression of ACE2 and TMPRSS2 in males, African Americans, and patients with diabetes mellitus provides rationale for monitoring these asthma subgroups for poor COVID19 outcomes. […] The lower expression of ACE2 and TMPRSS2 with ICS use warrants prospective study of ICS use as a predictor of decreased susceptibility to SARS-CoV-2 infection and decreased COVID19 morbidity.
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.
32353982 They are represented by the dynamism of the ocular surface system (e.g., the tear film turnover) and the distribution of ACE2 receptors and TMPRSS2 protein.
32354022 ACE2 can be shed by two proteases, ADAM17 and TMPRSS2. […] TMPRSS2-cleaved ACE2 allows SARS-CoV-2 cell entry, whereas ADAM17-cleaved ACE2 offers protection to organs.
32360480 Such drugs comprise inhibitors of TMPRSS2 serine protease and inhibitors of angiotensin-converting enzyme 2 (ACE2). […] Blockade of ACE2, the host cell receptor for the S protein of SARS-CoV-2 and inhibition of TMPRSS2, which is required for S protein priming may prevent cell entry of SARS-CoV-2.
32361911 Interestingly, some potential SARS-CoV-2 process-related genes such as TMPRSS2, BSG, CTSL and CTSB had different expression patterns in the same cell type.
32374427 In this study, a total of 38 conjunctival samples from 38 patients, including 12 healthy conjunctiva, 12 melanoma, 7 squamous cell carcinoma and 7 papilloma samples, were analyzed using high-throughput RNA sequencing to assess mRNA expression of the SARS-CoV-2 receptor ACE2 and its cofactors including TMPRSS2, ANPEP, DPP4, and ENPEP.
32376987 The transmembrane serine protease TMPRSS2 was previously identified as the essential protease that can cleave hemagglutinin of many subtypes of influenza virus and spike protein of coronavirus. […] Herein, we found that a guanine rich tract, capable of forming intramolecular G-quadruplex in the presence of potassium ions, in the promoter region of human TMPRSS2 gene was quite important for gene transcriptional activity, hence affecting its function. […] More importantly, compounds can down-regulate TMPRSS2 gene expression, especially endogenous TMPRSS2 protein levels, and consequently suppress influenza A virus propagation in vitro. […] Our results provide a new strategy for anti-influenza A virus infection by small molecules targeting the TMPRSS2 gene G-quadruplex and thus inhibiting TMPRSS2 expression, which is valuable for developing small molecule drugs against influenza A virus and also may be a potential candidate as anti- SARS-CoV-2 (Severe Acute Respiratory Syndrome CoV 2) lead molecules.
32379417 We show that the cell surface protein ACE2 and the protease TMPRSS2 are expressed in sustentacular cells of the olfactory epithelium but not, or much less, in most olfactory receptor neurons.
32382146 To determine the expressions of SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2) genes in human and mouse ocular cells and comparison to other tissue cells. […] The expression of ACE2 and TMPRSS2 genes was determined in human primary conjunctival and pterygium cells, human ocular and other tissue cell lines, mesenchymal stem cells as well as mouse ocular and other tissues by reverse transcription-polymerase chain reaction (RT-PCR) and SYBR green PCR. […] Expression by 2 TMPRSS2 gene primers could only be found in 1 out of 3 pterygium cell lines, but not in any conjunctival cells. […] In addition, mouse cornea had comparable expression of Tmprss2 gene and lower but prominent Ace2 gene expression compared with the lung tissue. […] Considering the necessity of both ACE2 and TMPRSS2 for SARS-CoV-2 infection, our results suggest that conjunctiva would be less likely to be infected by SARS-CoV-2, whereas pterygium possesses some possibility of SARS-CoV-2 infection. […] With high and consistent expression of Ace2 and Tmprss2 in cornea, cornea rather than conjunctiva has higher potential to be infected by SARS-CoV-2.
32387456 Cell entry of SARS-CoV-2 depends on binding of the viral spike (S) proteins to ACE2 and on S protein priming by TMPRSS2. […] Inhibition of TMPRSS2 may work to block or decrease the severity of SARS-CoV-2 infections. […] Intriguingly, TMPRSS2 is an androgen-regulated gene that is upregulated in prostate cancer where it supports tumor progression and is involved in a frequent genetic translocation with the ERG gene. […] First- or second-generation androgen-deprivation therapies (ADTs) decrease the levels of TMPRSS2.
32404436 Expression of two mucosa-specific serine proteases, TMPRSS2 and TMPRSS4, facilitated SARS-CoV-2 spike fusogenic activity and promoted virus entry into host cells.
32408547 In the current study, we used an in silico approach to screen natural compounds to find potent inhibitors of the host enzyme transmembrane protease serine 2 (TMPRSS2). […] A three-dimensional structure of TMPRSS2 was built using SWISS-MODEL and validated by RAMPAGE. […] The low-molecular-weight compound NPC306344 showed significant interaction with the active site residues of TMPRSS2, with a binding energy score of -14.69.
32410502 TMPRSS2 encodes a transmembrane serine protease which plays a crucial role in SARS-CoV-2 cell entry. […] Single nucleotide polymorphisms (SNPs) in TMPRSS2 might influence SARS-CoV2 entry into the cell. […] This study aimed to investigate the impact of SNPs on TMPRSS2 function and structure.Methods: In silico tools such as Ensembl, Gtex, ExPASY 2, GEPIA, CCLE, KEGG, and GO were engaged to characterize TMPRSS2 and it’s expression profile. […] Also, Phyre2, GOR IV, and PSIPRED were used to predict the secondary structure of TMPRSS2. […] Only 21 SNPs affected the function and structure of TMPRSS2 by influencing the protein folding, PTM, splicing, and miRNA function. […] Particularly, rs12329760 may create a de novo pocket protein. rs875393 can create a donor site, silencer and broken enhancer motifs. rs12627374 affects a wide spectrum of miRNAs profile.Conclusion: This study highlighted the role of TMPRSS2 SNPs and epigenetic mechanisms especially non-coding RNAs in appearance of different susceptibility to SARS-CoV-2 among different populations. […] Also, this study could pave the way to potential therapeutic implication of TMPRSS2 in designing antiviral drugs.
32412125 The androgen receptor regulates transcription of the transmembrane protease, serine 2 (TMPRSS2), which is required for SARS-CoV-2 infectivity. […] TMPRSS2 primes the Spike protein of the virus, which has two consequences: diminishing viral recognition by neutralizing antibodies and activating SARS-CoV-2 for virus-cell fusion.
32412310 Prostate cancer is one of the most common cancers among men and raises particular interest during the pandemic as recent reports show that the TMPRSS2 (and other serine proteases), which facilitate the entry, replication and budding of the virion from a cell, can be inhibited using androgen deprivation therapy.
32413319 SARS-CoV-2 spike (S) protein binds angiotensin-converting enzyme 2 (ACE2), and in concert with host proteases, principally transmembrane serine protease 2 (TMPRSS2), promotes cellular entry. […] We identify ACE2 and TMPRSS2 co-expressing cells within lung type II pneumocytes, ileal absorptive enterocytes, and nasal goblet secretory cells.
32422146 To extend our work in interleukin (IL)-13 biology to determine if airway epithelial cell expression of two key mediators critical for SARS-CoV-2 infection, angiotensin-converting enzyme 2 (ACE2) and transmembrane protease, serine 2 (TMPRSS2) are modulated by IL-13. […] We determined effects of IL-13 treatment on ACE2 and TMPRSS2 expression ex vivo in primary airway epithelial cells from participants with and without type 2 asthma obtained by bronchoscopy. […] We also examined expression of ACE2 and TMPRSS2 in two datasets containing gene expression data from nasal and airway epithelial cells from children and adults with asthma and allergic rhinitis. […] IL-13 significantly reduced ACE2 and increased TMPRSS2 expression ex vivo in airway epithelial cells. […] In two independent datasets, ACE2 expression was significantly reduced and TMPRSS2 was significantly increased in the nasal and airway epithelial cells in type 2 asthma and allergic rhinitis. […] ACE2 expression was significantly negatively associated with type 2 cytokines while TMPRSS2 expression was significantly positively associated with type 2 cytokines. […] IL-13 modulates ACE2 and TMPRSS2 expression in airway epithelial cells in asthma.
32423094 Firstly, SARS-CoV-2 has a strong interaction with the human ACE2 receptor, which plays an essential role in cell entry together with transmembrane serine protease 2 (TMPRSS2); it is interesting to note that the ACE2 gene lays on the X-chromosome, thus allowing females to be potentially heterozygous and differently assorted compared to men who are definitely hemizygous.
32430651 Viral entry also depends on TMPRSS2 protease activity, an androgen dependent enzyme.
32441816 Therefore, this study aimed to assess the presence of ACE2/TMPRSS2 expression in salivary glands using publicly available databases. […] The GTEx dataset was employed to explore the ACE2 and TMPRSS2 expression in various body organs and salivary glands in a healthy population. […] Transcriptome data analysis showed that ACE2 and TMPRSS2 were expressed in salivary glands. […] The expression levels of ACE2 and TMPRSS2 were marginal without significant differences in different age groups or between men and women. […] Single-cell RNA sequence analysis indicated that TMPRSS2 was mainly expressed in salivary gland epithelial cells.
32450087 We have therefore explored ACE2 receptor mRNA expression, and co-factors for Sars-CoV-2 infectivity (TMPRSS2 and furin) in bronchial brushes and biopsies from people with asthma and healthy controls, and looked for relationships between asthma severity, Th2- and IL-17 dependent gene signatures, and clinical demographics (age, sex). […] These data suggest that differences in ACE2, TMPRSS2 and furin epithelial and airway gene expression are unlikely to confer enhanced COVID-19 pneumonia risk in patients with asthma across all treatment intensities and severity.
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.
32452644 The key steps of virus life cycle have been recently clarified, highlighting the role of host type 2 angiotensin converting enzyme (ACE2) and TMPRSS2 serine protease in virus-cell binding and entry, respectively. […] Importantly, major concerns derive from the androgen-dependent tissue-expression of both TMPRSS2 and ACE2, suggesting a differential clinical course of the infection between genders.
32453494 The expression of ACE2 and TMPRSS2 in the testis and in the male genital tract allows speculations about a possible testicular involvement during the infection, possibly mediated by local and/or systemic inflammation that might allow a high viral load to overcome the haemato-testicular barrier.
32455539 We found that the receptor and transmembrane protease necessary for SARS-CoV-2 entry into host cells, ACE2 and TMPRSS2, respectively, were upregulated in smoking samples from both lung and oral epithelial tissue. […] ACE2 and TMPRSS2 upregulation were both correlated to androgen pathway enrichment and the specific upregulation of central pathway regulatory genes.
32458206 Using bromhexine at a dosage that selectively inhibits TMPRSS2 and, in so doing, inhibits TMPRSS2-specific viral entry is likely to be effective against SARS-CoV-2.
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). […] Here, we analysed genetic alteration, RNA expression, and DNA methylation of TMPRSS2 and CTSL across a wide spectrum of tumors and controls. […] TMPRSS2 was overexpressed in cervical squamous cell carcinoma and endocervical adenocarcinoma, colon adenocarcinoma, prostate adenocarcinoma (PRAD), rectum adenocarcinoma (READ), uterine corpus endometrial carcinoma and uterine carcinosarcoma, with PRAD and READ exhibiting the highest expression of all cancers.
32469279 Here, we used a homology-based structural model of transmembrane protease serine 2 (TMPRSS2), a cell surface receptor, required for entry of virus to the target host cell. […] We found that both Wi-A and Wi-N could bind and stably interact at the catalytic site of TMPRSS2. […] Wi-N showed stronger interactions with TMPRSS2 catalytic residues than Wi-A and was also able to induce changes in its allosteric site. […] Furthermore, we investigated the effect of Wi-N on TMPRSS2 expression in MCF7 cells and found remarkable downregulation of TMPRSS2 mRNA in treated cells predicting dual action of Wi-N to block SARS-CoV-2 entry into the host cells.
32482249 To describe detection of severe acute respiratory syndrome (SARS)-coronavirus 2 (CoV-2) in seminal fluid of patients recovering from coronavirus disease 2019 (COVID-19) and to describe the expression profile of angiotensin-converting enzyme 2 (ACE2) and Transmembrane Serine Protease 2 (TMPRSS2) within the testicle. […] Expression patterns of ACE2 and TMPRSS2 in the human testis are explored through previously published single-cell transcriptome datasets. […] Single-cell transcriptome analysis demonstrates sparse expression of ACE2 and TMPRSS2, with almost no overlapping gene expression. […] Angiotensin-converting enzyme 2-mediated viral entry of SARS-CoV-2 into target host cells is unlikely to occur within the human testicle based on ACE2 and TMPRSS2 expression.
32491949 Specifically, decreased expression of proteins, including angiotensin-converting enzyme 2 (ACE2) and Transmembrane Serine Protease 2 (TMPRSS2) in the airway epithelium in children may prevent viral entry.
32492203 Genetic confirmation of the hypotheses regarding gene expression and mutation pattern of target genes, including angiotensin-converting enzyme-2 (ACE2), transmembrane serine protease 2 (TMPRSS2), basigin (CD147/BSG) and paired basic amino acid cleaving enzyme (FURIN/PCSK3), as well as correlation analysis, was done in relation to lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) using in silico analysis. […] The total genetic anomaly carrying rate of target genes, including ACE2, TMPRSS2, CD147/BSG, and FURIN/PCSK3, was determined as 8.1% and 21 mutations were detected, with 7 of these mutations having pathogenic features. p.H34N on the RBD binding residues for SARS-CoV-2 was determined in our LUAD patient group. […] According to gene expression analysis results, though the TMPRSS2 level was statistically significantly decreased in the LUSC patient group compared to healthy control, the ACE2 level was determined to be high in LUAD and LUSC groups.
32496587 ACE2 and TMPRSS2 were coexpressed at the epithelial sites of the lung and skin, whereas CD147 (BSG), cyclophilins (PPIA and PPIB), CD26 (DPP4) and related molecules were expressed in both, epithelium and in immune cells.
32497257 In the attempt to understand how the virus spreads and how to pharmacologically abolish it, it was highlighted that SARS-CoV-2 infects human cells by means of angiotensin converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2) and SARS-CoV-2 main protease (Mpro ).
32501810 Hence, we searched for possible genetic components of COVID-19 severity among Italians by looking at expression levels and variants in ACE2 and TMPRSS2 genes, crucial for viral infection.Exome and SNP-array data from a large Italian cohort were used to compare the rare-variants burden and polymorphisms frequency with Europeans and East Asians. […] Moreover, we looked into gene expression databases to check for sex-unbalanced expression.While we found no significant evidence that ACE2 is associated with disease severity/sex bias, TMPRSS2 levels and genetic variants proved to be possible candidate disease modulators, prompting for rapid experimental validations on large patient cohorts.
32502616 The co-expression of ACE2 receptor and entry protease TMPRSS2 was detected in the human adult conjunctival, limbal and corneal epithelium, but not in the embryonic and fetal ocular surface up to 21 post conception weeks. […] These expression patterns were corroborated by the single cell ATAC-Seq data, which revealed a permissive chromatin in ACE2 and TMPRSS2 loci in the adult conjunctival, limbal and corneal epithelium. […] Co-expression of ACE2 and TMPRSS2 was strongly detected in the superficial limbal, corneal and conjunctival epithelium, implicating these as target entry cells for SARS-CoV-2 in the ocular surface. […] Strikingly, we also identified the key pro-inflammatory signals TNF, NFKβ and IFNG as upstream regulators of the transcriptional profile of ACE2+TMPRSS2+ cells in the superficial conjunctival epithelium, suggesting that SARS-CoV-2 may utilise inflammatory driven upregulation of ACE2 and TMPRSS2 expression to enhance infection in ocular surface. […] Together our data indicate that the human ocular surface epithelium provides an additional entry portal for SARS-CoV-2, which may exploit inflammatory driven upregulation of ACE2 and TMPRSS2 entry factors to enhance infection.
32508311 Early reports have confirmed that transmembrane serine protease 2 (TMPRSS2) and angiotensin converting enzyme 2 (ACE2) are critical targets of SARS-CoV-2 that facilitate viral entry into host cells. […] TMPRSS2 and ACE2 are expressed in multiple human tissues beyond the lung including the testes where predisposition to SARS-CoV-2 infection may exist. […] TMPRSS2 is an androgen responsive gene and its fusion represents one of the most frequent alterations in prostate cancer. […] In this review, we highlight the growing evidence in support of androgen regulation of TMPRSS2 and ACE2 and the potential clinical implications of using androgen suppression to downregulate TMPRSS2 to target SARS-CoV-2. […] We also discuss the future directions and controversies that need to be addressed in order to establish the viability of targeting TMPRSS2 and/or ACE2 through androgen signaling regulation for COVID-19 treatment, particularly its relevance in the context of prostate cancer management.
32515982 The cell entry of SARS-CoV-2 depends on two host proteins angiotensin-converting enzyme 2 (ACE2) and TMPRSS2. […] It is suggested that H2S may block SARS-CoV-2 entry into host cells by interfering with ACE2 and TMPRSS2, inhibit SARS-CoV-2 replication by attenuating virus assembly/release, and protect SARS-CoV-2-induced lung damage by suppressing immune response and inflammation development.
32528233 Likewise, TMPRSS2 protease has been shown to be crucial for viral activation thus facilitating the viral engulfment.
32529643 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.
32532094 We previously found that nafamostat mesylate, an existing drug used for disseminated intravascular coagulation (DIC), effectively blocked Middle East respiratory syndrome coronavirus (MERS-CoV) S protein-mediated cell fusion by targeting transmembrane serine protease 2 (TMPRSS2), and inhibited MERS-CoV infection of human lung epithelium-derived Calu-3 cells. […] Here we established a quantitative fusion assay dependent on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S protein, angiotensin I converting enzyme 2 (ACE2) and TMPRSS2, and found that nafamostat mesylate potently inhibited the fusion while camostat mesylate was about 10-fold less active. […] On the other hand, a significantly higher dose (EC50 around 30 mM) was required for VeroE6/TMPRSS2 cells, where the TMPRSS2-independent but cathepsin-dependent endosomal infection pathway likely predominates.
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.
32537478 It has been reported that angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) are the main cell entry proteins for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and play a critical role in causing coronavirus disease 2019 (COVID-19). […] We have found a differential expression of ACE2 and TMPRSS2 in nasal and bronchial airways relative to age and diseases status. […] Moreover, the lung airway expression of both ACE2 and TMPRSS2 was found to be significantly upregulated in smokers compared with non-smokers, and in patients with chronic obstructive pulmonary disease (COPD) compared with healthy subjects. […] No difference was observed in the blood expression levels of ACE2 and TMPRSS2 between children and adults, or in COPD or diabetic patients. […] These results suggest that the observed difference in COVID-19 severity between children and adults could, in part, be attributed to the difference in ACE2 and TMPRSS2 airways tissue expression levels.
32544566 We analyzed human post-mortem eyes as well as surgical specimens for the expression of ACE2 (the receptor for SARS-CoV-2) and TMPRSS2, a cell surface-associated protease that facilitates viral entry following binding of the viral spike protein to ACE2. […] All eye and conjunctival specimens also expressed TMPRSS2. […] Finally, Western blot analysis of protein lysates from human corneal epithelium obtained during refractive surgery confirmed expression of ACE2 and TMPRSS2.
32545271 We surveyed the co-expression of SARS-CoV-2 entry genes ACE2 and TMPRSS2 throughout the GI tract to assess potential sites of infection. […] Enterocytes from the small intestine and colonocytes showed the highest proportions of cells co-expressing ACE2 and TMPRSS2.
32545518 We found that the potent Nrf2-activating composition PB125® downregulates ACE2 and TMPRSS2 mRNA expression in human liver-derived HepG2 cells. ACE2 is a surface receptor and TMPRSS2 activates the spike protein for SARS-CoV-2 entry into host cells.
32555974 Studies carried out to date on possible SARS-CoV2 drug targets highlight glycoprotein S, Mpro (main protease or protease type 3C), and a member of the transmembrane serine protease II families (TMPRSS2). […] Thus, we point out as interesting targets for future more specific research: glycoprotein S, Mpro, and TMPRSS2.
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.
32572552 The current body of evidence indicates that SARS-CoV‑2 requires the membrane-bound angiotensin-converting enzyme 2 (ACE2) and the membrane-bound serine protease TMPRSS2 to enter cells. […] Recent studies suggest that COVID-19 patients rarely exhibit viral RNA in tear film and conjunctival smears and that, ACE2 and TMPRSS2 are only expressed in very small amounts in the conjunctiva, making conjunctival infection with SARS-CoV‑2 via these mediators unlikely.
32574109 Specifically, we review the potential clinical utility of two transmembrane serine protease 2 (TMPRSS2)-targeting protease inhibitors, nafamostat mesylate and camostat mesylate, as well as two novel potent fusion inhibitors and the repurposed Ebola drug, remdesivir, which is specific to RdRp, against human coronaviruses, including SARS-CoV-2.
32574196 Both ACE2 (an entry receptor) and TMPRSS2 (used by the virus for spike protein priming) are key proteins to SARS-CoV-2 cell entry, enabling progression to COVID-19 in humans. […] To characterize potential functional variation in savanna monkey ACE2 and TMPRSS2, we inspected recently published genomic data from 245 savanna monkeys, including 163 wild monkeys from Africa and the Caribbean and 82 captive monkeys from the Vervet Research Colony (VRC).
32574272 Host proteases, e.g., cathepsins, furin, or members of the type II transmembrane serine proteases (TTSP) family, such as Transmembrane protease serine 2 (TMPRSS2), are involved in virus entry by proteolytically activating virus ligands.
32574273 Finally, a direct effect of GL or GA to reduce virus transmission exists, which may involve reduced expression of type 2 transmembrane serine protease (TMPRSS2), which is required for virus uptake.
32579258 Using SARS-CoV-2-infected VeroE6/TMPRSS2 cells, MPA and IMD-0354, but not other anti-DENV compounds/drugs, showed significant anti-SARS-CoV-2 activity.
32582302 The SARS-CoV-2 virus responsible for the infection depends on two human genes: the human receptor angiotensin converting enzyme 2 (ACE2) for cell invasion, and the serine protease TMPRSS2 for S protein priming. […] We examined 178 quantitative phenotypes including cytokines and cardio-metabolic biomarkers, as well as usage of 58 medications in 36,339 volunteers from the Lifelines population cohort, in relation to 1,273 genetic variants located in or near ACE2 and TMPRSS2. […] For example, single nucleotide polymorphisms (SNPs) near the TMPRSS2 genes were associated with thrombocytes count (p = 1.8 × 10-5).
32583042 At the time of the research, angiotensin-converting enzyme 2 (ACE2) was clearly identified as the receptor and transmembrane serine protease 2 (TMPRSS2) as the necessary protease to enable the infection of human cells with SARS-CoV‑2. […] In the eye both ACE2 and TMPRSS2 are expressed, although sometimes very weakly and with varying degrees in different tissues. […] According to current state of knowledge the eye is not considered to be a high-risk tissue due to the low ACE2 and TMPRSS2 expression.
32586380 First, we sought to identify existing FDA approved drugs that could block coronaviruses from entering cells by binding to ACE2 or TMPRSS2 using a high-throughput AI-based binding affinity prediction platform.
32587094 Using this quantitative matrix, we elucidated 47 potential functional missense variants from genomic databases within ACE2/SLC6A19/transmembrane serine protease 2 (TMPRSS2), warranting genomic enrichment analyses in SARS-CoV-2 patients.
32589459 The spike proteins of SARS-CoV-2 interact with ACE2 or basigin/CD147 receptors, regulating human-to-human transmissions of COVID-19 together with serine protease TMPRSS2. […] ACE2 is expressed in conjunctival samples at a low level, while BSG and TMPRSS2 are expressed at intermediate levels in both conjunctiva and cornea.
32591346 To facilitate proteomic research on SARS-CoV-2, this report presents deep-scale proteomes (10,000 proteins; >130,000 peptides) of common cell line models, notably Vero E6, Calu-3, Caco-2, and ACE2-A549 that characterize their protein expression profiles including viral entry factors such as ACE2 or TMPRSS2.
32591839 We detected the expression of the ACE2 receptor but not TMPRSS2 in the model.
32592038 Entrance of SARS-CoV-2 depends on the surface (S) protein interaction with host ACE2 protein and cleavage by TMPRSS2. […] To investigate bats and pangolin as hosts in SARS-CoV-2 cross-species transmission, we perform an evolutionary analysis combining viral and host phylogenies and divergence of ACE2 and TMPRSS2 amino acid sequences between CoV hosts. […] In contrast to TMPRSS2, pangolin ACE2 amino acid sequence has low evolutionary divergence compared with humans and is more divergent from bats.
32595355 One of the important SARS-CoV-2 targets namely type 2 transmembrane serine protease (TMPRSS2) was screened with NPC’s NIH small molecule library which includes approved drugs by FDA and compounds in clinical investigation. […] Both binding energy results as well as crucial residues in ligand binding were also compared with a positive control TMPRSS2 inhibitor, Camostat mesylate. […] Based on these numerical calculations we proposed a compound (benzquercin) as strong TMPRSS2 inhibitor. […] If these results can be validated by in vitro and in vivo studies, benzquercin can be considered to be used as inhibitor of TMPRSS2 at the clinical studies.
32595360 The aim of this study was to investigate the molecular interactions between monoterpenoids and spike protein of 2019-nCoV together with the cellular proteases [transmembrane serine protease 2 (TMPRSS2), cathepsin B (CatB), and cathepsin L (CatL)].
32602823 However, WIV1 could exploit the airway protease TMPRSS2 to partially evade the IFITM3 restriction.
32620366 The aim of this brief communication is to describe the pathophysiology of this sex-discrepancy, based on the infectivity mechanism of the coronavirus including the Angiotensin-Converting Enzyme 2 (ACE2), the Type II transmembrane Serine Protease (TMPRSS2), and the androgen receptor.
32622411 Identification of cell types coexpressing the key angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) genes and proteins as well as other candidates potentially involved in SARS-CoV-2 cell entry. […] On the basis of single-cell RNA sequencing data, coexpression of ACE2 and TMPRSS2 was not detected in testicular cells, including sperm. […] A subpopulation of oocytes in nonhuman primate ovarian tissue was found to express ACE2 and TMPRSS2, but coexpression was not observed in ovarian somatic cells. […] RNA expression of TMPRSS2 in 18 samples of human cumulus cells was shown to be low or absent. […] There was general agreement between publicly available bulk RNA and protein datasets in terms of ACE2 and TMPRSS2 expression patterns in testis, ovary, endometrial, and placental cells.
32635752 The mechanism of virus entry inside the host cell depends upon the cellular proteases including cathepsins, HAT, and TMPRSS2, which splits up the spike protein and causes further penetration.
32638018 Inversely, the most important S protein cleavage protease TMPRSS2 (transmembrane protease serine protease-2) in the heart exhibits an extremely lower expression than that in the lung (adjusted P < 0.0001), which may restrict entry of SARS-CoV-2 into cardiac cells. […] Furthermore, we discovered that other S protein proteases, CTSL (cathepsin L) and FURIN (furin, paired basic amino acid cleaving enzyme), were expressed in the adult heart at a similar level to that in the lung, which may compensate for TMPRSS2, mediating cardiac involvement in COVID-19. […] Compared with the lung, ACE2 is relatively more highly expressed in the human heart, while the key S protein priming protease, TMPRSS2, is rarely expressed. […] The low percentage of ACE2+/TMPRSS2+ cells reduced heart vulnerability to SARS-CoV-2 to some degree.
32641214 Gene expression was high for TMPRSS4, CTSL, CTSB, FURIN, MX1, and BSG; medium for TMPRSS2; and low for ACE2. […] TMPRSS4 expression was positively correlated with ACE2, CTSB, CTSL, MX1, and FURIN during several cycle phases; TMPRSS2 was not statistically significantly altered across the cycle. […] Endometrial tissue is likely safe from SARS-CoV-2 cell entry based on ACE2 and TMPRSS2 expression, but susceptibility increases with age.
32641482 Interestingly, overexpression of serine protease TMPRSS2 or amphotericin treatment significantly neutralized the IFN-inducible transmembrane 3 (IFITM3) restriction of human coronavirus (CoV) entry, but did not compromise the effect of LY6E on the entry of human coronaviruses.
32645344 The spike (S) glycoprotein of betacoronavirus SARS-CoV-2 is a homotrimeric class I fusion protein that exists in a metastable conformation for cleavage by host cell proteases furin and TMPRSS2, thereby undergoing substantial structural rearrangement for ACE2 host cell receptor binding and subsequent viral entry by membrane fusion.
32660890 Additionally, an important protease involved in viral entry, TMPRSS2, is regulated by androgens.
32661206 Cellular receptor ACE2, serine protease TMPRSS2 and exopeptidase CD26 (also known as DPP4) are the three membrane bound proteins potentially implicated in SARS-CoV-2 infection. […] We hypothesised that common variants from TMPRSS2 and CD26 may play critical role in infection susceptibility of predisposed population or group of individuals. […] Coding (missense) and regulatory variants from TMPRSS2 and CD26 were studied across 26 global populations. […] However, two missense SNPs, rs12329760 (TMPRSS2) and rs1129599 (CD26), were not found to be involved physically in the said interaction. […] Four regulatory variants (rs112657409, rs11910678, rs77675406 and rs713400) from TMPRSS2 were found to influence the expression of TMPRSS2 and pathologically relevant MX1. rs13015258 a 50 UTR variant from CD26 have significant role in regulation of expression of key regulatory genes that could be involved in SARS-CoV-2 internalization.
32662421 The novel coronavirus canonically utilizes the angiotensin-converting enzyme 2 (ACE2) receptor and the serine protease TMPRSS2 for cell entry. […] Herein, building upon our previous single-cell study (Pique-Regi et al., 2019), another study, and new single-cell/nuclei RNA-sequencing data, we investigated the expression of ACE2 and TMPRSS2 throughout pregnancy in the placenta as well as in third-trimester chorioamniotic membranes. […] We report that co-transcription of ACE2 and TMPRSS2 is negligible in the placenta, thus not a likely path of vertical transmission for SARS-CoV-2.
32664879 In this study, we investigated genetic susceptibility to COVID-19 by examining DNA polymorphisms in ACE2 and TMPRSS2 (two key host factors of SARS-CoV-2) from ~ 81,000 human genomes. […] We found unique genetic susceptibility across different populations in ACE2 and TMPRSS2. […] Unique but prevalent polymorphisms (including p.Val160Met (rs12329760), an expression quantitative trait locus (eQTL)) in TMPRSS2, offer potential explanations for differential genetic susceptibility to COVID-19 as well as for risk factors, including those with cancer and the high-risk group of male patients. […] We further discussed that polymorphisms in ACE2 or TMPRSS2 could guide effective treatments (i.e., hydroxychloroquine and camostat) for COVID-19. […] This study suggested that ACE2 or TMPRSS2 DNA polymorphisms were likely associated with genetic susceptibility of COVID-19, which calls for a human genetics initiative for fighting the COVID-19 pandemic.
32664949 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.
32668165 Second, mRNA for ACE2 is elevated and mRNA for TMPRSS2, a serine protease, is decreased in CF airway epithelial cells. […] Moreover, decreased TMPRSS2 would reduce SARS-CoV-2 entry into airway epithelial cells. […] Finally, the CF lung contains high levels of serine protease inhibitors including ecotin and SERPINB1, which are predicted to reduce the ability of TMPRSS2 to facilitate SARS-CoV-2 entry into airway epithelial cells.
32672528 Transmembrane serine protease 2 (TMPRSS2) has been established as one of the host proteins that facilitate entry of coronaviruses into host cells. […] The top 3000 compounds retrieved were docked into the active sites of a homology-modelled TMPRSS2. […] Two lead compounds, ZINC64606047 and ZINC05296775, were identified having binding affinities higher than those of the reference inhibitors, favorable interactions with TMPRSS2 active site residues and good ADME and medicinal chemistry properties. […] Molecular dynamics simulation was used to assess the stability and dynamics of the interactions of these compounds with TMPRSS2. […] Analyses of the trajectory dynamics collectively established further that the lead compounds bound and interacted stably with active site residues of TMPRSS2.
32675206 SARS-CoV, the agent responsible for the 2003 SARS outbreak, utilises angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) host molecules for viral entry. […] ACE2 and TMPRSS2 have recently been implicated in SARS-CoV-2 viral infection. […] We present confirmatory evidence for the presence of TMPRSS2, CD147 and GRP78 protein in vitro in airway epithelial cells and confirm broad in situ protein expression of CD147 and GRP78 in the respiratory mucosa.Collectively, our data suggest the presence of a mechanism dynamically regulating ACE2 expression in human lung, perhaps in periods of SARS-CoV-2 infection, and also suggest that alternative receptors for SARS-CoV-2 exist to facilitate initial host cell infection.
32675312 Pandemic COVID-19 by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) infection is facilitated by the ACE2 receptor and protease TMPRSS2. […] Modestly sized case series have described clinical factors associated with COVID-19, while ACE2 and TMPRSS2 expression analyses have been described in some cell types. […] We performed an integrated study of ACE2 and TMPRSS2 gene expression across and within organ systems, by normal versus tumor, across several existing databases (The Cancer Genome Atlas, Census of Immune Single Cell Expression Atlas, The Human Cell Landscape, and more). […] Matched normal tissues generally display higher ACE2 and TMPRSS2 expression compared with cancer, with normal and tumor from digestive organs expressing the highest levels. […] TMPRSS2 was less associated with immune gene expression but was strongly associated with epithelial cell abundance. […] Single-cell sequencing analysis across nine independent studies demonstrated little to no ACE2 or TMPRSS2 expression in lymphocytes or macrophages. […] ACE2 and TMPRSS2 gene expression associated with commensal microbiota in matched normal tissues particularly from colorectal cancers, with distinct bacterial populations showing strong associations. […] We performed a large-scale integration of ACE2 and TMPRSS2 gene expression across clinical, genetic, and microbiome domains.
32679424 This is surprising, considering the recent discovery of the presence of viral receptors (ACE2 and TMPRSS2) in ocular surface tissue.
32686577 Structural analyses have elucidated hot spots in viral binding domains, mutations, and specific proteins in the host such as the receptor angiotensin-converting enzyme 2 (ACE2) and the transmembrane protease serine 2 (TMPRSS2) to be implicated in cell entry and viral infectivity.
32690544 The coronaviral entry requires the spike (S)-protein for attachment to the host cell surface, and employs human angiotensin-converting enzyme 2 (hACE2) for entry and transmembrane protease serine 2 (TMPRSS2) for S-protein priming. […] Here, we describe the single nucleotide variations (SNVs) in human ACE2 and TMPRSS2. […] We detected 349 and 551 SNVs in ACE2 and TMPRSS2, respectively, in a total of 156 513 individuals. […] Using regression analysis, the total numbers of genetic variations in ACE2 and TMPRSS2 were 1.1×103 and 1.5×103, respectively, for a population of one million people. […] The majority of SNVs in ACE2 and TMPRSS2 are rare, population-specific and deleterious, and a multitude of very rare SNVs may explain different susceptibility to SARS-CoV-2.
32691370 We demonstrate for the first time that ACE2 and the entry-facilitating transmembrane protease TMPRSS2 are expressed on very small CD133+CD34+Lin-CD45- cells in human umbilical cord blood (UCB), which can be specified into functional HSCs and EPCs.
32691890 It has been suggested that some individuals may present genetic susceptibility to SARS-CoV-2 infection, with particular research interest in variants of the ACE2 and TMPRSS2 genes, involved in viral penetration into cells, in different populations and geographic regions, although insufficient information is currently available. […] Through whole-exome sequencing, the frequency of exonic variants of the ACE2, TMPRSS2, and Furin genes was analyzed in relation to presence or absence of SARS-CoV-2 infection in a familial multiple sclerosis cohort including 120 individuals from Madrid. […] While TMPRSS2 is highly polymorphic, the variants found do not coincide with those described in other studies, with the exception of rs75603675, which may be associated with SARS-CoV-2 infection. […] Despite the limited number of patients with SARS-CoV-2 infection, some variants, especially in TMPRSS2, may be associated with COVID-19.
32696234 We scanned the literature for evidence on drugs that target the virus entry machinery into host cells and consist mainly of ACE2 and TMPRSS2, as well as other cellular molecules regulating ACE2 expression, such as ADAM-17 and calmodulin. […] They include recombinant soluble ACE2, indirect ACE2 modulators (angiotensin receptor blockers, calmodulin antagonists, selective oestrogen receptor modifiers), TMPRSS2 inhibitors (camostat mesylate, nafamostat mesylate, antiandrogens, inhaled corticosteroids) and ADAM-17 enhancers (5-fluorouracil).
32698190 Here we show that engineered expression of TMPRSS2, a cellular protease that activates SARS-CoV-2 for entry into lung cells4, renders SARS-CoV-2 infection of Vero cells insensitive to chloroquine. […] Moreover, we report that chloroquine does not block infection with SARS-CoV-2 in the TMPRSS2-expressing human lung cell line Calu-3.
32703421 Following receptor binding, transmembrane protease serine 2 (encoded by TMPRSS2) primes the S protein to allow cellular uptake. […] Therefore, individual expression of TMPRSS2 may be a crucial determinant of SARS-CoV-2 infection susceptibility. […] Here, we utilized multiple large genome databases, including the GTEx portal, SNP nexus, and Ensembl genome project, to identify gene expression profiles for TMPRSS2 and its important expression quantitative trait loci. […] Our results show that four variants (rs464397, rs469390, rs2070788 and rs383510) affect expression of TMPRSS2 in lung tissue. […] Interestingly, our data shows that TMPRSS2-upregulating variants are at higher frequencies in European and American populations than in the Asian populations, which implies that these populations might be relatively susceptible to SARS-CoV-2 infection.
32703818 In the present study, we show that S can be cleaved by the proprotein convertase furin at the S1/S2 site and the transmembrane serine protease 2 (TMPRSS2) at the S2’ site. […] We demonstrate that TMPRSS2 is essential for activation of SARS-CoV-2 S in Calu-3 human airway epithelial cells through antisense-mediated knockdown of TMPRSS2 expression. […] Combining various TMPRSS2 inhibitors with furin inhibitor MI-1851 produced more potent antiviral activity against SARS-CoV-2 than an equimolar amount of any single serine protease inhibitor.
32709978 Delving into the possible mechanisms underlying the crosstalk between COVID-19 and PCa alludes a potential association between SARS-CoV-2 targets on host epithelial cells and PCa genetic aberrations and molecular signatures, including AR and TMPRSS2.
32721806 Angiotensin-converting enzyme-2 (ACE2) receptor, regulation of the renin-angiotensin-aldosterone system (RAAS), and transmembrane serine protease 2 (TMPRSS2) action are critical for the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) cell entry and infectivity. […] ACE2 expression and RAAS are abnormal in hypertension and obesity, while TMPRSS2 is overexpressed when exposed to androgens, which may justify why these factors are overrepresented in COVID-19. […] Current data shows that spironolactone may concurrently mitigate abnormal ACE2 expression, correct the balances membrane-attached and free circulating ACE2 and between angiotensin II and Angiotensin-(1-7) (Ang-(1-7)), suppress androgen-mediated TMPRSS2 activity, and inhibit obesity-related RAAS dysfunctions, with consequent decrease of viral priming.
32726128 Testosterone on the contrary enhances the levels of the two most critical molecules, angiotensin-converting enzyme 2 (ACE2) and the transmembrane protease serine-type 2 (TMPRSS2), transcriptionally and posttranslationally, thereby increasing viral load and delaying viral clearance in men as compared with women.
32726325 Development of novel approaches for regulating the expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) is becoming increasingly important within the context of the ongoing COVID-19 pandemic since these enzymes play a crucial role in cell infection. […] In this work we searched for putative ACE2 and TMPRSS2 expression regulation networks mediated by various miRNA isoforms (isomiR) across different human organs using publicly available paired miRNA/mRNA-sequencing data from The Cancer Genome Atlas (TCGA) project. […] As a result, we identified several miRNA families targeting ACE2 and TMPRSS2 genes in multiple tissues. […] In particular, we found that lysine-specific demethylase 5B (JARID1B), encoded by the KDM5B gene, can indirectly affect ACE2 / TMPRSS2 expression by repressing transcription of hsa-let-7e / hsa-mir-125a and hsa-mir-141 / hsa-miR-200 miRNA families which are targeting these genes.
32730512 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.
32730844 A putative target to interfere with the virus is the host transmembrane serine protease family member II (TMPRSS2). […] Repositioning approved, investigational and experimental drugs on the serine protease domain of TMPRSS2 could thus be valuable. […] There is no experimental structure for TMPRSS2 but it is possible to develop quality structural models for the serine protease domain using comparative modeling strategies as such domains are highly structurally conserved. […] Beside the TMPRSS2 catalytic site, we predicted on our structural models a main exosite that could be important for the binding of protein partners and/or substrates. […] To block the catalytic site or the exosite of TMPRSS2 we used structure-based virtual screening computations and two different collections of approved, investigational and experimental drugs. […] These small molecules should now be tested in vitro to gain novel insights over the roles of TMPRSS2 or as starting point for the development of second generation analogs.
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.
32734518 As a result, the COVID-19 lifecycle were categorized as following steps: “Host Cell Attachment” which is mainly conducted with ACE2 receptors and TMPRSS2 from the host cell and Spike (S) protein, “Endocytosis Pathway” which is performed mainly by clathrin-mediated endocytosis, and “Viral Replication” which contains translation and replication of RNA viral genome.
32741259 SARS-CoV and SARS-CoV-2 employ the host cellular serine protease TMPRSS2 for spike (S) protein priming for viral entry into host cells. […] A potential way to reduce the initial site of SARS-CoV-2 infection may be to inhibit the activity of TMPRSS2. […] In the current study, the three-dimensional structure of TMPRSS2 was generated by homology modelling and subsequently validated with a number of parameters. […] The structure-based virtual screening of Selleckchem database was performed through ‘Virtual Work Flow’ (VSW) to find out potential lead-like TMPRSS2 inhibitors. […] Camostat and bromhexine are known TMPRSS2 inhibitor drugs, hence these were used as control molecules throughout the study. […] Based on better dock score, binding-free energy and binding interactions compared to the control molecules, six molecules (Neohesperidin, Myricitrin, Quercitrin, Naringin, Icariin, and Ambroxol) were found to be promising against the TMPRSS2. […] Binding interactions analysis revealed a number of significant binding interactions with binding site amino residues of TMPRSS2. […] The binding energy calculated from the MD simulation trajectories also favour the strong affinity of the molecules towards the TMPRSS2.
32741970 None have shown placental expression of the ACE2 or TMPRSS2 protein, both required for viral infection. […] We examined 19 COVID-19 exposed placentas for histopathologic findings, and for expression of ACE2, and TMPRSS2 by immunohistochemistry. […] TMPRSS2 expression was only present weakly in the villous endothelium and rarely in the ST. […] We propose one explanation could be the polarized expression of ACE2 away from the maternal blood and pronounced paucity of TMPRSS2 expression in trophoblast.
32744436 Our study provided the cellular evidence that SARS-Cov-2 invaded human kidney tissue via proximal convoluted tubule, proximal tubule, proximal straight tubule cells, and glomerular parietal cells by means of ACE2-related pathway and used their cellular protease TMPRSS2 for priming.
32748331 It has been reported that SARS-CoV-2 enters into the host cell through interaction between conserved residues of viral spike protein and angiotensin converting enzyme 2 (ACE2) receptor which is highly expressed in host’s cardiac and pulmonary cells and finally transmembrane protease, serine-2 (TMPRSS2), helps in priming of the surface protein.
32750256 Here, we examine human pre-gastrulation embryos to determine the expression patterns of the genes ACE2, encoding the SARS-CoV-2 receptor, and TMPRSS2, encoding a protease that cleaves both the viral spike protein and the ACE2 receptor to facilitate infection. […] Expression of ACE2 and TMPRSS2 in these tissues raises the possibility for vertical transmission and indicates that further work is required to understand potential risks to implantation, placental health and fetal health that require further study.
32755524 SARS-CoV-2, which is an enveloped, RNA virus has been shown to attach to the host cell receptor angiotensin converting enzyme 2 with spike (S) protein and membrane fusion is provided by transmembrane protease serine 2 (TMPRSS2) of the host cell.
32757420 We therefore performed data mining of two independent NCBI GEO genome-wide RNA expression files (GSE7894 and GSE994) and report that in both data sets, current smokers and never smokers have, on average, closely similar bronchial epithelial cell mRNA levels of ACE2, as well as TMPRSS2, coding for a serine protease priming SARS-Cov-2 for cell entry, and ADAM17, coding for a protease implicated in ACE2 membrane shedding. […] In contrast, the expression levels of TMPRSS4, coding for a protease that primes SARS-CoV-2 for cell entry similarly to TMPRSS2, were elevated in bronchial epithelial cells from current smokers compared with never smokers, suggesting that higher bronchial TMPRSS4 levels in smokers might put them at higher SARS-Cov-2 infection risk.
32758873 These viral calcium-dependent binding domains can facilitate membrane fusion only after cleavage by the host surface protease TMPRSS2. […] Importantly, TMPRSS2 also requires calcium for its SRCR (scavenger receptor cysteine-rich) domain and itsLDLRA(LDL receptor class A) domain.
32759995 The entry of SARS-CoV-2 into host cells is dependent upon angiotensin-converting enzyme 2 (ACE2), which serves as a functional attachment receptor for the viral spike glycoprotein, and the serine protease TMPRSS2 which allows fusion of the viral and host cell membranes. […] We devised a quantitative measure to estimate genetic determinants of ACE2 and TMPRSS2 expression and applied this measure to >2500 individuals. […] Our data show significant variability in genetic determinants of ACE2 and TMPRSS2 expression among individuals and between populations, and indicate a genetic predisposition for lower expression levels of both key viral entry genes in African populations.
32764200 Among 126 potential convalescent plasma donors, the humoral immune response was evaluated using a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus neutralization assay with Vero-E6-TMPRSS2 cells; a commercial IgG and IgA ELISA to detect the spike (S) protein S1 domain (EUROIMMUN); IgA, IgG, and IgM indirect ELISAs to detect the full-length S protein or S receptor-binding domain (S-RBD); and an IgG avidity assay.
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.
32768580 This study investigates the N720D variant, positioned in the collectrin-like domain (CLD) at proximity to type II transmembrane serine protease (TMPRSS2) cleavage site. […] HDOCK was utilised to model TMPRSS2 protease binding to ACE2 WT and D720 variant cleavage site. […] PRODIGY was used to calculate binding affinities and MD simulation tools calculated the at 100 ns for ACE2 apo structure and the ACE2-TMPRSS2 complex. […] As such, introducing a tighter binding affinity of Kd = 3.2 × 10-10 M between TMPRSS2 and N720D variant. […] RMSD, RMSF calculations showed the N720D variant is less stable, however, RMSF values of the D720-TMPRSS2 complex reflected a slower dynamic motion. […] The hotspot N720D variant in the CLD of ACE2 affected the stability and flexibility of ACE2 by increasing the level of motion in the loop region, resulting in a more favourable site for TMPRSS2 binding and cleavage. […] Consequently, this would facilitate S-protein binding and can potentially increase viral entry highlighting the importance of variants affecting the ACE2-TMPRSS2 complex.
32774170 The sex-prevalent expression of the attachment and permissive molecules ACE2 and TMPRSS2 further supports the concept of a male-oriented vulnerability.
32779305 Docking analysis identified lead molecules with favorable binding energy, number of poses and hydrogen bond interactions, which indicates the effective modulation of ACE2 and TMPRSS2 receptors.
32783758 It illustrates new analyses of the structure of ACE2 that provides better understanding of its actions particularly in lung and gut, shedding of ACE2 by ADAM17 (a disintegrin and metallopeptidase domain 17 protein), and role of TMPRSS2 (transmembrane serine proteases 2) in severe acute respiratory syndrome coronavirus-2 entry into host cells.
32784802 The entry process involves priming of the S protein by TMPRSS2 and ADAM17, which collectively mediate the binding and promote ACE2 shedding. […] In this study, microarray and RNA-sequencing (RNA-seq) expression data were utilized to profile the expression pattern of ACE2, ADAM17, and TMPRSS2 in type 2 diabetic (T2D) and non-diabetic human pancreatic islets. […] Islets from female donors showed higher ACE2 expression compared to males; the expression of ADAM17 and TMPRSS2 was not affected by gender. […] Obese (BMI > 30) donors have significantly higher expression levels of ADAM17 and TMPRSS2 relative to those from non-obese donors (BMI < 25). […] TMPRSS2 expression correlated positively with HbA1c and negatively with age, while ADAM17 and TMPRSS2 correlated positively with BMI.
32784899 The inhibition of host TMPRSS2 and cathepsins B/L may represent a complementary strategy to be investigated. […] In this review, we discuss the development entry inhibitors targeting the S protein, as well as the most promising host targeting strategies involving TMPRSS2 and CatB/L, which have been exploited so far against CoVs and other related viruses.
32788194 Stable introduction of the Spike-activating protease TMPRSS2 further enhanced susceptibility to infection by 5- to 10-fold.
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. […] The expression level of TMPRSS2 was increased with a number of medications, such as diclofenac, furosemide, and dexamethasone, whereas other medications, such as allopurinol, suppressed the expression of this gene. […] 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.
32808185 Angiotensin-converting enzyme 2 (ACE2) and Transmembrane serine protease (TMPRSS2) are the main cell entry receptors of SARS-CoV-2. […] The expression level of TMPRSS2 was increased noticeably with a number of medications such as metformin. […] To confirm the observed effects on primary human hepatocytes, rat hepatocyte treatments data was obtained from DrugMatrix toxicogenomic database (GSE57805), which showed a similar ACE2 and TMPRSS2 expression pattern. […] Treatment of common co-morbidities often require chronic use of multiple medications, which may result in an additive increase in the expression of ACE2 and TMPRSS2.
32810867 Recent research has confirmed the role of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) as key host-specific cellular moieties responsible for the cellular entry of the virus. […] Accordingly, the ongoing medical examinations and the autopsy reports of the deceased individuals indicate that organs/tissues with high expression levels of ACE2, TMPRSS2 and other putative viral entry-associated genes are most vulnerable to the infection. […] Co-expression analysis of ACE2 and TMPRSS2 and protein-protein interaction among the host and viral proteins elected regulatory cytoskeleton protein-enriched SUSs as the most vulnerable cell type of the olfactory epithelium.
32816230 To review the data regarding the expression of angiotensin converting enzyme-2 (ACE2) and transmembrane protease serine-2 (TMPRSS2) in head and neck tissue. […] Scopus, Cochrane Library, Medrxiv, Google Scholar and PubMED/MEDLINE were searched by four independent investigators for studies investigating ACE2 or TMPRSS2 expressions in head and neck tissues. […] ACE2 and TMPRSS2 were expressed in oral, pharyngeal, sinusonasal human mucosa. […] TMPRSS2 was found in goblet and apical respiratory cells. […] ACE2 and TMPRSS2 were found in the olfactory region, especially in sustentacular non-neural and neural stem cells. […] There was an important heterogeneity between studies in the methods used to detect ACE2 and TMPRSS2, leading to a potential identification bias. […] The SARS-CoV-2 receptors, ACE2 and TMPRSS2, are both expressed in many head and neck tissues, enabling the viral entry into the host organism.
32820005 Here, we show that two indole-chloropyridinyl-ester derivatives, GRL-0820 and GRL-0920, exerted potent activity against SARS-CoV-2 in cell-based assays performed using VeroE6 cells and TMPRSS2-overexpressing VeroE6 cells.
32824674 High testosterone levels could upregulate transmembrane serine protease 2 (TMPRSS2), facilitating the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into host cells via angiotensin-converting enzyme 2 (ACE2). […] Clinical studies on TMPRSS2 inhibitors, such as camostat, nafamostat, and bromhexine, are ongoing.
32825469 The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor, angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), and furin, which promote entry of the virus into the host cell, have been identified as determinants of SARS-CoV-2 infection. […] TMPRSS2 was strongly expressed in stratified squamous epithelium in the keratinized surface layer and detected in the saliva and tongue coating samples via Western blot. […] ACE2, TMPRSS2, and furin mRNA expression was observed in taste bud-derived cultured cells, which was similar to the immunofluorescence observations.
32826650 Using immunohistochemistry, the samples were tested for the expression of angiotension-converting enzyme 2 (ACE2), dendritic cell-specific intracellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN), DC-SIGN-related protein (DC-SIGNR), and transmembrane serine protease 2 (TMPRSS2). […] In all specimens, both ACE2 and TMPRSS2 were expressed throughout the surface epithelium (corneal, limbal, and conjunctival) and corneal endothelium. […] In corneal stromal cells, ACE2 was sporadically expressed, whereas TMPRSS2 was absent. […] ACE2, TMPRSS2, and DC-SIGN/DC-SIGNR were all expressed in the cultured corneal, limbal, and conjunctival epithelial cells. […] Both corneal and conjunctival epithelia express ACE2, DC-SIGN/DC-SIGNR, and TMPRSS2, suggesting that the ocular surface is a potential route for the transmission of SARS-CoV-2.
32829149 This paper focuses on the human protein TMPRSS2, which supports coronavirus life cycles by cleaving viral spike proteins. […] The three-dimensional structure of TMPRSS2 is not known and so we have generated models of the TMPRSS2 in the apo state as well as in complex with a peptide substrate and putative inhibitors to aid future work. […] Importantly, many related human proteases have 80% or higher identity with TMPRSS2 in the S1-S1’ subsites, with plasminogen and urokinase-type plasminogen activator (uPA) having 95% identity. […] We highlight 376 approved, investigational or experimental drugs targeting S1A serine proteases that may also inhibit TMPRSS2. […] Whilst the presence of a relatively uncommon lysine residue in the S2/S3 subsites means that some serine protease inhibitors will not inhibit TMPRSS2, this residue is likely to provide a handle for selective targeting in a focused drug discovery project. […] We discuss how experimental drugs targeting related serine proteases might be repurposed as TMPRSS2 inhibitors to treat coronaviruses.
32831324 To determine the susceptibility of the skin to SARS-CoV-2 infection based on the expression of viral entry factors ACE2 and TMPRSS2 in this organ. […] A comprehensive analysis of human tissue gene expression databases was carried out looking for the presence of the ACE2 and TMPRSS2 genes in the skin. mRNA expression of these genes in skin-derived human cell lines was also assessed. […] The analyses showed high co-expression of ACE2 and TMPRSS2 in the gastrointestinal tract and kidney, but not in the skin. […] Only the human immortalized keratinocyte HaCaT cell line expressed detectable levels of ACE2, and no cell line originating in the skin expressed TMPRSS2.
32831326 ACE2, CD147 and TMPRSS2 receptors expression could indicate poorly explored potential infection targets.
32835083 Third, nearly 1033 medicinal herbal compounds were collected and docked with ACE2, TMPRSS2, GRP78, and AT1R receptors, which were the most noticeable receptors in causing the COVID-19.
32835700 The allelic frequencies of the polymorphisms in the ACE2, TMPRSS2, TMPRSS11A, cathepsin L (CTSL), and elastase (ELANE) genes were obtained in four populations from the American, African, European, and Asian continents reported in the 1000 Genome Project. […] In the coding sequences of these genes, we detected one probably-damaging polymorphism located in the TMPRSS2 gene (rs12329760) that produces a change of amino acid. […] Furthermore, forty-eight polymorphisms with possible functional consequences were detected in the non-coding sequences of the following genes: three in ACE2, seventeen in TMPRSS2, ten in TMPRSS11A, twelve in ELANE, and six in CTSL.
32837754 In order to investigate the potential risk of SARS-CoV-2 vertical transmission, we explored ACE2 and transmembrane protease serine 2 (TMPRSS2) expression patterns in peri-implantation embryos and the maternal-fetal interface using previously published single-cell transcriptome data. […] The results show that day 6 (D6) trophectoderm cells (TE) in peri-implantation embryos, as well as syncytiotrophoblast (STB) at 8 weeks of gestation (STB_8W) and extravillous trophoblasts cells (EVT) at 24 weeks of gestation (EVT_24W) in the maternal-fetal interface, strongly co-expressed ACE2 and TMPRSS2, indicating SARS-CoV-2 infection susceptibility.
32837954 Virtual screening was then performed for the 18 selected drugs with ACE2, 3CLpro and PLpro and HR1 and TMPRSS2.
32842606 Recent studies have shown that two human proteases, TMPRSS2 and cathepsin L, play a key role in host cell entry of SARS-CoV-2. […] Here, we perform virtual screening of 14,011 phytochemicals produced by Indian medicinal plants to identify natural product inhibitors of TMPRSS2 and cathepsin L. […] AutoDock Vina was used to perform molecular docking of phytochemicals against TMPRSS2 and cathepsin L. […] Potential phytochemical inhibitors were filtered by comparing their docked binding energies with those of known inhibitors of TMPRSS2 and cathepsin L. […] This led to the identification of 96 inhibitors of TMPRSS2 and 9 inhibitors of cathepsin L among phytochemicals of Indian medicinal plants. […] Further, we have performed molecular dynamics (MD) simulations to analyze the stability of the protein-ligand complexes for the three top inhibitors of TMPRSS2 namely, qingdainone, edgeworoside C and adlumidine, and of cathepsin L namely, ararobinol, (+)-oxoturkiyenine and 3α,17α-cinchophylline.
32844538 A1AT inhibits SARS-CoV-2 infection and two of the most important proteases in the pathophysiology of Covid-19: the transmembrane serine protease 2 (TMPRSS2) and the disintegrin and metalloproteinase 17 (ADAM17). […] TMPRSS2 is essential for SARS-CoV-2-S protein priming and viral infection. […] In this review, we focused on the interplay between A1AT with TMPRSS2, ADAM17 and immune molecules, and the role of A1AT in the pathophysiology of Covid-19, opening new avenues for investigating effective treatments.
32848776 In this proposed pathway, membrane fusion and cytoplasmic entry of SARS-CoV-2 virus via ACE2 and TMPRSS2-expressing respiratory epithelial cells, including pulmonary type-II pneumocytes, provoke an initial immune response featuring inflammatory cytokine production coupled with a weak interferon response, particularly in IFN-λ-dependent epithelial defense.
32851697 Via bioinformatic analysis, we identified the existence of ACE2 and TMPRSS2 expression in human TE as well as in the first- and second- trimester placentas. […] As for TMPRSS2, 90.7% of TE1 cells, 31.5% of CTBs, 22.1% of EVTs and 70.8% of STBs were TMPRSS2 positive. […] And 1.6% of CTBs, 26.5% of STBs, 1.9% of EVT_8W and 20.1% of EVT_24W were TMPRSS2 positive. […] Pathway analysis revealed associations to morphogenesis of branching structure, extracellular matrix interaction, oxygen binding and antioxidant activity in ACE2+TMPRSS2+ EVT_24W cells. […] The ACE2+TMPRSS2+ TE1 cells were correlated with an increased capacity of viral invasion, epithelial cell proliferation and cell adhesion. […] Based on immunohistochemical results, expression level of ACE2 and TMPRSS2 in first- and second- and third-trimester placentas was observed. […] Our study has demonstrated the presence of ACE2 and TMPRSS2 positive cells in the human TE and placentas at different stages of pregnancy, which indicates the possibility that the SARS-CoV-2 could spread via the placenta and cause intrauterine fetal infection.
32851855 ACE2 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).
32857620 TMPRSS2, ACE2 and TMPRSS11D are genes coding for proteins necessary for SARS-CoV-2 activation, infection and transmission. […] Cell cultures treated with 10µg of azithromycin significantly downregulated receptor-mediated endocytosis canonical pathways involving TMPRSS2 and TMPRSS11D genes. […] This proof of concept demonstrates azithromycin downregulates pathways involving serine proteases TMPRSS2 and TMPRSS11D required for SARS-CoV-2 activation and its cell-to-cell transmission while downregulating pro-inflammatory cytokine IL-1β, NDST-1 and their associated pathways.
32858233 Here we investigated whether genetic variation in the key genes for viral entry to host cells-ACE2 and TMPRSS2-and sensing of viral genomic RNAs (i.e., TLR3/7/8) could explain the variation in incidence across diverse ethnic groups.
32861070 And transmembrane protease serine 2 (TMPRSS2) could cleave the spike (S) protein of SARS-CoV-2, which facilitates the fusion of SARS-CoV-2 and cellular membranes. […] The mRNA expressions of both ACE2 and TMPRSS2 were observed in the heart, digestive tract, liver, kidney, brain and other organs. […] SARS-CoV-2 may have a capacity to infect extrapulmonary organs due to the expressions of ACE2 and TMPRSS2 in the cells and tissues of these organs. […] It seems that there is a potential involvement of ACE2 and TMPRSS2 expressions in the virus infection of extrapulmonary organs and the manifestation of symptoms related to these organs in patients with COVID-19. […] Here, we revealed the expressions of ACE2 and TMPRSS2 in extrapulmonary organs, and we also summarized the clinical manifestation and the management of extrapulmonary complications in patients with COVID-19.
32861340 Transmembrane protease serine 2 (TMPRSS2), which interacts with ACE2, may be a better candidate for targeted therapies. […] Using publicly available expression data, we show that both ACE2 and TMPRSS2 are expressed in many host tissues, including lung. […] The highest expression of ACE2 is found in the testes, whereas the prostate displays the highest expression of TMPRSS2. […] Given the increased severity of disease among older men with SARS-CoV-2 infection, we address the potential roles of ACE2 and TMPRSS2 in their contribution to the sex differences in severity of disease. […] We show that expression levels of ACE2 and TMPRSS2 are overall comparable between men and women in multiple tissues, suggesting that differences in the expression levels of TMPRSS2 and ACE2 in the lung and other non-sex-specific tissues may not explain the gender disparities in severity of SARS CoV-2. […] However, given their instrumental roles for SARS-CoV-2 infection and their pleiotropic expression, targeting the activity and expression levels of TMPRSS2 is a rational approach to treat COVID-19.
32862058 Using comparative immunofluorescence, we examined the localization and relative tissue abundance of SARS-CoV2 spike glycoprotein (CoV2 SP) along with the co-localization of two SARS-CoV2 viral entry proteins angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). […] We further identified the predominance of ACE2 expression in comparison with TMPRSS2.
32863223 SARS-CoV-2 infects human cells by binding to the cellular surface protein angiotensin-converting enzyme 2 (ACE2); in addition, the cellular transmembrane serine protease 2 (TMPRSS2) is needed for priming of the spike (S) protein of the virus. […] Herein, we performed an expression profiling meta-analysis of ACE2, TMPRSS2 and CTSB/L genes (and proteins) in public repository databases and found that all are widely expressed in human tissues; also, the ACE2 and TMPRSS2 genes tend to be co-regulated. […] Finally, we analyzed KEGG pathways modulated by ACE2, TMPRSS2 and CTSB/L and probed DrugBank for drugs that target modules of the affected pathways.
32864545 Androgens upregulate the protease TMPRSS2 (type II transmembrane serine protease-2), which facilitates efficient virus-host cell fusion with the epithelium of the lungs, thus increasing susceptibility to SARS-CoV-2 infection and development of severe COVID-19. […] Owing to low levels of steroid hormones, prepubertal children may have low expression of TMPRSS2, thereby limiting the viral entry into host cells.
32866534 Angiotensin-converting enzyme 2 (ACE2) receptor serves as an entry point for this deadly virus while the proteases like furin, transmembrane protease serine 2 (TMPRSS2) and 3 chymotrypsin-like protease (3CLpro) are involved in the further processing and replication of SARS-CoV-2. […] The representative compounds A_BR4, A_BR9, A_BR18, A_BR22 and A_BR28 restricted the interaction of SARS-CoV-2 SP with ACE2 and host proteases furin and TMPRSS2.
32867305 We analyzed 131 COVID-19 patients by exome sequencing and examined the genetic variants of TMPRSS2, PCSK3, DPP4, and BSG genes. […] In TMPRSS2 gene, we observed a significant difference in the frequency of c.331G>A, c.23G>T, and c.589G>A variant alleles in COVID-19 patients, compared to the corresponding allelic frequency in GnomAD.
32868983 Based on the “steric-clashes alleviating receptor (SCAR)” strategy developed in our lab recently, we screened the library of clinic and investigational drugs, and identified nine drugs that might be repurposed as covalent inhibitors of the priming proteases (cathepsin B, cathepsin L, and TMPRSS2) of the spike protein of SARS-CoV-2.
32873611 The above findings also largely apply to the SARS-CoV-2 entry protease TMPRSS2.
32873700 Transmembrane serine protease 2 is encoded by the TMPRSS2 gene. […] A fusion gene between the TMPRSS2 gene and ERG (erythroblast-specific-related gene), an oncogenic transcription factor, is the most common chromosomal aberration detected in prostate cancer, responsible for driving carcinogenesis. […] The other key role of TMPRSS2 is in priming the viral spike protein which facilitates viral entry essential for viral infectivity. […] Both SARS-CoV and SARS-CoV-2 (COVID-19) use angiotensin-converting enzyme 2 (ACE2) and TMPRSS2 to facilitate entry to cells, but with SARS-CoV-2 human-to-human transmission is much higher than SARS-CoV. […] As TMPRSS2 is expressed outside of the lung, and can therefore contribute to extrapulmonary spread of viruses, it warrants further exploration as a potential target for limiting viral spread and infectivity.
32878480 To date, no study has examined whether an increased fraction of inspired oxygen (FiO2) may affect the expression of SARS-CoV-2 entry receptors and co-receptors, including ACE2 and the transmembrane serine proteases TMPRSS1, TMPRSS2, and TMPRSS11D.
32883010 The ocular surface and retina have the necessary proteins, Transmembrane Serine Protease 2 (TMPRSS2), CD147, Angiotensin-Converting Enzyme 2 (ACE2) and Cathepsin L (CTSL) necessary to be infected with SARS-CoV-2.
32887532 The current emphasis is primarily on TMPRSS2, matriptase, and hepsin, yet other TTSPs await validation.
32887634 Platelets expressed ACE2, a host cell receptor for SARS-CoV-2, and TMPRSS2, a serine protease for Spike protein priming.
32890967 SARS-CoV-2 entry into host cells is characterized by viral spike protein interaction with cellular angiotensin-converting enzyme 2 (ACE2) and serine protease TMPRSS2. […] Propolis components have inhibitory effects on the ACE2, TMPRSS2 and PAK1 signaling pathways; in addition, antiviral activity has been proven in vitro and in vivo.
32897764 TMPRSS2 is a host co-receptor for cell entry of SARS-CoV-2. […] One prior report suggested that use of androgen deprivation therapy (ADT), which downregulates TMPRSS2, may protect men with prostate cancer from infection.
32903321 The new coronavirus (SARS-CoV-2), which has been responsible for the recent coronavirus disease 2019 (COVID-19) pandemic, uses the cell receptor angiotensin converting enzyme-2 (ACE2) for entry and the serine protease TMPRSS2 for spike (S) protein priming. […] Meanwhile, the presence of B0AT1 (SLC6A19) may prevent TMPRSS2 from accessing the cutting position on ACE2. […] The single-cell transcription datasets of the human cell landscape (HCL) and other relevant single-cell transcription databases were used to analyze the expression of ACE2, TMPRSS2, and SLC6A19 in various organs and tissues, but mainly in the kidney. […] TMPRSS2 was widely expressed in several renal tubule populations extending from the PT cells to the collection system cell type, of which intercalated cells and the distal convoluted tubule cells showed more significant expression than PT cells. […] Although alveolar-type (AT) 2 cells of the lung and intestinal epithelial cells expressed ACE2 as well as PT cells, AT 2 cells significantly expressed TMPRSS2 but not SLC6A19, while all 3 genes were significantly expressed in intestinal epithelial cells.
32905655 During infection, SARS-CoV-2 via its binding target ACE2 and TMPRSS2 can disrupt mitochondrial function.
32914167 We found that targeting FURIN and TMPRSS2 can provide good results due to their common involvement in current and previous outbreaks.
32918944 Transmembrane protease serine 2 (TMPRSS2) has been shown to prime the viral spike for its interaction with its receptor. […] In this study, we used several bioinformatics approaches to bring clues in the interaction of ACE2, TMPRSS2, and GRP78 with SARS-CoV-2. […] On the other hand, TMPRSS2 and GRP78 are proteins with high homology in all the evaluated hosts.
32924827 The results indicated that, Ritonavir has the highest potency to block SARS-CoV-2 main protease and human TMPRSS2, a host cell factor that aids viral infection.
32930394 Immunohistochemistry for the receptor of the SARS-COV 2, ACE2, and its priming activatorTMPRSS2 revealed that both proteins co-localize in airway cells. […] Pneumocytes but not endothelial cells also expressed TMPRSS2.
32936429 A tentative hypothesis to explain these findings is the role of angiotensin-converting enzyme 2 (ACE2) and serine protease TMPRSS2 involved in viral infection. […] In this review, we summarize the available evidence pointing to gender-related differences in ACE2 and TMPRSS2 expression, from both genetic and endocrine points of view. […] Altogether, available evidence points toward two not-mutually exclusive mechanisms in gender susceptibility to COVID-19 by sex hormonal regulation of ACE2 and TMPRSS2. […] On the other, low levels of androgens in women may keep at low levels TMPRSS2 expression, representing a further protective factor for the development of COVID-19 infection, despite the increased expression of ACE2, which represents the Trojan horse for SARS-CoV-2 entry.
32936531 The SARS-CoV-2 makes its way into the cell via the ACE2 receptor and the proteolytic action of TMPRSS2.
32937591 Bulk sequencing demonstrated that mouse, non-human primate and human olfactory mucosa expresses two key genes involved in CoV-2 entry, ACE2 and TMPRSS2.
32940922 Cellular entry of SARS-CoV-2 depends on the binding of its spike protein to a cellular receptor named angiotensin-converting enzyme 2 (ACE2), and the subsequent spike protein-priming by host cell proteases, including transmembrane protease serine 2 (TMPRSS2). […] Thus, high expression of ACE2 and TMPRSS2 is considered to enhance the invading capacity of SARS-CoV-2. […] To elucidate the underlying histological mechanisms of the aerodigestive disorders caused by SARS-CoV-2, we investigated the expression of ACE2 and TMPRSS2 proteins using immunohistochemistry, in the aerodigestive tracts of the tongue, hard palate with partial nasal tissue, larynx with hypopharynx, trachea, esophagus, and lung of rats. […] Co-expression of ACE2 and TMPRSS2 proteins was observed in the taste buds of the tongue, nasal epithelium, trachea, bronchioles, and alveoli with varying degrees of expression. […] Remarkably, TMPRSS2 expression was more distinct in the peripheral alveoli than in the central alveoli. […] A wide range of organs have been speculated to be affected by SARS-CoV-2 depending on the expression levels of ACE2 and TMPRSS2. […] Differential distribution of TMPRSS2 in the lung indicated the COVID-19 symptoms to possibly be exacerbated by TMPRSS2 expression.
32944935 Reports denote SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2) as its primary entry point into the host cell. […] Here, we used single-cell RNA sequencing data of human organoids to analyze expressions of ACE2 and TMPRSS2, in addition to an array of RNA receptors to examine their role in SARS-CoV-2 pathogenesis. […] ACE2 is abundant in all organoids, except the prostate and brain, and TMPRSS2 is omnipresent.
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.
32960480 The plasma serine protease inhibitor alpha-1 antitrypsin was suggested to protect from COVID-19 by inhibiting TMPRSS2, a cell surface serine protease essential for the SARS-CoV-2 cell entry.
32967703 SARS-coronavirus-2 enters host cells through binding of the Spike protein to ACE2 receptor and subsequent S priming by the TMPRSS2 protease. […] We aim to assess differences in both ACE2 and TMPRSS2 expression in normal tissues from oral cavity, pharynx, larynx and lung tissues as well as neoplastic tissues from the same areas. […] TMPRSS2 expression in HNSCC was significantly reduced compared to the normal tissues. […] Functionally, we modeled the multivariate effect of TP53, HPV, and other inherent variables on TMPRSS2. […] All variables had a statistically significant independent effect on TMPRSS2. […] In particular, in tumor tissues, HPV negative, TP53 mutated status and elevated TP53-dependent Myc-target genes were associated with low TMPRSS2 expression. […] The further analysis of both TCGA and our institutional HNSCC datasets identified a signature anti-correlated to TMPRSS2. […] As proof-of-principle we also validated the anti-correlation between microRNAs and TMPRSS2 expression in a SARS-CoV-2 positive HNSCC patient tissues Finally, we did not find TMPRSS2 promoter methylation. […] Collectively, these findings suggest that tumoral tissues, herein exemplified by HNSCC and lung cancers might be more resistant to SARS-CoV-2 infection due to reduced expression of TMPRSS2.
32969768 These cells, C2BBe1 intestinal cells with a brush border having high levels of transmembrane serine protease 2 (TMPRSS2), showed robust viral propagation, and could be persistently infected with SARS-CoV-2, supporting the clinical observations of persistent GI infection in COVID-19 patients. […] Ectopic expression of viral receptors revealed that the levels of angiotensin-converting enzyme 2 (ACE2) expression confer permissiveness to SARS-CoV-2 infection, and TMPRSS2 greatly facilitates ACE2-mediated SARS-CoV-2 dissemination. […] Interestingly, ACE2 but not TMPRSS2 expression was significantly promoted by enterocytic differentiation, suggesting that the state of enterocytic differentiation may serve as a determining factor for viral propagation.
32970391 Here, the expression of five genes, known to encode coronavirus receptors/interactors (ACE2, TMPRSS2, CLEC4M, DPP4 and TMPRSS11D), was investigated in normal and cancer tissues, and their molecular relationships with clinical comorbidities were investigated. […] Their expression levels were found to be significantly altered in cancer types, including colon, kidney, liver, testis, thyroid and skin cancers (P < 0.0001); AUC > 0.80 suggests that TMPRSS2, CLEC4M and DPP4 are relevant markers of kidney, liver, and thyroid cancer, respectively.
32971472 In the lung parenchyma, ACE2 protein was found on the apical surface of a small subset of alveolar type II cells and colocalized with TMPRSS2, a cofactor for SARS-CoV2 entry.
32972339 The priming of the spike (S) protein of the virus by proteolytic cleavage by the trans-membrane serine protease-2 (TMPRSS2) is necessary for fusion of the virus to the host cell after it binds to its receptor angiotensin converting enzyme-2 (ACE2). […] In this report, we discuss the tentative therapeutic role of inhibitors of TMPRSS2, cathepsin, trypsin, furin, plasmin, factor X and elastase in infection caused by SARS-CoV-2.
32973879 We explored and collected five published and one unpublished single-cell respiratory system tissue transcriptome datasets, including idiopathic pulmonary fibrosis (IPF), aging lungs (mouse origin data), lung cancers, and smoked branchial epithelium, for specifically reanalyzing the ACE2 and TMPRSS2 expression profiles. […] Compared to normal people, we found that smoking and lung cancer increase the risk for COVID-19 infection due to a higher expression of ACE2 and TMPRSS2 in lung cells. […] IPF patients may have a lower risk for original COVID-19 infection due to lower expression in AT2 cells but may have a higher risk for severity due to a broader expression spectrum of TMPRSS2.
32974340 SARS-CoV-2 binding receptor ACE2 and the S protein priming protease TMPRSS2 are co-expressed by a subset of syncytiotrophoblasts (STB) in the first trimester and extravillous trophoblasts (EVT) in the second trimester human placenta. […] The ACE2- and TMPRSS2-positive (ACE2 + TMPRSS2 +) placental subsets expressed mRNA for proteins involved in viral budding and replication. […] Further, we discovered unique signatures of genes in ACE2 + TMPRSS2 + STBs and EVTs. […] The ACE2 + TMPRSS2 + STBs are highly differentiated cells and express genes involving mitochondrial metabolism and glucose transport. […] The second trimester ACE2 + TMPRSS2 + EVTs are enriched for markers of endovascular trophoblasts.
32979316 Drug testing confirms the efficacy of remdesivir as well as TMPRSS2 protease inhibition, validating a putative mechanism used for viral entry in alveolar cells.
32980345 Commonly used IBD medications, both biologic and non-biologic, do not significantly impact ACE2 and TMPRSS2 receptor expression in the uninflamed intestines.
32985199 SARS-CoV-2 has been shown to use the SARS-CoV receptor ACE2 for entry and serine protease TMPRSS2 for S protein.
32985513 To facilitate the development of medical approaches and novel treatments, we compared the ACE2 receptor, and TMPRSS2 and Furin proteases usage of the SARS-CoV-2 Spike glycoprotein in human and in a panel of animal models, i.e. guinea pig, dog, cat, rat, rabbit, ferret, mouse, hamster and macaque. […] Here we showed that ACE2, but not TMPRSS2 or Furin, has a higher level of sequence variability in the Spike protein interaction surface, which greatly influences Spike protein binding mode. […] In contrast, TMPRSS2 and Furin are sufficiently similar in the considered hosts not to drive susceptibility differences. […] Since TMPRSS2 and Furin are similar across species, our data also suggest that transgenic animal models expressing human ACE2, such as the hACE2 transgenic mouse, are also likely to be useful models for studies investigating viral entry.
32989429 SARS-CoV-2 cases had higher ACE2, but lower TMPRSS2, BSG/CD147, and CTSB expression compared with negative cases.
32992681 The present study aims to investigate the microRNAs that regulate the expression of hypothalamic angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), essential elements for SARS-CoV-2 cell entry. […] To determine potential hypothalamic miRNAs that can directly bind to ACE2 and TMPRSS2, multiple target bioinformatics prediction algorithms were used, including miRBase, Target scan, and miRWalk2.029. […] Our in silico analysis has revealed that, although there are over 5000 hypothalamic miRNAs, around 31 miRNAs and 29 miRNAs have shown binding sites and strong binding capacity against ACE2 and TMPRSS2, respectively. […] These novel potential hypothalamic miRNAs can be used to identify new therapeutic targets to treat neurological symptoms in COVID-19 patients via regulation of ACE2 and TMPRSS2 expression.
32992731 Proposed mechanisms involve host cell membrane-bound angiotensin-converting enzyme 2 (ACE2), type II transmembrane serine proteases (TTSPs), such as transmembrane serine protease isoform 2 (TMPRSS2), lysosomal endopeptidase Cathepsin L (CTSL), subtilisin-like proprotein peptidase furin (FURIN), and even potentially membrane bound heparan sulfate proteoglycans. […] Here, we show that the expression levels of ACE2, TMPRSS2 and other viral entry-related genes, as well as potential downstream effector genes such as bradykinin receptors, are modulated in the target organs of select disease states. […] In tissues, such as the heart, which normally express ACE2 but minimal TMPRSS2, we found that TMPRSS2 as well as other TTSPs are elevated in individuals with comorbidities compared to healthy individuals.
32993622 Abnormalities in the renin-angiotensin-aldosterone system (RAAS), angiotensin-converting enzyme-2 (ACE2) and the androgen-driven transmembrane serine protease 2 (TMPRSS2) have been elicited as key modulators of SARS-CoV-2.
32993656 We analyzed publicly available RNA microarray datasets for SARS-CoV-2 entry receptors and cofactors ACE2, TMPRSS2, BSG (CD147) and FURIN. […] We found that ACE2 and TMPRSS2 are upregulated in the airways of smokers. […] In asthmatics, ACE2 tended to be downregulated in nasal epithelium, and TMPRSS2 was upregulated in the bronchi. […] 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.
32994064 Artificial intelligence can have an important role in analysing such data to identify populations at higher risk of COVID-19-related urological pathologies and to suggest treatments that block viral entry into cells by interrupting the angiotensin-converting enzyme 2-transmembrane serine protease 2 (ACE2-TMPRSS2) pathway.
32994673 S consists of two subunits, S1 and S2, which are cleaved by the widely expressed transmembrane protease serine 2 (TMPRSS2) before the virus fuses to the plasma membrane and infects the cell. […] Current trends show that variant alleles resulting from single nucleotide polymorphisms (SNPs) of ACE2, and genetic variants of TMPRSS2, with putative distinct affinities for S clip, may determine a complex multi-factorial spectrum of SARS-CoV2 virulence across patients, and predict CoViD-19 susceptibility.
33007239 Cleavage and the syncytium are abolished by treatment with the furin inhibitors decanoyl-RVKR-chloromethylketone (CMK) and naphthofluorescein, but not by the transmembrane protease serine 2 (TMPRSS2) inhibitor camostat.
33008593 We determined the expression levels of receptor ACE2 and CD147, and serine protease TMPRSS2 in human and mouse brain cell lines and mouse different region of brain tissues with qRT-PCR and Western blot. […] ACE2 is lower but CD147 is higher expressed in mostly brain cell lines and mouse brain tissues comparing with lung cell line and tissue, and TMPRSS2 has consistent expression in brain cell lines and mouse lung tissues.
33013423 Lung immunoblot analysis of smokers, COPD and IPF subjects revealed increased abundance of proteases and receptor/spike protein like TMPRSS2, furin, and DPP4 in association with a slight increase in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor ACE2 levels. […] Overall, these findings suggest that altered transcription of target genes that regulate mitochondrial function, cellular senescence, and telomere attrition in the pathobiology of lung aging in COPD and IPF is associated with alterations in SARS-CoV-2 ACE2-TMPRSS2-Furin-DPP4 axis as pharmacological targets for COVID-19.
33015550 Additionally, transmembrane serine protease 2 (TMPRSS2) and furin facilitate virus entry into the host.
33020502 To enter host cells, the viral spike protein (S-protein) binds to its receptor, ACE2, and is then processed by TMPRSS2. […] We predict that mutations are more detrimental in ACE2 than TMPRSS2.
33024851 We collect the nasopharyngeal and oropharyngeal swabs of 63 subjects with severe symptoms or contacts with COVID-19 confirmed cases to perform a pilot-study aimed to verify the “in situ” expression of SARS-CoV-2 host invasion genes (ACE2, TMPRSS2, PCSK3, EMILIN1, EMILIN2, MMRN1, MMRN2, DPP4).
33029419 ACE2: Angiotensin-converting enzyme 2; COVID-19: coronavirus disease 2019; CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; HIV: human immunodeficiency virus; IRB, Institutional Review Board; ISH, in situ hybridisation; RT-PCR: reverse transcriptase-PCR; SARS-CoV-2, severe acute respiratory syndrome coronavirus-2; TMPRSS2: transmembrane protease, serine 2; WBC: white blood cell.
33029570 Entry of SARS-CoV-2, etiological agent of COVID-19, in the host cell is driven by the interaction of its spike protein with human ACE2 receptor and a serine protease, TMPRSS2. […] Although complex between SARS-CoV-2 spike protein and ACE2 has been structurally resolved, the molecular details of the SARS-CoV-2 and TMPRSS2 complex are still elusive. […] TMPRSS2 is responsible for priming of the viral spike protein that entails cleavage of the spike protein at two potential sites, Arg685/Ser686 and Arg815/Ser816. […] The present study aims to investigate the conformational attributes of the molecular complex between TMPRSS2 and SARS-CoV-2 spike protein, in order to discern the finer details of the priming of viral spike protein. […] Briefly, full length structural model of TMPRSS2 was developed and docked against the resolved structure of SARS-CoV-2 spike protein with directional restraints of both cleavage sites. […] The docking simulations showed that TMPRSS2 interacts with the two different loops of SARS-CoV-2 spike protein, each containing different cleavage sites. […] Key functional residues of TMPRSS2 (His296, Ser441 and Ser460) were found to interact with immediate flanking residues of cleavage sites of SARS-CoV-2 spike protein. […] Compared to the N-terminal cleavage site (Arg685/Ser686), TMPRSS2 region that interact with C-terminal cleavage site (Arg815/Ser816) of the SARS-CoV-2 spike protein was predicted as relatively more druggable. […] In summary, the present study provides structural characteristics of molecular complex between human TMPRSS2 and SARS-CoV-2 spike protein and points to the candidate drug targets that could further be exploited to direct structure base drug designing.
33031797 According to bulk RNA and single cell RNA sequencing analysis, we found that high expression of both angiotensin converting enzyme 2 (ACE2) and transmembrane Serine Protease 2 (TMPRSS2) makes the lung and intestine vulnerable to SARS-CoV-2.
33032170 For ACE2 mediated cell entry of the SARS-CoV-2, co-expression of one more protein-Transmembrane protease serine 2 (TMPRSS2) is essential. […] Existing studies suggested significant expression of ACE2 and TMPRSS2 in human vascular endothelium.
33035337 SARS-CoV-2 uses human angiotensin-converting enzyme 2 (ACE2) for viral entry and transmembrane serine protease family member II (TMPRSS2) for spike protein priming.
33042335 One of the known regulators of endocytosis is the serine protease (TMPRSS2) and AP2-associated protein kinase 1 (AAK1), which also facilitates the passage of viruses into cells. […] Furthermore, the Database of Gene expression profiling interactive analysis suggests that expression levels for ACE2, TMPRSS2, and AAK1 are positively correlated in colon cells.
33042994 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.
33043253 This work makes an assessment of wildlife susceptibility to SARS-CoV-2 by analyzing the similarities of Angiotensin Converting Enzyme 2 (ACE2) and Transmembrane Protease, Serine 2 (TMPRSS2) -both recognized as receptors and protease for coronavirus spike protein- and the genetic variation of the viral protein spike in the recognition sites. […] Comparisons of aligned sequences were made by selecting amino acids residues of ACE2, TMPRSS2 and S protein; phylogenetic trees were reconstructed using the same sequences.
33046696 Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2, an emerging virus that utilizes host proteins ACE2 and TMPRSS2 as entry factors. […] We identify expression quantitative trait loci for both ACE2 and TMPRSS2, that vary in frequency across world populations. […] We find TMPRSS2 is part of a mucus secretory network, highly upregulated by type 2 (T2) inflammation through the action of interleukin-13, and that the interferon response to respiratory viruses highly upregulates ACE2 expression.
33049061 The co-expression network was constructed by mapping the well-known angiotensin converting enzyme (ACE2), TMPRSS2, and host susceptibility genes implicated in COVID-19 genomewide association study (GWAS) onto a cornea, retinal pigment epithelium, and lung.
33049583 Then, the spike protein of SARS-CoV-2 can be cleaved and activated by transmembrane protease, serine 2 (TMPRSS2) of the host cells for SARS-CoV-2 infection. […] Therefore, ACE2 and TMPRSS2 are potential antiviral targets for treatment of prevention of SARS-CoV-2 infection. […] In this study, we discovered that 10-250 μg/mL of GB-2, from Tian Shang Sheng Mu of Chiayi Puzi Peitian Temple, can inhibit ACE2 mRNA expression and ACE2 and TMPRSS2 protein expression in HepG2 and 293 T cells without cytotoxicity. […] GB-2 treatment could decrease ACE2 and TMPRSS2 expression level of lung tissue and kidney tissue without adverse effects, including nephrotoxicity and hepatotoxicity, in animal model. […] In the compositions of GB-2, we discovered that 50 μg/mL of theaflavin could inhibit protein expression of ACE2 and TMPRSS2. […] In conclusion, our results suggest that GB-2 and theaflavin could act as potential compounds for ACE2 and TMPRSS2 inhibitors in the further clinical study.
33050360 The objective of this study is to analyze and predict the anti-protease activity of these compounds on SARS-CoV-2main protease (Mpro) and TMPRSS2 protein. […] This study has been performed by molecular docking of the compounds using PyRx with AutoDock Vina on the two aforementioned targets chosen for this study, i.e., SARS-CoV-2 Mpro and TMPRSS2.
33051876 On the contrary, the TMPRSS2 serine protease, which is known to enhance infectivity of cell-free virions, processes both S and ACE2 and increases syncytia formation by accelerating the fusion process. […] TMPRSS2 thwarts the antiviral effect of IFITMs.
33061814 Here we profiled two SARS-CoV-2 infection related genes, the transmembrane serine protease 2 (TMPRSS2) and the interferon-inducible transmembrane protein 3 (IFITM3), in human tissues and organs. […] Consistent with the expression and distribution of ACE2, TMPRSS2 was also highly expressed in digestive, urinary and reproductive systems, but low expressed in lung. […] Our data supposed that fourteen types of tumors might have different susceptibility to the virus according to ACE2, TMPRSS2 and IFITM3 expression patterns.
33062950 Highlighted are several sets of small molecules and biologics that act on specific targets, including 3CLpro, PLpro, RdRp, S-protein-ACE2 interaction, helicase/NTPase, TMPRSS2, and furin, which are involved in the viral life cycle or in other aspects of the disease pathophysiology.
33062952 Bromhexine hydrochloride showed no inhibition of TMPRSS2.
33064816 At day 111, specimens from a nasopharyngeal swab and sputum were inoculated into VeroE6/TMPRSS2 cells.( […] The culture supernatant of the VeroE6/TMPRSS2 cells cocultured with the nasopharyngeal swab was passaged to the fresh VeroE6/TMPRSS2 cells, and after 3 days of the passage, cytopathic effect was observed again.
33065278 Indeed, androgens may drive clinical results in COVID-19, through the expression of TMPRSS2, a cellular co-receptor necessary for SARS-CoV-2 infection and through androgen-mediated immune modulation.
33065601 Data from several preclinical and clinical reports suggest a lower susceptibility for COVID-19 in patients with underlying type 2 airway inflammation including asthma that may be related to a reduced expression of ACE2 and TMPRSS2 receptors for SARS-CoV-2. […] Corticosteroids further decrease expression of the ACE2 and TMPRSS2 receptors, hence may also have a protective effect against infection with SARS-CoV-2. […] Underrepresentation of SARS-CoV-2-infected patients with asthma and related allergic diseases may be based on potentially protective underlying mechanisms, such as type 2 airway inflammation, downregulation of ACE2/TMPRSS2 receptors, reduced exposures to triggers and improved adherence to controller medications.
33066495 As such, this paper focuses on the potential role of BPA in promoting comorbidities associated with severe COVID-19, as well as on potential BPA-induced effects on key SARS-CoV-2 infection mediators, such as angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). […] Interestingly, GPR30 appears to exhibit greater co-localisation with TMPRSS2 in key tissues like lung and prostate, suggesting that BPA exposure may impact on the local expression of these SARS-CoV-2 infection mediators.
33069705 In here, exploiting a large panel of publicly available genome-wide data, we investigated whether the human receptor ACE2 and human proteases TMPRSS2, FURIN and CATHEPSINs (B, L and V), which are involved in SARS-CoV-2 cell entry, are transcriptionally regulated by environmental cues. […] We further demonstrate that transcription factor AhR, which is commonly activated by pollutants, binds to the promoter of TMPRSS2 and enhancers and/or promoters of Cathepsin B, L and V encoding genes.
33072093 Therefore, the development of novel inhibitors of ACE2/TMPRSS2 is likely to be beneficial in combating SARS-CoV-2 infections.
33072849 Genetic variants of proteases associated with SARS-CoV-2 entry (TMPRSS2, CTSB, and CTSL) are strongly associated with their expression variation, suggesting a genetic contribution to phenotypic variations in multiple organs upon virus attack.
33081421 To address the expression pattern of the SARS-CoV-2 receptor ACE2 and the viral priming protease TMPRSS2 in the respiratory tract, this study investigated RNA sequencing transcriptome profiling of samples of airway and oral mucosa. […] TMPRSS2 is highly expressed in small airway epithelium and nasal epithelium and has lower expression in masticatory mucosa.
33091758 The evidence of transmembrane protease, serine 2 (TMPRSS2) expression in lung tissue, which is an androgen-regulated gene and expressed mainly in the adult prostate may interpret the increased susceptibility of the male gender to severe COVID-19 complications.
33098835 Bioactive peptides with unique amino acid sequences can mitigate such targets including, type II transmembrane serine proteases (TMPRSS2) inhibition, furin cleavage, and renin-angiotensin-aldosterone system (RAAS) members.
33108902 Considering the limited data on cancer patients, we analyzed public data repositories limited to investigate angiotensin-converting enzyme 2 (ACE2) and the transmembrane serine protease 2 (TMPRSS2) expressions and genetic variants to identify the basis of individual susceptibility to SARS-CoV-2. […] Allele frequencies of germline variants were explored in different ethnicities, with a special focus on ACE2 variants located in the binding site to SARS-CoV-2 spike protein.The analysis of ACE2 and TMPRSS2 expressions in healthy tissues showed a higher expression in the age class 20 to 59 years (false discovery rate [FDR] < 0.0001) regardless of gender. […] ACE2 and TMPRSS2 were more expressed in tumors from males than females (both FDR < 0.0001) and, opposite to the regulation in tissues from healthy individuals, more expressed in elderly patients (FDR = 0.005; FDR < 0.0001, respectively). […] ACE2 and TMPRSS2 expressions were higher in cancers of elderly patients compared with healthy individuals (FDR < 0.0001). […] The mechanisms of ACE2 and TMPRSS2 regulation could be targeted for preventive and therapeutic purposes in the whole population and especially in cancer patients.Further studies are needed to show a direct correlation of ACE2 and TMPRSS2 expressions in cancer patients and the incidence of COVID-19.
33110240 We discussed a possible link between the activation of hypoxia inducible factor 1α (HIF-1α) and cell entry of SARS-CoV-2, since HIF-1α is shown to suppress the angiotensin-converting enzyme 2 (ACE2) receptor and transmembrane protease serine 2 (TMPRSS2) and upregulate disintegrin and metalloproteinase domain-containing protein 17 (ADAM17).
33117379 Therefore, the occurrence of specific comorbidities associated with renin-angiotensin system (RAS) imbalance mediated by the interaction between angiotensin-converting enzyme 2 (ACE2) and desintegrin and metalloproteinase domain 17 (ADAM17), along with specific genetic factors mainly associated with type II transmembrane serine protease (TMPRSS2) expression, could be decisive for the clinical outcome of COVID-19. […] Therefore, in this review, we focus on the main pathophysiological aspects of ACE2, ADAM17, and TMPRSS2 host proteins in COVID-19. […] Additionally, we discuss a possible mechanism to explain the deleterious effect of ADAM17 and TMPRSS2 over-activation in the COVID-19 outcome.
33119197 Most, but not all, transcriptomic and proteomic analyses fail to observe the putative SARS-CoV-2 receptor, angiotensin converting enzyme-2, or the cellular serine protease necessary for viral entry, TMPRSS2, on platelets and megakaryocytes.
33122999 Therefore, we carried out immunostainings for ACE2 and TMPRSS2, two proteinases crucial for the entry of SARS-CoV2 into host cells, in the human enteric nervous system (ENS), as well as in the choroid plexus of the lateral ventricles. […] We found that ACE2 and TMPRSS2 are expressed by enteric neurons and glial cells of the small and large intestine, as well as choroid plexus epithelial cells, indicating that these cells meet the molecular requirements for viral entry.
33125431 Angiotensin-converting enzyme 2 (ACE2) has been implicated in the pathogenesis of chronic kidney disease (CKD) and is a membrane receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease (COVID-19), whereas transmembrane protease, serine 2 (TMPRSS2) is involved in viral attachment. […] Together, tissue expression of ACE2 and TMPRSS2 may determine infection. […] Sex, age, body mass index (BMI), and CKD are clinical risk factors for COVID-19 severity, but the relationships between kidney ACE2 and TMPRSS2 expression and these clinical variables are unknown. […] TMPRSS2 expression was similar in the tubulointerstitium but lower in glomeruli of CKD patients compared to HLD (P < 0.0001). […] There was a strong relationship between ACE2 and TMPRSS2 expression in the glomerulus (r = 0.51, P < 0.0001). […] There were no relationships between TMPRSS2 expression and clinical variables. […] In summary, kidney expression of ACE2 and TMPRSS2 differs in HLD and CKD.
33126048 The entry receptors for SARS-CoV-2 - ACE2 and TMPRSS2 are expressed in placenta.
33130280 Herein, we selected transmembrane protease serine 2 (TMPRSS2) enzyme, a potential pharmacological target against SARS-CoV-2, involved in the spread and pathogenesis of the virus. […] Since 3D structure is not available for this protein, the present study aims at homology modelling and validation of TMPRSS2 using Swiss-model server. […] Validation of the modelled TMPRSS2 using various online tools confirmed model accuracy, topology and stereochemical plausibility. […] The catalytic triad consisting of Serine-441, Histidine-296 and Aspartic acid-345 was identified as active binding site of TMPRSS2 using existing ligands. […] Molecular docking studies of various drugs and phytochemicals against the modelled TMPRSS2 were performed using camostat as a standard drug. […] In conclusion, the study unravelled eight high affinity binding compounds, which may serve as potent antagonists against TMPRSS2 to impact COVID-19 drug therapy.
33137894 SARS-CoV2 infection depends on the host cell Angiotensin-Converting Enzyme-2 (ACE2) and Transmembrane Serine Protease-2 (TMPRSS2), where the virus uses ACE2 for entry and TMPRSS2 for S protein priming. […] The TMPRSS2 gene encodes a Transmembrane Protease Serine-2 protein (TMPS2) that belongs to the serine protease family.
33141332 The current body of evidence indicates that SARS-CoV‑2 requires the membrane-bound angiotensin-converting enzyme 2 (ACE2) and the membrane-bound serine protease TMPRSS2 to enter cells. […] Recent studies suggest that COVID-19 patients rarely exhibit viral RNA in tear film and conjunctival smears and that, ACE2 and TMPRSS2 are only expressed in small amounts in the conjunctiva, making conjunctival infection with SARS-CoV‑2 via these mediators unlikely.
33143053 The two main co-factors needed by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to enter human cells are angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). […] Here, we focused on the study of microRNAs that specifically target TMPRSS2. […] Since we and others have shown that endothelial cells play a pivotal role in the pathogenesis of the coronavirus disease 2019 (COVID-19), we mechanistically validated miR-98-5p as a regulator of TMPRSS2 transcription in two different human endothelial cell types, derived from the lung and from the umbilical vein. […] Taken together, our findings indicate that TMPRSS2 represents a valid target in COVID-19 treatment, which may be achieved by specific non-coding-RNA approaches.
33148439 Additionally, we tested the association of genetic variants in two key genes related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2), with COVID-19 or any other phenotypes. ), was obtained.
33150674 For a virus to be pathogenic, in addition to its affinity (tropism) for specific tissue(s), host cells must allow viral entry, and discuss the important role played by transmembrane protease, serine 2 (TMPRSS2) and coexpression of both ACE2 and TMPRSS2 in the same cells is important to cause damage. […] Lack of coexpression of ACE2 and TMPRSS2 in the same cells of the kidneys is the limiting factor of SARS-CoV-2 direct effects in the kidney.
33153216 The expression of apparatus mediating SARS-CoV-2 entry, including angiotensin-converting enzyme 2, transmembrane protease serine 2 (TMPRSS2) and a disintegrin and metalloprotease 17 (ADAM17), within the renal tubular cells is highly associated with acute kidney injury mediated by SARS-CoV-2.
33153403 : ACE2, angiotensin converting enzyme II; βCoV, betacoronavirus; COVID-19, Coronavirus Disease 2019; CQ, chloroquine; DMV, double-membrane vesicle; GI, gastrointestinal; HCQ, hydroxychloroquine; IL, interleukin; MAP1LC3/LC3, microtubule associated protein 1 light chain 3; MEFs, mouse embryonic fibroblasts; MERS-CoV, Middle East respiratory syndrome coronavirus; MHV, murine hepatitis virus; PE, phosphatidylethanolamine; SARS-CoV, severe acute respiratory syndrome coronavirus; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TMPRSS2, transmembrane serine protease 2; TNF, tumor necrosis factor; WHO, World Health Organization.
33156843 Analyses of single-cell RNA sequencing data show that co-expression of ACE2 and TMPRSS2 is elevated in absorptive enterocytes from the inflamed ileal tissues of Crohn disease patients compared to uninflamed tissues, revealing shared pathobiology between COVID-19 and inflammatory bowel disease.
33159236 The broad infective capacity of SARS-CoV-2 is related to the pattern of expression of the viral entry factors ACE2 and TMPRSS2 in human tissues. […] As such, the respiratory and gastrointestinal tracts are at high risk for SARS-CoV-2 infection due to their high expression of ACE2 and TMPRSS2, which explains the clinical phenotype described in the vast majority of infected patients that includes pneumonia and diarrhea. […] Although there is little evidence of the expression of ACE2 and TMPRSS2 in the normal skin, the dermatological findings observed among COVID-19 patients warrants further investigation to delineate the mechanisms of skin affection after SARS-CoV-2 infection.
33164230 There is growing evidence that androgen-enabled expression of ACE2 receptors and the serine protease TMPRSS2, two permissive elements engaging the SARS-CoV-2 spike protein for infection, may contribute to severe COVID-19 in men.
33168188 The host-cell receptor angiotensin converting enzyme 2 (ACE2) and the type II transmembrane serine protease (TMPRSS2) are important for viral cell entry. […] It is unclear whether obesity alters expression of Ace2 and Tmprss2 in the lower respiratory tract. […] Here, we show that: 1) Ace2 expression is elevated in the lung and trachea of diet-induced obese male mice and reduced in the esophagus of obese female mice relative to lean controls; 2) Tmprss2 expression is increased in the trachea of obese male mice but reduced in the lung and elevated in the trachea of obese female mice relative to lean controls; 3) in chow-fed lean mice, females have higher expression of Ace2 in the lung and esophagus as well as higher Tmprss2 expression in the lung but lower expression in the trachea compared to males; and 4) in diet-induced obese mice, males have higher expression of Ace2 in the trachea and higher expression of Tmprss2 in the lung compared to females, whereas females have higher expression of Tmprss2 in the trachea relative to males. […] Our data indicate diet- and sex-dependent modulation of Ace2 and Tmprss2 expression in the lower respiratory tract and esophagus.
33170176 In addition, we identified possible interactions among hydroxytyrosol and alpha-cyclodextrin with the protein Spike and the human proteins ACE2 and TMPRSS2.
33174447 These proteins include the viral receptor, angiotensin-converting enzyme 2 (ACE2), and the proteases, transmembrane serine protease 2 (TMPRSS2) and furin. […] During cellular differentiation, we measured the expression of ACE2, TMPRSS2, and furin over progressive ALI days by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blot, and immunofluorescence staining. […] Like ACE2, TMPRSS2 and furin proteins are localized in differentiated ciliated cells, as confirmed by immunofluorescence staining.
33176395 For the virus to engage in host membrane fusion, SARS-CoV-2 utilizes the human transmembrane surface protease, TMPRSS2, to cleave and activate the spike protein. […] Camostat mesylate, an orally available well-known serine protease inhibitor, is a potent inhibitor of TMPRSS2 and has been hypothesized as a potential antiviral drug against COVID-19. […] In mice, camostat mesylate treatment during acute infection with influenza, also dependent on TMPRSS2, leads to a reduced viral load.
33177848 Based on previously published evidence, ACE2 and TMPRSS2 are both pivotal entry molecules that enable cellular infection by SARS-CoV-2. […] We investigated the expression pattern of ACE2 and TMPRSS2 in major organs in the human body, especially in specific disease conditions. […] Our results revealed that ACE2 and TMPRSS2 were highly expressed in genitourinary organs.
33179220 SARS-COV2 virus spike proteins utilize Transmembrane protease serine 2 (TMPRSS2) for host entry. […] Androgen receptors are transcription promoters for TMPRSS2 and can, therefore, facilitate SARS-COV2 entry. […] Androgen’s TMPRSS2-mediated actions might explain both the low fatalities observed in prepubertal children and the differences between sexes regarding SARS-COV2 infection.
33180746 Integrating single-cell RNA sequencing (scRNA-seq) of developing mouse lung with temporally resolved immunofluorescence in mouse and human lung tissue, we found that expression of SARS-CoV-2 Spike protein primer TMPRSS2 was highest in ciliated cells and type I alveolar epithelial cells (AT1), and TMPRSS2 expression increased with aging in mice and humans. […] SARS-CoV-2 RNA was highly colocalized in cells expressing TMPRSS2. […] Together, these data demonstrate the cellular spectrum infected by SARS-CoV-2 in lung epithelium and suggest that developmental regulation of TMPRSS2 may underlie the relative protection of infants and children from severe respiratory illness.
33182653 SARS-CoV-2 interacts with angiotensin-converting enzyme 2 and TMPRSS2, which is a serine protease both expressed in lungs, the gastro-intestinal tract, and cardiac myocytes.
33183102 enzymes, and RdRp and TMPRSS2 genes show capability to produce effective anti-SARS-CoV-2 action.
33186749 Immunostaining for viral entry receptor ACE2 and SARS-CoV-2 spike protein priming protease TMPRSS2 showed broad expression in the gastrointestinal tract with highest levels in the intestine, the latter faithfully recapitulated by PSC-HIOs.
33188579 Angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2) are the main host cell factors for the Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) entry but so far it is unclear if human MSCs express or do not these two proteins. […] To elucidate these important aspects, we evaluated if human MSCs from both fetal and adult tissues constitutively express ACE2 and TMPRSS2 and, most importantly, if they can be infected by SARS-CoV-2. […] ACE2 and TMPRSS2 were expressed by the SARS-CoV-2-permissive human pulmonary Calu-3 cell line but not by all the MSCs tested.
33189768 Here, we summarize the current status of peptides inhibiting SARS-CoV-2 entry and outline the strategies used to design peptides targeting the ACE2 receptor or the viral spike protein and its activating proteases furin, transmembrane serine protease 2 (TMPRSS2), or cathepsin L.
33193689 The function of TMPRSS2 in the dataset was further verified by gene set enrichment analysis (GSEA). […] In conclusion, the expression of TMPRSS2 is significantly increased in PRAD, elevated TMPRSS2 is associated with immune infiltration, and prognosis is positively correlated.
33195212 To explore the susceptibility factors of cancer patients, we assessed the expression of ACE2, TMPRSS2, and the endocytic regulator AAK1 in lung adenocarcinoma (LUAD) patients and explored their effects on immune infiltration. […] We found that the expression of ACE2 and TMPRSS2 in LUAD patients was significantly increased, which may explain why LUAD patients are susceptible to SARS-CoV-2, and the patients with high-expression genes presented increased infiltration of immune cells such as B cells and CD4 T cells.
33195400 Further studies revealed the integral role of proteases (TMPRSS2, cathepsins, plasmin, etc.) in viral entry and the immune system.
33195487 Here the virus can directly infect vascular tissues, via TMPRSS2 spike glycoprotein priming, thereby facilitating ACE-2-mediated viral entry.
33196058 SARS-CoV-2 appears to infect cells by first binding and priming its viral-spike proteins with membrane-associated angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). […] Through the coordinated actions of ACE2 and TMPRSS2, SARS-CoV-2 spike proteins fuse with plasma membranes and ultimately the virus enters cells.
33199671 We also identified miRNAs that bind to receptor proteins, such as ACE2, ADAM17, and TMPRSS2, which are important for understanding the infection mechanism of SARS-CoV-2.
33200417 The renin-angiotensin system (RAS), also ACE 2 and TMPRSS2 play an important role in the cellular entry for SARS-CoV-2.
33205496 This literature review provides an overview of recent studies of genetic polymorphisms in genes that mediate the SARS-CoV-2 infection mechanism (ACE1, ACE2, TMPRSS2 and CD26).
33207245 This would require binding and entry of SARS-CoV-2 into β cells via co-expression of its canonical cell entry factors, angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2); however, their expression in human pancreas has not been clearly defined. […] We analyzed six transcriptional datasets of primary human islet cells and found that ACE2 and TMPRSS2 were not co-expressed in single β cells. […] In pancreatic sections, ACE2 and TMPRSS2 protein was not detected in β cells from donors with and without diabetes. […] Instead, ACE2 protein was expressed in islet and exocrine tissue microvasculature and in a subset of pancreatic ducts, whereas TMPRSS2 protein was restricted to ductal cells. […] These findings reduce the likelihood that SARS-CoV-2 directly infects β cells in vivo through ACE2 and TMPRSS2.
33207533 We provide a collection of high-probability miRNA binding sites within the SARS-CoV-2 genome as well as within mRNA transcripts of critical viral entry proteins ACE2 and TMPRSS2 and their upstream modulators, the interferons (IFN). […] In particular, we identify predicted miRNA binders to SARS-CoV-2 ORFs (miR-23a (1ab), miR-29a, -29c (1ab, N), miR-151a, -151b (S), miR-4707-3p (S), miR-298 (5’-UTR), miR-7851-3p (5’-UTR), miR-8075 (5’-UTR)), ACE2 3’-UTR (miR-9-5p, miR-218-5p), TMPRSS2 3’-UTR (let-7d-5p, -7e-5p, miR-494-3p, miR-382-3p, miR-181c-5p), and IFN-α 3’-UTR (miR-361-5p, miR-410-3p).
33210729 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry factors, ACE2 and TMPRSS2, are highly expressed in nasal epithelial cells. […] The expression of ACE2 and TMPRSS2 was assessed in nasal tissues of control subjects and eosinophilic CRSwNP (ECRSwNP) and nonECRSwNP patients. […] The correlations between ACE2/TMPRSS2 expression and inflammatory indices of CRSwNP endotypes were evaluated. […] Regulation of ACE2/TMPRSS2 expression by inflammatory cytokines and glucocorticoids was investigated. […] TMPRSS2 expression was decreased in nasal tissues of CRSwNP patients compared to control subjects and not correlated with the inflammatory endotypes of CRSwNP. […] Glucocorticoid treatment decreased ACE2 expression in nasal tissues of nonECRSwNP patients, but not in ECRSwNP patients, whereas TMPRSS2 expression was not affected.
33210953 (papain-like protease), RdRp (RNA-dependent RNA polymerase), S protein (viral spike glycoprotein), TMPRSS2 (transmembrane protease serine 2), ACE2 (angiotensin-converting enzyme 2), and AT2 (angiotensin AT2 receptor) are important targets.
33216184 COVID-19 is a respiratory infectious disease and SARS-CoV-2 replication and shedding occurs in nasal and bronchial epithelial respiratory cells through the interaction with ACE2 and TMPRSS2 receptors, both overexpressed in smokers and former smokers.
33218024 Furthermore, three of the top 30 drugs with strong affinity prediction for the TMPRSS2 are anti-hepatitis C virus (HCV) drugs, including ombitasvir, daclatasvir, and paritaprevir. […] Notably, of the top 30 drugs, AT1R blocker eprosartan and neuropsychiatric drug lisuride showed similar gene expression profiles to potential TMPRSS2 inhibitors. […] Collectively, we suggest that drugs predicted to have strong inhibitory potencies to ACE2 and TMPRSS2 through the DTI model should be considered as potential drug repurposing candidates for COVID-19.
33236375 Multi-organ injuries have been reported by describing potential SARS-CoV-2 entrance routes: ACE2 and TMPRSS2. […] Expression of ACE2 and TMPRSS2 at RNA or protein level has been reported across various investigations indicates that the male genitalia potentially is vulnerable to SARS-CoV-2 infection.
33241508 SARS-CoV-2 uses ACE2 combined with the transmembrane protease serine 2 (TMPRSS2) as the key molecular complex to infect the host cells. […] Interestingly, ACE2 and TMPRSS2 expression levels are high in the thyroid gland and more than in the lungs.
33242791 Here, we report that human MSCs barely express ACE2 and TMPRSS2, two receptors required for the virus endocytosis, indicating that MSCs are free from SARS-CoV-2 infection. […] Furthermore, we observed that MSCs were unable to induce the expression of ACE2 and TMPRSS2 in epithelial cells and macrophages. […] Importantly, under different inflammatory challenge conditions, implanted human MSCs failed to up-regulate the expression of ACE2 and TMPRSS2 in the lung tissues of mice.
33243116 In this report, we focus on the role of host cell proteases (ACE2, ADAM17, TMPRSS2) and androgen receptor (AR) in SARS-CoV-2 infection. […] The hypotheses put forth by us are based on the role played by the proteases ACE2, ADAM17, TMPRSS2 and AR in SARS-CoV-2 infection which were deduced based on various studies.
33244161 The novel coronavirus SARS-CoV-2 enters into the human body mainly through the ACE2 + TMPRSS2+ nasal epithelial cells.
33245471 The ACE2 receptor is, so far, the best-known host factor for SARS-CoV-2 entry, but another essential element, the TMPRSS2 protease, has recently been identified. […] Here, we have analysed TMPRSS2 expression data in the lung correlating them with age, sex, diabetes, smoking habits, exposure to pollutant and other stimuli, in order to highlight which factors might alter TMPRSS2 expression, and thus impact the susceptibility to infection and COVID-19 prognosis. […] Moreover, we reported TMPRSS2 polymorphisms affecting its expression and suggested the ethnic groups more prone to COVID-19. […] Finally, we also highlighted a gender-specific co-expression between TMPRSS2 and other genes related to SARS-CoV-2 entry, maybe explaining the higher observed susceptibility of infection in men.
33245731 TMPRSS2, inflammatory cytokines G-CSF, M-CSF, IL-1α, IL-6 and MCP-1 are suppressed by MEKi alone or with remdesivir.
33254487 In particular, we refer to the TMPRSS2 expression profile, balance of androgen and estrogen, blood group-A and/or B, nonsynonymous mutations in ORF3, and proteins NS7b and NS8 in SARS-CoV-2.
33254575 Further, cleavage of the viral spike protein (S) by the proteases like transmembrane serine protease 2 (TMPRSS2) or Cathepsin L (CTSL) is essential to effectuate host cell membrane fusion and virus infectivity. […] Based on the human tissue specific distribution of SARS-CoV-2 cell entry factors ACE2 and TMPRSS2 and other supportive evidence from the literature, we hypothesize that SARS-CoV-2 host cell entry receptor-ACE2 based mechanism in GI tissue may be involved in COVID-19 (i) in the pathogenesis of digestive symptoms, (ii) in increased diabetic complications, (iii) in disease recurrence.
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.
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.
33268377 I hypothesize that several membrane-associated serine proteinases (MASPs), in synergy with or in place of TMPRSS2, contribute to activate the SARS-CoV-2 spike protein.
33270927 Overexpression of TMPRSS2, which increases plasma membrane fusion versus endosome fusion of SARS-CoV-2, attenuated IFITM3 restriction and converted amphipathic helix mutants into infection enhancers.
33278189 The virus requires proteolytic processing of its spike protein by transmembrane protease receptor serine type 2 (TMPRSS2) to enable binding to cellular ACE2. […] Since TMPRSS2 contains an androgen promoter, it may be downregulated by the antiandrogenic actions of spironolactone. […] We review the evidence that spironolactone may be the preferred RASSi to increase PN1 and decrease TMPRSS2, furin and plasmin activities and thereby to reduce viral cell binding, entry, infectivity and bad outcomes.
33278516 TMPRSS2 gene is expressed in many human tissues and plays a critical role in spreading the infection of the viruses including coronavirus and progression of prostate cancer, and hence could be used as a potential drug target. […] There are limited reports on occurrence of genetic polymorphism of ACE2 and TMPRSS2 in general population, expressions in pathological conditions, and its impact on COVID-19 disease. […] Hence we comprehended the occurrence of ACE2, TMPRSS2 polymorphism in general population, expression in various diseases and its impact on COVID-19 disease. […] There are diversities in distribution of ACE2 and TMPRSS2 polymorphisms among different populations. […] Analyzing the genetic variants and expression of ACE2 and TMPRSS2 genes, in a population may provide the genetic marker for susceptibility or resistance against the coronavirus infection, which might be useful for identifying the susceptible population groups for targeted interventions and for making relevant public health policy decisions.
33289233 Bioinformatic analysis indicated co-expression of binding related proteins of SARS-COV-2 (ACE2, TMPRSS2 and Furin) in small intestine.
33289868 At the time of the research, angiotensin-converting enzyme 2 (ACE2) was clearly identified as the receptor and transmembrane serine protease 2 (TMPRSS2) as the necessary protease to enable the infection of human cells with SARS-CoV‑2. […] In the eye both ACE2 and TMPRSS2 are expressed, although sometimes very weakly and with varying degrees in different tissues. […] According to current state of knowledge the eye is not considered to be a high-risk tissue due to the low ACE2 and TMPRSS2 expression.
33290397 The host serine protease TMPRSS2 and cysteine proteases Cathepsin B/L can activate S, making two independent entry pathways accessible to SARS-CoV-2.
33292131 Using different bioinformatics tools, the expression and methylation patterns of ACE2 and TMPRSS2 were analyzed in healthy and malignant tissues, focusing on lung adenocarcinoma and data were correlated to clinical parameters and smoking history. […] ACE2 and TMPRSS2 were heterogeneously expressed across 36 healthy tissues with the highest expression levels in digestive, urinary and reproductive organs, while the overall analysis of 72 paired tissues demonstrated significantly lower expression levels of ACE2 in cancer tissues when compared to normal counterparts. […] In contrast, ACE2, but not TMPRSS2, was overexpressed in LUAD, which inversely correlated to the promoter methylation. […] TMPRSS2 expression in non-neoplastic lung tissues was heterogeneous and dependent on sex and smoking history, while it was downregulated in LUAD of smokers. […] Cancer progression was associated with a decreased TMPRSS2, but unaltered ACE2. […] In contrast, ACE2 and TMPRSS2 of lung metastases derived from different cancer subtypes was higher than organ metastases of other sites. […] TMPRSS2, but not ACE2, was associated with LUAD patients’ survival. […] Comprehensive molecular analyses revealed a heterogeneous and distinct expression and/or methylation profile of ACE2 and TMPRSS2 in healthy lung vs. 
33292872 By using publicly available datasets we qualified epithelial ACE2 expression in human intestine, and assessed gene co-expression of ACE2 and SARS-CoV-2 priming Transmembrane Serine Protease 2 (TMPRSS2) with nAChRs in intestinal epithelial cells. […] We show co-expression of ACE2 and TMPRSS2 with nAChRs and α7 nAChR in particular in intestinal stem cells, goblet cells, and enterocytes. […] ACE2 and TMPRSS2 are specifically expressed in epithelial cells of human intestine, and both are co-expressed with nAChRs.
33296096 Intracellular entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) depends on the interaction between its spike protein with the cellular receptor angiotensin-converting enzyme 2 (ACE2) and depends on Furin-mediated spike protein cleavage and spike protein priming by host cell proteases, including transmembrane protease serine 2 (TMPRSS2). […] As the expression of ACE2, TMPRSS2, and Furin in the middle and inner ear remain unclear, we analyzed the expression of these proteins in mouse ear tissues. […] We performed immunohistochemical analysis to examine the distribution of ACE2, TMPRSS2, and Furin in the Eustachian tube, middle ear spaces, and cochlea of mice. […] TMPRSS2 was expressed in both the nucleus and cytoplasm in the middle spaces, with the expression being stronger in the nucleus in the mucosal epithelium of the middle ear spaces and Eustachian tube. […] TMPRSS2 was present in the cytoplasm in the organ of Corti and stria vascularis and in the nucleus and cytoplasm in the spiral ganglion. […] ACE2, TMPRSS2, and Furin are diffusely present in the Eustachian tube, middle ear spaces, and cochlea, suggesting that these tissues are susceptible to SARS-CoV-2 infection.
33297431 Sequential cleavage of viral S protein by furin and transmembrane serine protease 2 (TMPRSS2) triggers viral entry to release the viral genome into the target cell. […] Hence, TMPRSS2 and furin are possible drug targets.
33298875 The p.Val197Met missense variant that affects the stability of the TMPRSS2 protein displays a decreasing allele frequency among the severe patients compared to the mild and the general population.
33301987 Here, we used diversity analysis of the angiotensin I converting enzyme 2 (ACE2) that serves as cellular receptor for SARS-CoV-2 and transmembrane protease serine 2 (TMPRSS2), which has been proved to be utilized by SARS-CoV-2 for spike protein priming.
33301988 It is known that SARS-CoV-2 is dependent on TMPRSS2 activity for entrance and subsequent infection of the host cells and TMPRSS2 is a host cell molecule that is important for the spread of viruses such as coronaviruses. […] TMPRSS2 protein is highly expressed in prostate secretory epithelial cells, and its expression is dependent on androgen signals. […] One of the molecular signs of prostate cancer is TMPRSS2-ERG gene fusion. […] In TMPRSS2-ERG-positive prostate cancers different patterns of changed gene expression can be detected. […] The possible molecular relation between fusion positive prostate cancer patients and the increased risk of lethal respiratory viral infections especially SARS-CoV-2 can candidate TMPRSS2 as an attractive drug target. […] This review attempts to investigate the possible relation between the gene expression pattern that is produced through TMPRSS2-ERG fusion positive prostate cancer and the possible influence of these fluctuations on the pathogenesis and development of viral infections such as SARS-CoV-2.
33305659 We hypothesize that anti-SARS-CoV-2 activity depends in part on this AR downregulation through diminished TMPRSS2 expression and modulation of ACE2 activity.
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.
33312128 Several studies have been carried out to ascertain the presence of SARS-CoV-2 in the seminal fluid, with contrasting results; the expression of angiotensin-converting enzyme-2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) in the testes and in the male genital tract led to speculation about the possible presence of the virus in the seminal fluid. […] However, it was found that ACE2 and TMPRSS2, used by the virus to enter host cells, are expressed differently in certain testicle cells (stem germ cells, Leydig and Sertoli cells), yet the testicle cells in which ACE2 and TMPRSS2 molecules are simultaneously expressed are rare.
33315943 Recent data suggests a high concentration of SARS-Cov2 receptors, ACE2 or TMPRSS2, in nasal epithelium and cornea, which explains person-to-person transmission. […] We did not detect significant expression of either ACE2 or TMPRSS2 in the normal human myometrium, uterus, ovaries, fallopian tube, or breast. […] Furthermore, none of the cell types in the female reproductive organs we investigated, showed the co-expression of ACE2 with proteases, TMPRSS2, Cathepsin B (CTSB), and Cathepsin L (CTSL) known to facilitate the entry of SARS2-CoV2 into the host cell.
33318519 Cell entry of SARS-CoV-2, the novel coronavirus causing COVID-19, is facilitated by host cell angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). […] We aimed to identify and characterize genes that are co-expressed with ACE2 and TMPRSS2, and to further explore their biological functions and potential as druggable targets. […] TMPRSS2 was in a module of 1,086 co-expressed genes; 31 of these genes were enriched in the gene ontology biologic process ‘receptor-mediated endocytosis’, and 52 TMPRSS2-correlated genes had known interactions with drug compounds. […] Dozens of genes are co-expressed with ACE2 and TMPRSS2, many of which have plausible links to COVID-19 pathophysiology.
33324224 SARS-CoV-2 appears to infect cells by first binding viral spike proteins with host protein angiotensin-converting enzyme 2 (ACE2) receptors; the virus is endocytosed following priming by transmembrane protease serine 2 (TMPRSS2).
33328008 Angiotensin-converting enzyme 2 (ACE2), one of the binding sites for SARS-CoV-2 infection in humans, can bind to viral spike proteins, allowing transmembrane serine protease (TMPRSS2) to activate S-protein to trigger infection and induce the production of various inflammatory factors such as interleukin-1, interferon-l, and tumor necrosis factor. […] Compared with adults, children tend to have lower expression levels of ACE2 and TMPRSS2, which are presumed to be associated with milder symptoms and fewer cases in children.
33329480 Our molecular modeling and docking analysis identified that D614G mutation resulted in enhanced affinity of Spike S1-S2 hinge region with TMPRSS2 protease, possibly the reason for increased shedding of S1 domain in G614 as compared to D614.
33330557 In addition, Transmembrane serine protease 2 (TMPRSS2) can enhance ACE2-mediated virus entry. […] Studies have found that ACE2 and TMPRSS2 are expressed in the testis and male reproductive tract and are regulated by testosterone.
33351362 The researchers explain the effect of the therapy by the effect on the TMPRSS2 protein. […] It was found that both TMPRSS2 expression and a more severe course of coronavirus infection are observed in men with hyperandrogenism - androgenic alopecia, acne, excessive facial hair growth and increased skin oiliness.
33352869 Intracellular infiltration of the SARS-CoV2 virus particles into the epithelial cells in lungs are facilitated by the spike glycoprotein (S Protein) on the outer side of the virus envelope, a membrane protein ACE2 (angiotensin-converting enzyme 2) and two proteases (TMPRSS2 and Furin) in the host cell.
33359190 Tmprss2 is an emerging molecular target which guides cellular infections of SARS-CoV-2, has been earmarked for interventions against the viral pathologies. […] The study aims to computationally screen and identifies potential miRNAs, following in vitro experimental validation of miRNA-mediated suppression of Tmprss2 for early prevention of COVID-19. […] Pool of 163 miRNAs, scrutinized for Tmprss2 binding with three miRNA prediction algorithms, ensued 11 common miRNAs. […] Further, computational negative energies for association, corroborated miRNA-Tmprss2 interactions, whereas three miRNAs (hsa-miR-214, hsa-miR-98 and hsa-miR-32) based on probability scores ≥0.8 and accessibility to Tmprss2 target have been selected in the Sfold tool. […] Transfection of miRNA(s) in the Caco-2 cells, quantitatively estimated differential expression, confirming silencing of Tmprss2 with maximum gene suppression by hsa-miR-32 employing novel promising role in CoV-2 pathogenesis. […] The exalted binding of miRNAs to Tmprss2 and suppression of later advocates their utility as molecular tools for prevention of SARS-CoV-2 viral transmission and replication in humans.
33362565 Recently, A1AT has been found to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by inhibiting transmembrane serine protease 2 (TMPRSS2), a protease involved in the entry of SARS-CoV-2 into host cells.
33362695 We found that the mRNAs encoding the ACE2 receptor and the TMPRSS2 transmembrane serine protease, both of which are required for viral entry into host cells, are minimally expressed in the major cell types of the brain.
33364539 The review has been compiled using references from major databases such as Web of Science, PubMed, Scopus, Elsevier, Springer and Google Scholar (up to June 2020) and keywords such as ‘coronaviruses’, ‘marine organisms’, ‘biologically active substances’, ‘antiviral drugs’, ‘SARS-CoV’, ‘MERS-CoV’, ‘SARS-CoV-2’, ‘3CLpro’, ‘TMPRSS2’, ‘ACE2’.
33369281 Although pulmonary epithelial cells may rely mainly on plasma membrane serine protease TMPRSS2 for cell entry, PPIs/NHEIs might be efficacious in ACE2-expressing cells where viral endocytosis is the major or a contributing entry pathway.
33372179 Since AT2 cells express the SARS-CoV-2 receptors angiotensin converting enzyme (ACE2) and transmembrane protease/serine subfamily member 2 (TMPRSS2), their expression should decline as AT2 cells are depleted by hyperoxia. […] It also stimulated expression of TMPRSS2 in the lung.
33372574 ), and one human cellular transmembrane serine proteinase (TMPRSS2), was carried out.
33375616 The human serine protease serine 2 TMPRSS2 is involved in the priming of proteins of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and represents a possible target for COVID-19 therapy. […] The TMPRSS2 gene may be co-expressed with SARS-CoV-2 cell receptor genes angiotensin-converting enzyme 2 (ACE2) and Basigin (BSG), but only TMPRSS2 demonstrates tissue-specific expression in alveolar cells according to single-cell RNA sequencing data. […] Our analysis of the structural variability of the TMPRSS2 gene based on genome-wide data from 76 human populations demonstrates that a functionally significant missense mutation in exon 6/7 in the TMPRSS2 gene is found in many human populations at relatively high frequencies, with region-specific distribution patterns. […] In addition to single-nucleotide polymorphisms, two copy number variants were detected in the TMPRSS2 gene. […] A number of microRNAs have been predicted to regulate TMPRSS2 and BSG expression levels, but none of them is enriched in lung or respiratory tract cells. […] Several well-studied drugs can downregulate the expression of TMPRSS2 in human cells, including acetaminophen (paracetamol) and curcumin. […] Thus, the interactions of TMPRSS2 with SARS-CoV-2, together with its structural variability, gene-gene interactions, expression regulation profiles, and pharmacogenomic properties, characterize this gene as a potential target for COVID-19 therapy.
33380375 Thus, we have proposed two novel drug targets, Furin and TMPRSS2, as Covid-19 treatment strategy. […] STUDY DESIGN & METHODS: An earlier study suggested that Furin and TMPRSS2 knockout mice had reduced level of viral load and a lower degree of organ damage such as the lung. […] The present study thus highlights the promise of some selected novel and potential anti-viral Phytopharmaceutical that bind to Furin and TMPRSS2 as target. […] Hence, this strategy may limit life-threatening Covid-19 infection and its mortality rate through nano-suspension based intra-nasal or oral nebulizer spray, to treat mild to moderate SARS-COV-2 infection when Furin and TMPRSS2 receptor may initiate to express and activate for processing the virus to cause cellular infection by replication within the host cell and blocking of host-viral interaction.
33382023 TMPRSS2 is gateway for SARS CoV-2 entry into the host cell. […] The TMPRSS2 inhibition could be one of the approaches to stop the viral entry, therefore, interaction pattern and binding energies for Fisetin and TMPRSS2 have been explored in the present study. […] TMPRSS2 peptide was used for homology modelling and then for further study. […] Molecular docking score and MMGBSA Binding energy of Fisetin was better than Nafamostat, a known inhibitor of TMPRSS2. […] RMSD plots of TMPRSS2, TMPRSS2-Fisetin and TMPRSS2-Nafamostat complex showed stable profile with very small fluctuation during entire simulation of 150 ns. […] Significant decrease in TMPRSS2-Fisetin and TMPRSS2-Nafamostat complex fluctuation occurred around His 41, Glu 44, Gly 136, Ser 186 in RMSF study. […] Post simulation MM-GBSA free energy was found to be -51.87 ± 4.3 and -48.23 ± 4.39 kcal/mol for TMPRSS2 with Fisetin and Nafamostat, respectively.
33388025 On one hand, this is attributable to the fact that T may facilitate SARS-CoV-2 entry in human cells by means of an enhanced expression of transmembrane serine-protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2).
33390952 In addition, theaflavin-3-gallate could inhibit protein expression of ACE2 and TMPRSS2 without significant cytotoxicity. […] Our results suggest that GB-1 and theaflavin-3-gallate could act as potential candidates for prophylaxis or treatment of SARS-CoV-2 infection through inhibiting protein expression of ACE2 and TMPRSS2 for the further study.
33390974 failure due to failure to achieve adequate drug concentration at the target site and attenuation of its inhibitory effect due to the presence of TMPRSS2 in airway epithelial cells.
33391014 This function is similar to that of TMPRSS2, which underpins the entry of viruses into the host cell.
33391636 SARS-CoV-2 entry is mediated by binding of the spike protein (S) to the surface receptor ACE2 and subsequent priming by host TMPRSS2 allowing membrane fusion. […] Reduction of infectivity positively correlates with the level of ACE2, is much more efficient than with soluble ACE2 and further enhanced by the inclusion of TMPRSS2.
33391931 The receptor for SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2), as well as the necessary protease to facilitate viral entry, transmembrane protease serine-2 (TMPRSS2), and to a lesser extent, cathepsins, have been demonstrated to be present throughout the gastrointestinal tract, thus facilitating viral entry and pathogenesis.
33394891 SARS-CoV-2 enters host cells via angiotensin converting enzyme-2 (ACE2) and the serine protease TMPRSS2. […] We analyzed tissue ACE2 and TMPRSS2 gene expression in pediatric eosinophilic esophagitis (EoE), eosinophilic gastritis (EG) and in normal adult esophagi using publicly available RNA sequencing datasets. […] Similar to findings evaluating the airway, there was no difference in tissue ACE2/TMPRSS2 expression in EoE or EG when compared to control non-EoE/EG esophagus/stomach.
33397514 Interestingly, serine protease transmembrane serine protease 2 (TMPRSS2) had less expression in cardiomyocytes, but CTSB and CTSL, which belonged to cell protease, could be found to be enriched in cardiomyocytes.
33401565 Moreover, we sought to understand the interplay of type I interferon (IFN-I) with ACE2, furin and TMPRSS2 by evaluating their gene expression with respect to ISG15, a well-known marker of IFN activation, in upper respiratory samples and after ex vivo IFNβ exposure. […] Lower ACE2 levels and trends toward the reduction of furin and TMPRSS2 were found in CF patients compared with the healthy controls; decreased ACE2 amounts were also detected in CF individuals with pancreatic insufficiency and in those receiving inhaled antibiotics.
33401657 Angiotensin-converting enzyme II (ACE2) is the receptor protein of SARS-CoV-2, and TMPRSS2 promotes virus proliferation and transmission. […] We investigated the ACE2 and TMPRSS2 expression levels of cell types from 31 organs to evaluate the risk of viral infection using single-cell RNA sequencing (scRNA-seq) data. […] Besides, the nose, heart, small intestine, large intestine, esophagus, brain, testis, and kidney are also identified to be high-risk organs with high expression levels of ACE2 and TMPRSS2. […] Moreover, the susceptible organs are grouped into three risk levels based on the ACE2 and TMPRSS2 expression.
33405098 Successful entry of SARS-CoV-2 into the body is dependent on the angiotensin-converting enzyme 2 (ACE2) receptor and the transmembrane protease serine 2 (TMPRSS2). […] Thus, sex-based differences in the expression of the ACE2 receptor and TMPRSS2 may explain the disparities in COVID-19 severity and fatality.
33407110 The virus uses ACE2 and TMPRSS2 as key viral entry associated proteins expressed in human cells for infections.
33409413 ) inhibitors of host transmembrane protease serine 2 (TMPRSS2), endosomal trafficking, and pyrimidine synthesis.
33412255 We discuss how the virus may use established infection mechanisms (ACE2, TMPRSS2, and Cathepsin L), as well mechanisms still under consideration (NRP1 and BASIGIN) to infect and spread throughout the CNS.
33413387 Angiotensin converting enzyme-2 (ACE2) and the enzyme proteases, transmembrane protease serine 2 (TMPRSS2) and FURIN, are needed for viral attachment and invasion into host cells. […] We examined microarray mRNA expression of ACE2, TMPRSS2 and FURIN in sputum, bronchial brushing and bronchial biopsies of the European U-BIOPRED cohort. […] In bronchial brushing samples, TMPRSS2 levels were positively associated with male gender and body mass index, whereas FURIN levels with male gender and blood neutrophils. […] In bronchial biopsies, TMPRSS2 levels were positively related to blood neutrophils.
33419885 IAV also increased the expression of two proteases known to cleave ACE2, sheddase ADAM17 (TACE) and TMPRSS2 and increased the TMPRSS2 zymogen and its mature fragments, implicating proteolytic autoactivation.
33421967 The distribution of cells expressing SARS-CoV-2 entry factor angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) in human oral tissues were tested. […] The ACE2 and TMPRSS2 expression was detected with all subjects in the normal mucosa of the keratinized stratified squamous epithelia of the tongue and non-keratinized stratified squamous epithelia of the lip and cheek. […] It was found that ACE2 is expressed in the cytoplasm and on the cell membrane mainly in the stratum granulosum of the epithelia while the TMPRSS2 is strongly expressed on the cell membrane mainly in the stratum granulosum and stratum spinosum, but not in the stratum basale. […] Antibodies’ reactions for ACE2 and TMPRSS2 were not observed in the nuclei or keratin layer. […] The expression of ACE2 and TMPRSS2 in the oral epithelia appears to be general, and the expression was also observed in the mucous and serous acini of the labial glands.
33421977 This study aimed to examine the expressions of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) in tumor tissues of six common cancer types. […] The expression levels of ACE2 and TMPRSS2 in tumors and control samples were obtained from online databases. […] There was the overexpression of ACE2 in colon and stomach adenocarcinomas compared to controls, meanwhile colon and prostate adenocarcinomas showed a significantly higher expression of TMPRSS2. […] Additionally, survival prognosis analysis has demonstrated that upregulation of ACE2 in liver hepatocellular carcinoma was associated with higher overall survival (hazard ratio=0.65, p=0.016) and disease-free survival (hazard ratio=0.66, p=0.007), while overexpression of TMPRSS2 was associated with a 26% reduced risk of death in lung adenocarcinoma (p=0.047) but 50% increased risk of death in breast invasive carcinoma (p=0.015).
33422505 In this study, we used a mouse model exposed to crude PM, collected by the cyclone method, to evaluate the pulmonary expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine type 2 (TMPRSS2), the two molecules required for the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into host cells.
33422990 All anatomical regions were immunohistochemically tested for ACE2, TMPRSS2, CD147, CD45, CD3, CD4, CD8, CD68 and IL-6. […] COVID-19 positive patients showed strong ACE2 / TMPRSS2 expression in capillaries and less in arterioles/venules. […] ACE2 / TMPRSS2 expression and lymphomonocytic inflammation in COVID-19 disease increases crescentically towards the small vessels suggesting that COVID-19-induced endotheliitis is a small vessel vasculitis not involving the main coronaries.
33425965 SARS-CoV-2 enters into human airway epithelial cells via membrane fusion or endocytosis, and this process is dependent on ACE2, TMPRSS2, and cathepsin L. […] This study revealed that (i) cigarette smoking is associated with an increased expression of ACE2 and TMPRSS2 and a decreased expression of cathepsin L; (ii) significant alternations in expression of ACE2, TMPRSS2, and cathepsin L were observed between current smokers and former smokers, but not between former smokers and never smokers; (iii) when compared with healthy controls with identical smoking status, patients with COPD or lung cancer showed negligible changes in expression of ACE2, TMPRSS2, and cathepsin L.
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.
33439572 The coronavirus S protein mediates viral entry into target cells employing the host cellular serine protease TMPRSS2 for S-protein priming. […] The TMPRSS2 gene expression is responsive to androgen stimulation and it could partially explain sex differences.
33447763 The transcriptomic analysis revealed a significant increase of ACE2 and TMPRSS2 in the blood of patients with hypertension. […] Some of these medications increased TMPRSS2, while others, like furosemide, significantly reduced COVID-19 receptors. […] Treatment of common co-morbidities often require chronic use of multiple medications, which may result in an additive increase in the expression of ACE2 and TMPRSS2.
33450625 Transmembrane protease serine 2 (TMPRSS2) has been found to be critical in priming the viral spike protein and the host ACE2 receptor before the virus enters into the host cell. […] Recent studies have experimentally demonstrated that Alpha 1 antitrypsin (encoded by SERPINA1 gene) is an inhibitor of TMPRSS2 and provided support to the already approved therapy as a candidate for COVID-19. […] Here we have provided in silico evidence that Alpha 1 antitrypsin can interact with TMPRSS2 and both of them are co-expressed in the human liver and lung.
33452303 Here, the effect of ACE2 variations by focusing on the receptor-binding site of SARS-CoV-2 and ACE2 cleavage by TMPRSS2 protease were investigated through simulations study. […] Moreover, our bioinformatics simulation of 3D structures and docking of proteins explains important details of ACE2-Spike and ACE2-TMPRSS2 interactions, especially the critical role of Arg652 of ACE2 for protease function of TMPRSS2 was uncovered.
33463909 Afterward, we found that SARS-CoV-2 infection per se results in ACE2 and TMPRSS2 increased gene expression in VERO E6-cell, which could be generating a cycle of virus infection in host cells. […] The estrogen treatment reduces the levels of the TMPRSS2, which are involved with SARS-CoV-2 infectiveness capacity, and hence, reducing the pathogenicity/genesis.
33465165 The plasma membrane-associated protease TMPRSS2 can similarly cleave these S proteins and activate viral entry at the cell surface. […] Here we show that the SARS-CoV-2 entry process is more dependent than that of SARS-CoV-1 on TMPRSS2 expression. […] We also show that hydroxychloroquine efficiently blocks viral entry mediated by cathepsin L, but not by TMPRSS2, and that a combination of hydroxychloroquine and a clinically-tested TMPRSS2 inhibitor prevents SARS-CoV-2 infection more potently than either drug alone.
33466589 Infiltration and spread of SARS-CoV-2 are based on the interaction between the virus’ structural protein S and the cell’s receptor-angiotensin-converting enzyme 2 (ACE2), with the simultaneous involvement of human trans-membrane protease, serine 2 (TMPRSS2).
33476327 These alterations were shown to result from their inability to utilize the entry pathway involving direct fusion mediated by the host type II transmembrane serine protease, TMPRSS2. […] Notably, viruses with S gene mutations emerged rapidly and became the dominant SARS-CoV-2 variants in TMPRSS2-deficient cells including Vero cells.
33477294 It has been proposed that spironolactone may prevent acute lung injury in COVID-19 infection due to its pleiotropic effects with favorable renin-angiotensin-aldosterone system (RAAS) and ACE2 expression, reduction in transmembrane serine protease 2 (TMPRSS2) activity and antiandrogenic action, and therefore it may prove to act as additional protection for patients at highest risk of severe pneumonia.
33479353 Our analysis suggests that at the infection stage DS individuals might be more susceptible to infection due to triplication of TMPRSS2, that primes the viral S protein for entry in the host cells.
33479506 Little is known of the patterns of expression of ACE2 and TMPRSS2 or the clinical characteristics of COVID-19 in patients with COVID-19 and colorectal cancer. […] We found in both bulk and single-cell RNA-seq profiles that ACE2 and TMPRSS2 were expressed at high levels on tumor and normal colorectal epithelial tissues.
33484868 Further, the severity of COVID-19 is greatly enhanced in lung cancer patients, probably due to the genes such as ACE2, TMPRSS2, PAI-1 and furin that are commonly involved in cancer progression as well as SAR-CoV-2 infection.
33486379 FURIN was positively regulated in some cases, such as leukemia, psoriasis, NAFLD, lung cancer, and type II diabetes (T2D), while TMPRSS2 was positively regulated in only 3 cases, namely, leukemia, lung cancer, and T2D.
33486479 Virus-cell fusion is mediated by angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) with their organ expression pattern determining viral tropism. […] Here, we provide a comprehensive expression landscape of ACE2 and TMPRSS2 proteins across human postmortem nasal and olfactory tissue. […] Vice versa, TMPRSS2 can also be detected in the sustentacular cells and the glandular cells of the olfactory epithelium. […] Our findings provide the basic anatomical evidence for the expression of ACE2 and TMPRSS2 in the human nose, olfactory epithelium, and olfactory bulb.
33488517 ACE2 and TMPRSS2 expression was examined in human adrenal glands by immunohistochemical staining. […] ACE2 receptor and TMPRSS2 serine protease were colocalized in adrenocortical cells in zona fasciculata and zona reticularis. […] We demonstrate that ACE2 and TMPRSS2 are colocalized in adrenocortical cells, and that the cortisol levels are lower in critically ill patients with COVID-19 as compared to those of non-COVID-19 critically ill patients.
33493182 Fusion is triggered by the protease TMPRSS2, which processes the viral Spike (S) protein to reveal the fusion peptide. […] SARS-CoV-2 has evolved a multibasic site at the S1-S2 boundary, which is thought to be cleaved by furin in order to prime S protein for TMPRSS2 processing. […] We show that loss of furin in either donor or acceptor cells reduces, but does not prevent, TMPRSS2-dependent cell-cell fusion, unlike mutation of the multibasic site that completely prevents syncytia formation.
33497931 We performed a retrospective comparative immunohistochemical, immunofluorescence and Western blot analysis of ACE2, TMPRSS2 and Cathepsin B expression in anemic and polycythemic territories of TAPS placentas (N = 14). […] ACE2 protein levels were significantly higher in the anemic twin territories than in the corresponding polycythemic territories, associated with upregulation of the key ACE2-related cell entry regulators, TMPRSS2 and Cathepsin B, immunolocalized to villous trophoblastic and stromal cells. […] Cellular colocalization of ACE2 and TMPRSS2, suggestive of functionality of this cell entry axis, was demonstrated by double immunofluorescence studies.
33505639 Recent studies showed that two drugs, Camostat and Nafamostat, might be repurposed to treat COVID-19 by inhibiting human TMPRSS2 required for proteolytic activation of viral spike (S) glycoprotein. […] Here, we perform molecular dynamics simulations to investigate their native binding sites on TMPRSS2. […] We revealed that both drugs could spontaneously and stably bind to the TMPRSS2 catalytic center, and thereby inhibit its proteolytic processing of the S protein.
33507952 The host protease TMPRSS2 was required for infection of these cells.
33512650 Several drug targets have been reported to inhibit the SARS-CoV-2 virus infection, in that TMPRSS2 (transmembrane protease serine 2) is one of the potential targets; inhibiting this protease stops the virus entry into the host human cell. […] To consider these drugs as the repurposed drug for COVID-19, it is essential to understand their binding affinity and stability with TMPRSS2. […] In the present study, we performed the molecular docking and molecular dynamics (MD) simulation of these molecules with the TMPRSS2. […] The docking study reveals that leupeptin molecule strongly binds with TMPRSS2 protein than the other two drug molecules. […] The RMSD and RMSF values of MD simulation confirm that leupeptin and the amino acids of TMPRSS2 are very stable than the other two molecules. […] Furthermore, leupeptin forms interactions with the key amino acids of TMPRSS2 and the same have been maintained during the MD simulations. […] This structural and dynamical information is useful to evaluate these drugs to be used as repurposed drugs, however, the strong binding profile of leupeptin with TMPRSS2, suggests, it may be considered as a repurposed drug for COVID-19 disease after clinical trial.
33513400 CHEMICAL COMPOUNDS: Angiotensin-converting enzyme 2 (ACE2); atrial natriuretic peptide (ANP); cathepsin L; heparan sulphate proteoglycans (HSPGs); interferon; interleukin; oxytocin; superoxide dismutase; transmembrane serine protease isoform 2 (TMPRSS2).
33521067 We present results of our optimization of the system to enhance viral infection levels through the over-expression of human ACE2 receptor and the overexpression of at least one of two proteases - TMPRSS2 or Furin, as well as, supplementation with Poloxamer 407 (P407) and Prostaglandin E2 (PGE2) as adjuvants.
33521687 To study mRNA and protein expression of SARS-CoV-2 entry receptors (ACE2, CD147) and proteases (TMPRSS2, CTSL) in human oocytes, embryos, cumulus and granulosa cells. […] The presence or absence of ACE2, CD147, TMPRSS2, and CTSL mRNA using RT-qPCR and protein using capillary Western blotting in human oocytes, embryos and ovarian follicular cells. […] TMPRSS2 protein was present in all samples while mRNA was observed only at the blastocyst stage. […] Cumulus and granulosa cells are least susceptible to SARS-CoV-2 infection due to the lack of required receptors and proteases combination (ACE2/TMPRSS2 or CD147/CTSL) in high abundance. […] Co-expression of the ACE2 and TMPRSS2 proteins in MII oocytes, zygotes, and blastocysts demonstrate that these gametes and embryos have the cellular machinery required and thus are potentially susceptible to SARS-CoV-2 infection if exposed to the virus.
33522308 TMPRSS2 is essential for COVID-19 replication cycle and it is under androgen control. […] Estrogen and androgen receptor dependent cues converge on TMPRSS2 regulation through different mechanisms of action that can be blocked by the use of hormonal therapies. […] Androgen receptor (AR) signaling in the transmembrane protease serine 2 (TMPRSS2) regulation is emerging as an important determinant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) susceptibility. […] In our study, we analyzed AR and TMPRSS2 expression in 17,352 normal and 9,556 cancer tissues from public repositories and stratified data according to sex and age.
33524396 Here, we produced six mouse anti-SARS-CoV-2 spike monoclonal antibodies that exhibit not only robust performance in immunoassays including western blotting, ELISA, immunofluorescence, and immunoprecipitation, but also demonstrate neutralizing activity against SARS-CoV-2 infection to VeroE6/TMPRSS2 cells.
33525682 To validate the potential entry of SARS-CoV-2 infection in the retina, we showed that hiPSC-derived retinal organoids and monolayer cultures endogenously express ACE2 and transmembrane serine protease 2 (TMPRSS2) on the mRNA level. […] Immunofluorescence staining confirmed the protein expression of ACE2 and TMPRSS2 in retinal organoids and monolayer cultures.
33526471 Human kidney organoids express ACE2 and TMPRSS2, and when infected with SARS-CoV-2, our modified long-acting ACE2 variant neutralized infection.
33531686 This Comment explores the interaction between COVID-19 and cancer with attention paid to the modulation by cancer treatments of both ADAM17 and TMPRSS2, the proteases which control ACE2 processing, the SARS-CoV-2 target.
33539819 As there is no specific drug treatment available for COVID-19 pandemic, we explored in silico repurposing of drugs with dual inhibition properties by targeting transmembrane serine protease 2 (TMPRSS2) and human angiotensin-converting enzyme 2 (ACE2) from FDA-approved drugs. […] The TMPRSS2 and ACE2 dual inhibitors in COVID-19 would be a novel antiviral class of drugs called “entry inhibitors.” […] For this purpose, approximately 2800 US-FDA approved drugs were docked using a virtual docking tool with the targets TMPRSS2 and ACE2.
33550034 Choosing an ideal in-vitro model is vital as the virus entry is through ACE2, CD147, and TMPRSS2 dependant and very specific.
33552835 Such drugs comprise of inhibitors of Angiotensin-Converting Enzyme 2 (ACE2), transmembrane Serine Protease 2 (TMPRSS2), nonstructural protein 3C-like protease, nonstructural RNA-dependent RNA polymerase (RdRp) and many more.
33556379 RA-differentiation induced an upregulation of ace2 and tmprss2 gene expression while inducing downregulation of ctsb and ctsl.
33557330 SARS-CoV-2 infection begins by attaching to angiotensin-converting enzyme 2 receptor (ACE2) via the spike glycoprotein, followed by cleavage by TMPRSS2, revealing the viral fusion domain.
33558493 Such mutations can occur in the spike (S) protein that binds to the ACE2 receptor and is cleaved by TMPRSS2. […] Here, we show that naturally occurring S mutations can reduce or enhance cell entry via ACE2 and TMPRSS2.
33558541 Among these drugs, a second-generation antiandrogen agent, enzalutamide, was proposed because it reduces the expression of transmembrane serine protease 2 (TMPRSS2), a key component mediating SARS-CoV-2-driven entry, in prostate cancer cells. […] Tmprss2 knockout significantly inhibited SARS-CoV-2 infection in vivo. […] Accordingly, enzalutamide showed no antiviral activity due to the AR-independent TMPRSS2 expression in mouse and human lung epithelial cells. […] Moreover, we observed distinct AR binding patterns between prostate cells and lung cells and a lack of direct binding of AR to TMPRSS2 regulatory locus in human lung cells. […] Thus, our findings do not support the postulated protective role of enzalutamide in treating COVID-19 through reducing TMPRSS2 expression in lung cells.
33558851 Viral entry requires ACE2 and transmembrane protease serine 2 (TMPRSS2) for membrane fusion or through endosomal pathway. […] Also, no significant change was observed in expression levels of ACE2 or TMPRSS2 in response to SARS CoV-2 infection.
33558864 While ACE2 receptor is found in reproductive organs, the lack of co-expression of the TMPRSS2 modulatory protein, required for SARS-CoV-2 cell entry, in testicular cells, sperm, or oocytes, argues against the hypothesis that gametes transmit SARS-CoV-2.
33559937 ACE2 and TMPRSS2, which play a critical role in the entrance of SARS-COV-2 into the cell, are coexpressed in placental development stages, so the placenta also carries a risk for this virus.
33560365 Variations in the S protein (mediates virus entry) were associated with differences in its interaction with ACE2 (cellular S receptor) and sensitivity to TMPRSS2 (enables virus entry via S cleavage) inhibition. […] Cellular ACE2 and TMPRSS2 levels did not indicate susceptibility to SARS-CoV-2.
33561380 One nasal and one mouth spray suppressed SARS-CoV-2 infection of TMPRSS2-Vero E6 cells and primary differentiated human airway epithelial cultures.
33563156 In this work two home-made databases from synthetic quinolines and coumarins were virtually docked against viral proteases (3CL and PL), human cell surface proteases (TMPRSS2 and furin) and spike proteins (S1 and S2). […] Two compounds, quinoline-1 and coumarin-24, were found to be effective on three targets - S2, TMPRSS2 and furin - simultaneously, with good predicted affinity between -7.54 to -8.85 kcal/mol.
33564056 In this study, we investigated the variability of four genes (ACE2, ANPEP and DPP4 encoding for host receptors of the viral spike proteins and TMPRSS2 encoding for a host proteinase) in 23 European (19 autochthonous and three commercial breeds and one wild boar population) and two Asian Sus scrofa populations.
33564221 Based on structural data derived from X-ray crystallographic data of related trypsin-like proteases, a homology model of TMPRSS2 is described and validated using the broad spectrum COVID-19 drug candidate camostat as a probe. […] Based on the binding mode of GBPA, residues K342 and W461 have been identified as potential contacts involved in TMPRSS2 selective binding and activity. […] Taken overall, the proposed structure along with the key contact sites and mechanistic features identified should prove highly advantageous to the design and rational development of safe and effective therapeutics that target TMPRSS2 and avoid inhibition of other trypsin-dependent processes.
33566370 Likewise, these interventions had no effect on the expression of Transmembrane Protease Serine 2 (TMPRSS2) and Furin, proteases that facilitate the virus-cell fusion, and the expression or activity of Tumor Necrosis Factor α-Convertase (TACE) that cleaves cell-surface ACE2.
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. […] Besides drugs in clinical trend, TMPRSS2 inhibitors, estrogen supplementation, androgen deprivation and DPP-IV inhibitors may also be used to treat breast cancer patients infected with SARS-CoV-2.