Review Article

Can Host Cell Proteins Like ACE2, ADAM17, TMPRSS2, Androgen Receptor be the Efficient Targets in SARS-CoV-2 Infection?

Author(s): Vivek K. Gupta*, Madhan K. Murthy and Shripad Patil

Volume 22, Issue 10, 2021

Published on: 25 November, 2020

Page: [1149 - 1157] Pages: 9

DOI: 10.2174/1389450121999201125201112

Price: $65

Abstract

A novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV- -2), which caused a large disease outbreak in Wuhan, China in December 2019, is currently spreading across the world. Along with binding of the virus spike with the host cell receptor, fusion of the viral envelope with host cell membranes is a critical step in establishing successful infection of SARS-CoV-2. In this entry process, a diversity of host cell proteases and androgen receptor play a very important role directly or indirectly. These features of SARS-CoV-2 entry contribute to its rapid spread and severe symptoms, high fatality rates among infected patients.

This review is based on the latest published literature including review articles, research articles, hypothetical manuscript, preprint articles and official documents. The literature search was made from various published papers on physiological aspects relevant to SARS-CoV and SARS-CoV-2.

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. We have also summarized how these host proteins increase the pathology and the infective ability of SARS-CoV-2 and we posit that their inhibition may be a therapeutic option for preventing SARS-CoV-2 infection.

Keywords: SARS-CoV-2, COVID-19, ACE2, ADAM17, TMPRSS2, Androgen receptor, anti-viral drugs.

Graphical Abstract

[1]
Lu R, Zhao X, Li J, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 2020; 395(10224): 565-74.
[http://dx.doi.org/10.1016/S0140-6736(20)30251-8] [PMID: 32007145]
[2]
WHO Coronavirus Disease (COVID-19) Dashboard. 2020.https://covid19.who.int/
[3]
Shang J, Wan Y, Luo C, et al. Cell entry mechanisms of SARS-CoV-2. Proc Natl Acad Sci USA 2020; 117(21): 11727-34.
[http://dx.doi.org/10.1073/pnas.2003138117] [PMID: 32376634]
[4]
Li W, Moore MJ, Vasilieva N, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 2003; 426(6965): 450-4.
[http://dx.doi.org/10.1038/nature02145] [PMID: 14647384]
[5]
Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020; 181(2): 271-280.e8.
[http://dx.doi.org/10.1016/j.cell.2020.02.052] [PMID: 32142651]
[6]
Wu D, Wu T, Liu Q, Yang Z. The SARS-CoV-2 outbreak: What we know. Int J Infect Dis 2020; 94: 44-8.
[http://dx.doi.org/10.1016/j.ijid.2020.03.004] [PMID: 32171952]
[7]
Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor recognition by the novel coronavirus from wuhan: an analysis based on decade-long structural studies of SARS Coronavirus. J Virol 2020; 94(7): e00127-20.
[http://dx.doi.org/10.1128/JVI.00127-20] [PMID: 31996437]
[8]
Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic Treatments for coronavirus disease 2019 (COVID-19): A Review. JAMA 2020; 323(18): 1824-36.
[http://dx.doi.org/10.1001/jama.2020.6019] [PMID: 32282022]
[9]
Yousefi B, Valizadeh S, Ghaffari H, Vahedi A, Karbalaei M, Eslami M. A global treatments for coronaviruses including COVID-19. J Cell Physiol 2020; 235(12): 9133-42.
[http://dx.doi.org/10.1002/jcp.29785] [PMID: 32394467]
[10]
Tu YF, Chien CS, Yarmishyn AA, et al. A Review of SARS-CoV-2 and the ongoing clinical trials. Int J Mol Sci 2020; 21(7): 2657.
[http://dx.doi.org/10.3390/ijms21072657] [PMID: 32290293]
[11]
Du L, He Y, Zhou Y, Liu S, Zheng BJ, Jiang S. The spike protein of SARS-CoV--a target for vaccine and therapeutic development. Nat Rev Microbiol 2009; 7(3): 226-36.
[http://dx.doi.org/10.1038/nrmicro2090] [PMID: 19198616]
[12]
Burrell LM, Johnston CI, Tikellis C, Cooper ME. ACE2, a new regulator of the renin-angiotensin system. Trends Endocrinol Metab 2004; 15(4): 166-9.
[http://dx.doi.org/10.1016/j.tem.2004.03.001] [PMID: 15109615]
[13]
Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020; 579(7798): 270-3.
[http://dx.doi.org/10.1038/s41586-020-2012-7] [PMID: 32015507]
[14]
Jia HP, Look DC, Tan P, et al. Ectodomain shedding of angiotensin converting enzyme 2 in human airway epithelia. Am J Physiol Lung Cell Mol Physiol 2009; 297(1): L84-96.
[http://dx.doi.org/10.1152/ajplung.00071.2009] [PMID: 19411314]
[15]
Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol 2004; 203(2): 631-7.
[http://dx.doi.org/10.1002/path.1570] [PMID: 15141377]
[16]
Sims AC, Baric RS, Yount B, Burkett SE, Collins PL, Pickles RJ. Severe acute respiratory syndrome coronavirus infection of human ciliated airway epithelia: role of ciliated cells in viral spread in the conducting airways of the lungs. J Virol 2005; 79(24): 15511-24.
[http://dx.doi.org/10.1128/JVI.79.24.15511-15524.2005] [PMID: 16306622]
[17]
Jia HP, Look DC, Shi L, et al. ACE2 receptor expression and severe acute respiratory syndrome coronavirus infection depend on differentiation of human airway epithelia. J Virol 2005; 79(23): 14614-21.
[http://dx.doi.org/10.1128/JVI.79.23.14614-14621.2005] [PMID: 16282461]
[18]
Li F, Li W, Farzan M, Harrison SC. Structure of SARS coronavirus spike receptor-binding domain complexed with receptor. Science 2005; 309(5742): 1864-8.
[http://dx.doi.org/10.1126/science.1116480] [PMID: 16166518]
[19]
Wang X, Dhindsa R, Povysil G, et al. Transcriptional inhibition of host viral entry proteins as a therapeutic strategy for SARS-CoV-2. Preprints 2020; 2020030360
[http://dx.doi.org/10.20944/preprints202003.0360.v1]
[20]
Tai W, He L, Zhang X, et al. Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine. Cell Mol Immunol 2020; 17(6): 613-20.
[http://dx.doi.org/10.1038/s41423-020-0400-4] [PMID: 32203189]
[21]
Haga S, Yamamoto N, Nakai-Murakami C, et al. Modulation of TNF-alpha-converting enzyme by the spike protein of SARS-CoV and ACE2 induces TNF-alpha production and facilitates viral entry. Proc Natl Acad Sci USA 2008; 105(22): 7809-14.
[http://dx.doi.org/10.1073/pnas.0711241105] [PMID: 18490652]
[22]
Imai Y, Kuba K, Rao S, et al. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature 2005; 436(7047): 112-6.
[http://dx.doi.org/10.1038/nature03712] [PMID: 16001071]
[23]
Kuba K, Imai Y, Rao S, et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med 2005; 11(8): 875-9.
[http://dx.doi.org/10.1038/nm1267] [PMID: 16007097]
[24]
Glowacka I, Bertram S, Herzog P, et al. Differential downregulation of ACE2 by the spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus NL63. J Virol 2010; 84(2): 1198-205.
[http://dx.doi.org/10.1128/JVI.01248-09] [PMID: 19864379]
[25]
Pinto BGG, Oliveira AER, Singh Y, et al. ACE2 expression is increased in the lungs of patients with comorbidities associated with severe COVID-19. J Infect Dis 2020; 222(4): 556-63.
[http://dx.doi.org/10.1093/infdis/jiaa332] [PMID: 32526012]
[26]
Ferrario CM, Jessup J, Chappell MC, et al. Effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockers on cardiac angiotensin-converting enzyme 2. Circulation 2005; 111(20): 2605-10.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.104.510461] [PMID: 15897343]
[27]
Kai H, Kai M. Interactions of coronaviruses with ACE2, angiotensin II, and RAS inhibitors-lessons from available evidence and insights into COVID-19. Hypertens Res 2020; 43(7): 648-54.
[http://dx.doi.org/10.1038/s41440-020-0455-8] [PMID: 32341442]
[28]
Diaz JH. Hypothesis: angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may increase the risk of severe COVID-19. J Travel Med 2020; 27(3)
[29]
Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med 2020; 8(4): e21.
[http://dx.doi.org/10.1016/S2213-2600(20)30116-8] [PMID: 32171062]
[30]
Esler M, Esler D. Can angiotensin receptor-blocking drugs perhaps be harmful in the COVID-19 pandemic? J Hypertens 2020; 38(5): 781-2.
[http://dx.doi.org/10.1097/HJH.0000000000002450] [PMID: 32195824]
[31]
Bavishi C, Maddox TM, Messerli FH. Coronavirus Disease 2019 (COVID-19) infection and renin angiotensin system blockers. JAMA Cardiol 2020; 5(7): 745-7.
[http://dx.doi.org/10.1001/jamacardio.2020.1282] [PMID: 32242890]
[32]
Vaduganathan M, Vardeny O, Michel T, McMurray JJV, Pfeffer MA, Solomon SD. Renin-angiotensin-aldosterone system inhibitors in patients with Covid-19. N Engl J Med 2020; 382(17): 1653-9.
[http://dx.doi.org/10.1056/NEJMsr2005760] [PMID: 32227760]
[33]
Chung MK, Karnik S, Saef J, et al. SARS-CoV-2 and ACE2: The biology and clinical data settling the ARB and ACEI controversy. EBioMedicine 2020; 58: 102907.
[http://dx.doi.org/10.1016/j.ebiom.2020.102907] [PMID: 32771682]
[34]
Soler MJ, Wysocki J, Ye M, Lloveras J, Kanwar Y, Batlle D. ACE2 inhibition worsens glomerular injury in association with increased ACE expression in streptozotocin-induced diabetic mice. Kidney Int 2007; 72(5): 614-23.
[http://dx.doi.org/10.1038/sj.ki.5002373] [PMID: 17579661]
[35]
Jin HY, Chen LJ, Zhang ZZ, et al. Deletion of angiotensin-converting enzyme 2 exacerbates renal inflammation and injury in apolipoprotein E-deficient mice through modulation of the nephrin and TNF-alpha-TNFRSF1A signaling. J Transl Med 2015; 13: 255.
[http://dx.doi.org/10.1186/s12967-015-0616-8] [PMID: 26245758]
[36]
Lambert DW, Yarski M, Warner FJ, et al. Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensin-converting enzyme-2 (ACE2). J Biol Chem 2005; 280(34): 30113-9.
[http://dx.doi.org/10.1074/jbc.M505111200] [PMID: 15983030]
[37]
Gooz M. ADAM-17: the enzyme that does it all. Crit Rev Biochem Mol Biol 2010; 45(2): 146-69.
[http://dx.doi.org/10.3109/10409231003628015] [PMID: 20184396]
[38]
Ortiz-Pérez JT, Riera M, Bosch X, et al. Role of circulating angiotensin converting enzyme 2 in left ventricular remodeling following myocardial infarction: a prospective controlled study. PLoS One 2013; 8(4): e61695.
[http://dx.doi.org/10.1371/journal.pone.0061695] [PMID: 23630610]
[39]
Ramchand J, Patel SK, Srivastava PM, Farouque O, Burrell LM. Elevated plasma angiotensin converting enzyme 2 activity is an independent predictor of major adverse cardiac events in patients with obstructive coronary artery disease. PLoS One 2018; 13(6): e0198144.
[http://dx.doi.org/10.1371/journal.pone.0198144] [PMID: 29897923]
[40]
Xia H, Sriramula S, Chhabra KH, Lazartigues E. Brain angiotensin-converting enzyme type 2 shedding contributes to the development of neurogenic hypertension. Circ Res 2013; 113(9): 1087-96.
[http://dx.doi.org/10.1161/CIRCRESAHA.113.301811] [PMID: 24014829]
[41]
Walters TE, Kalman JM, Patel SK, Mearns M, Velkoska E, Burrell LM. Angiotensin converting enzyme 2 activity and human atrial fibrillation: increased plasma angiotensin converting enzyme 2 activity is associated with atrial fibrillation and more advanced left atrial structural remodelling. Europace 2017; 19(8): 1280-7.
[http://dx.doi.org/10.1093/europace/euw246] [PMID: 27738071]
[42]
Epelman S, Shrestha K, Troughton RW, et al. Soluble angiotensin-converting enzyme 2 in human heart failure: relation with myocardial function and clinical outcomes. J Card Fail 2009; 15(7): 565-71.
[http://dx.doi.org/10.1016/j.cardfail.2009.01.014] [PMID: 19700132]
[43]
Gelling RW, Yan W, Al-Noori S, et al. Deficiency of TNFalpha converting enzyme (TACE/ADAM17) causes a lean, hypermetabolic phenotype in mice. Endocrinology 2008; 149(12): 6053-64.
[http://dx.doi.org/10.1210/en.2008-0775] [PMID: 18687778]
[44]
Xu J, Mukerjee S, Silva-Alves CR, et al. A disintegrin and metalloprotease 17 in the cardiovascular and central nervous systems. Front Physiol 2016; 7: 469.
[http://dx.doi.org/10.3389/fphys.2016.00469] [PMID: 27803674]
[45]
Crackower MA, Sarao R, Oudit GY, et al. Angiotensin-converting enzyme 2 is an essential regulator of heart function. Nature 2002; 417(6891): 822-8.
[http://dx.doi.org/10.1038/nature00786] [PMID: 12075344]
[46]
Burrell LM, Burchill L, Dean RG, Griggs K, Patel SK, Velkoska E. Chronic kidney disease: cardiac and renal angiotensin-converting enzyme (ACE) 2 expression in rats after subtotal nephrectomy and the effect of ACE inhibition. Exp Physiol 2012; 97(4): 477-85.
[http://dx.doi.org/10.1113/expphysiol.2011.063156] [PMID: 22198016]
[47]
Lew RA, Warner FJ, Hanchapola I, et al. Angiotensin-converting enzyme 2 catalytic activity in human plasma is masked by an endogenous inhibitor. Exp Physiol 2008; 93(5): 685-93.
[http://dx.doi.org/10.1113/expphysiol.2007.040352] [PMID: 18223027]
[48]
Patel VB, Clarke N, Wang Z, et al. Angiotensin II induced proteolytic cleavage of myocardial ACE2 is mediated by TACE/ADAM-17: a positive feedback mechanism in the RAS. J Mol Cell Cardiol 2014; 66: 167-76.
[http://dx.doi.org/10.1016/j.yjmcc.2013.11.017] [PMID: 24332999]
[49]
Guzik TJ, Mohiddin SA, Dimarco A, et al. COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options. Cardiovasc Res 2020; 116(10): 1666-87.
[http://dx.doi.org/10.1093/cvr/cvaa106] [PMID: 32352535]
[50]
Palau V, Riera M, Soler MJ. ADAM17 inhibition may exert a protective effect on COVID-19. Nephrol Dial Transplant 2020; 35(6): 1071-2.
[http://dx.doi.org/10.1093/ndt/gfaa093] [PMID: 32291449]
[51]
Haga S, Nagata N, Okamura T, et al. TACE antagonists blocking ACE2 shedding caused by the spike protein of SARS-CoV are candidate antiviral compounds. Antiviral Res 2010; 85(3): 551-5.
[http://dx.doi.org/10.1016/j.antiviral.2009.12.001] [PMID: 19995578]
[52]
Matsuyama S, Nagata N, Shirato K, Kawase M, Takeda M, Taguchi F. Efficient activation of the severe acute respiratory syndrome coronavirus spike protein by the transmembrane protease TMPRSS2. J Virol 2010; 84(24): 12658-64.
[http://dx.doi.org/10.1128/JVI.01542-10] [PMID: 20926566]
[53]
Glowacka I, Bertram S, Müller MA, et al. Evidence that TMPRSS2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response. J Virol 2011; 85(9): 4122-34.
[http://dx.doi.org/10.1128/JVI.02232-10] [PMID: 21325420]
[54]
Shulla A, Heald-Sargent T, Subramanya G, Zhao J, Perlman S, Gallagher T. A transmembrane serine protease is linked to the severe acute respiratory syndrome coronavirus receptor and activates virus entry. J Virol 2011; 85(2): 873-82.
[http://dx.doi.org/10.1128/JVI.02062-10] [PMID: 21068237]
[55]
Hatesuer B, Bertram S, Mehnert N, et al. Tmprss2 is essential for influenza H1N1 virus pathogenesis in mice. PLoS Pathog 2013; 9(12): e1003774.
[http://dx.doi.org/10.1371/journal.ppat.1003774] [PMID: 24348248]
[56]
Bertram S, Dijkman R, Habjan M, et al. TMPRSS2 activates the human coronavirus 229E for cathepsin-independent host cell entry and is expressed in viral target cells in the respiratory epithelium. J Virol 2013; 87(11): 6150-60.
[http://dx.doi.org/10.1128/JVI.03372-12] [PMID: 23536651]
[57]
Lucas JM, True L, Hawley S, et al. The androgen-regulated type II serine protease TMPRSS2 is differentially expressed and mislocalized in prostate adenocarcinoma. J Pathol 2008; 215(2): 118-25.
[http://dx.doi.org/10.1002/path.2330] [PMID: 18338334]
[58]
Lucas JM, Heinlein C, Kim T, et al. The androgen-regulated protease TMPRSS2 activates a proteolytic cascade involving components of the tumor microenvironment and promotes prostate cancer metastasis. Cancer Discov 2014; 4(11): 1310-25.
[http://dx.doi.org/10.1158/2159-8290.CD-13-1010] [PMID: 25122198]
[59]
Ziegler CGK, Allon SJ, Nyquist SK, et al. HCA Lung Biological Network. Electronic address: lung-network@humancellatlas.org; HCA Lung Biological Network. SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues. Cell 2020; 181(5): 1016-1035.e19.
[http://dx.doi.org/10.1016/j.cell.2020.04.035] [PMID: 32413319]
[60]
Netzel-Arnett S, Hooper JD, Szabo R, et al. Membrane anchored serine proteases: a rapidly expanding group of cell surface proteolytic enzymes with potential roles in cancer. Cancer Metastasis Rev 2003; 22(2-3): 237-58.
[http://dx.doi.org/10.1023/A:1023003616848] [PMID: 12784999]
[61]
Szabo R, Bugge TH. Type II transmembrane serine proteases in development and disease. Int J Biochem Cell Biol 2008; 40(6-7): 1297-316.
[http://dx.doi.org/10.1016/j.biocel.2007.11.013] [PMID: 18191610]
[62]
Matsuyama S, Nao N, Shirato K, et al. Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells. Proc Natl Acad Sci USA 2020; 117(13): 7001-3.
[http://dx.doi.org/10.1073/pnas.2002589117] [PMID: 32165541]
[63]
Kim TS, Heinlein C, Hackman RC, Nelson PS. Phenotypic analysis of mice lacking the Tmprss2-encoded protease. Mol Cell Biol 2006; 26(3): 965-75.
[http://dx.doi.org/10.1128/MCB.26.3.965-975.2006] [PMID: 16428450]
[64]
Iwata-Yoshikawa N, Okamura T, Shimizu Y, Hasegawa H, Takeda M, Nagata N. TMPRSS2 contributes to virus spread and immunopathology in the airways of murine models after coronavirus infection. J Virol 2019; 93(6): e01815-8.
[http://dx.doi.org/10.1128/JVI.01815-18] [PMID: 30626688]
[65]
Cheng Z, Zhou J, To KK, et al. Identification of TMPRSS2 as a Susceptibility Gene for Severe 2009 Pandemic A(H1N1) Influenza and A(H7N9) Influenza. J Infect Dis 2015; 212(8): 1214-21.
[http://dx.doi.org/10.1093/infdis/jiv246] [PMID: 25904605]
[66]
Kawase M, Shirato K, van der Hoek L, Taguchi F, Matsuyama S. Simultaneous treatment of human bronchial epithelial cells with serine and cysteine protease inhibitors prevents severe acute respiratory syndrome coronavirus entry. J Virol 2012; 86(12): 6537-45.
[http://dx.doi.org/10.1128/JVI.00094-12] [PMID: 22496216]
[67]
Zhou Y, Vedantham P, Lu K, et al. Protease inhibitors targeting coronavirus and filovirus entry. Antiviral Res 2015; 116: 76-84.
[http://dx.doi.org/10.1016/j.antiviral.2015.01.011] [PMID: 25666761]
[68]
Lee MG, Kim KH, Park KY, Kim JS. Evaluation of anti-influenza effects of camostat in mice infected with non-adapted human influenza viruses. Arch Virol 1996; 141(10): 1979-89.
[http://dx.doi.org/10.1007/BF01718208] [PMID: 8920829]
[69]
Bahgat MM, Błazejewska P, Schughart K. Inhibition of lung serine proteases in mice: a potentially new approach to control influenza infection. Virol J 2011; 8: 27.
[http://dx.doi.org/10.1186/1743-422X-8-27] [PMID: 21251300]
[70]
Ramsey ML, Nuttall J, Hart PA. TACTIC Investigative Team. A phase 1/2 trial to evaluate the pharmacokinetics, safety, and efficacy of NI-03 in patients with chronic pancreatitis: study protocol for a randomized controlled trial on the assessment of camostat treatment in chronic pancreatitis (TACTIC). Trials 2019; 20(1): 501.
[http://dx.doi.org/10.1186/s13063-019-3606-y] [PMID: 31412955]
[71]
Yamamoto M, Matsuyama S, Li X, et al. Identification of nafamostat as a potent inhibitor of middle east respiratory syndrome coronavirus s protein-mediated membrane fusion using the split-protein-based cell-cell fusion assay. Antimicrob Agents Chemother 2016; 60(11): 6532-9.
[http://dx.doi.org/10.1128/AAC.01043-16] [PMID: 27550352]
[72]
Hoffmann M, Schroeder S, Kleine-Weber H, Müller MA, Drosten C, Pöhlmann S. Nafamostat mesylate blocks activation of SARS-CoV-2: New treatment option for COVID-19. Antimicrob Agents Chemother 2020; 64(6): e00754-20.
[http://dx.doi.org/10.1128/AAC.00754-20] [PMID: 32312781]
[73]
Tay MZ, Poh CM, Rénia L, MacAry PA, Ng LFP. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol 2020; 20(6): 363-74.
[http://dx.doi.org/10.1038/s41577-020-0311-8] [PMID: 32346093]
[74]
Shrimp JH, Kales SC, Sanderson PE, Simeonov A, Shen M, Hall MD. An enzymatic TMPRSS2 essay for essessment of clinical candidates and discovery of inhibitors as potential treatment of COVID-19. ACS Pharmacol Transl Sci 2020; 3(5): 997-1007.
[http://dx.doi.org/10.1021/acsptsci.0c00106] [PMID: 33062952]
[75]
Singh N, Decroly E, Khatib AM, Villoutreix BO. Structure-based drug repositioning over the human TMPRSS2 protease domain: search for chemical probes able to repress SARS-CoV-2 Spike protein cleavages. Eur J Pharm Sci 2020; 153: 105495.
[http://dx.doi.org/10.1016/j.ejps.2020.105495] [PMID: 32730844]
[76]
Chikhale RV, Gupta VK, Eldesoky GE, Wabaidur SM, Patil SA, Islam MA. Identification of potential anti-TMPRSS2 natural products through homology modelling, virtual screening and molecular dynamics simulation studies. J Biomol Struct Dyn 2020; 1-16.
[http://dx.doi.org/10.1080/07391102.2020.1798813] [PMID: 32741259]
[77]
Stopsack KH, Mucci LA, Antonarakis ES, Nelson PS, Kantoff PW. TMPRSS2 and COVID-19: Serendipity or opportunity for intervention? Cancer Discov 2020; 10(6): 779-82.
[http://dx.doi.org/10.1158/2159-8290.CD-20-0451] [PMID: 32276929]
[78]
Wang Q, Li W, Liu XS, et al. A hierarchical network of transcription factors governs androgen receptor-dependent prostate cancer growth. Mol Cell 2007; 27(3): 380-92.
[http://dx.doi.org/10.1016/j.molcel.2007.05.041] [PMID: 17679089]
[79]
Clinckemalie L, Spans L, Dubois V, et al. Androgen regulation of the TMPRSS2 gene and the effect of a SNP in an androgen response element. Mol Endocrinol 2013; 27(12): 2028-40.
[http://dx.doi.org/10.1210/me.2013-1098] [PMID: 24109594]
[80]
Mikkonen L, Pihlajamaa P, Sahu B, Zhang FP, Jänne OA. Androgen receptor and androgen-dependent gene expression in lung. Mol Cell Endocrinol 2010; 317(1-2): 14-24.
[http://dx.doi.org/10.1016/j.mce.2009.12.022] [PMID: 20035825]
[81]
Goren A, McCoy J, Wambier CG, et al. What does androgenetic alopecia have to do with COVID-19? An insight into a potential new therapy. Dermatol Ther (Heidelb) 2020; e13365: e13365.
[http://dx.doi.org/10.1111/dth.13365] [PMID: 32237190]
[82]
Pozzilli P, Lenzi A. Commentary: Testosterone, a key hormone in the context of COVID-19 pandemic. Metabolism 2020; 108: 154252.
[http://dx.doi.org/10.1016/j.metabol.2020.154252] [PMID: 32353355]
[83]
Montopoli M, Zumerle S, Vettor R, et al. Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (N = 4532). Ann Oncol 2020; 31(8): 1040-5.
[http://dx.doi.org/10.1016/j.annonc.2020.04.479] [PMID: 32387456]
[84]
Zhonghua L, Xing B, Xue Za Z. The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China. 2020; 41(2): 145-51.
[85]
Karlberg J, Chong DS, Lai WY. Do men have a higher case fatality rate of severe acute respiratory syndrome than women do? Am J Epidemiol 2004; 159(3): 229-31.
[http://dx.doi.org/10.1093/aje/kwh056] [PMID: 14742282]
[86]
Gupta N, Praharaj I, Bhatnagar T, et al. Severe acute respiratory illness surveillance for coronavirus disease. Indian J Med Res 2020; 151(2 & 3): 236-40.
[87]
Cai G. Tobacco-use disparity in gene expression of ACE2, the Receptor of 2019-nCov. Preprints 2020; 2020020051
[http://dx.doi.org/10.20944/preprints202002.0051.v1]
[88]
Arora VK, Schenkein E, Murali R, et al. Glucocorticoid receptor confers resistance to antiandrogens by bypassing androgen receptor blockade. Cell 2013; 155(6): 1309-22.
[http://dx.doi.org/10.1016/j.cell.2013.11.012] [PMID: 24315100]
[89]
Xu Z, Wang Y, Xiao ZG, et al. Nuclear receptor ERRα and transcription factor ERG form a reciprocal loop in the regulation of TMPRSS2:ERG fusion gene in prostate cancer. Oncogene 2018; 37(48): 6259-74.
[http://dx.doi.org/10.1038/s41388-018-0409-7] [PMID: 30042415]
[90]
Barnes BJ, Adrover JM, Baxter-Stoltzfus A, et al. Targeting potential drivers of COVID-19: Neutrophil extracellular traps. J Exp Med 2020; 217(6): e20200652.
[http://dx.doi.org/10.1084/jem.20200652] [PMID: 32302401]
[91]
McCoy J, Wambier CG, Vano-Galvan S, et al. Racial variations in COVID-19 deaths may be due to androgen receptor genetic variants associated with prostate cancer and androgenetic alopecia. Are anti-androgens a potential treatment for COVID-19? J Cosmet Dermatol 2020; 19(7): 1542-3.
[http://dx.doi.org/10.1111/jocd.13455] [PMID: 32333494]

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