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Review

SARS-CoV-2 protein drug targets landscape: a potential pharmacological insight view for the new drug development

, , , , &
Pages 225-237 | Received 29 Oct 2020, Accepted 07 Jan 2021, Published online: 27 Jan 2021

References

  • Chen J, Luo X, Qiu H, et al. Drug discovery and drug marketing with the critical roles of modern administration. Am J Transl Res. 2018;10(12):4302–4312.
  • Hughes JP, Rees S, Kalindjian SB, et al. Principles of early drug discovery. Br J Pharmacol. 2011;162(6):1239–1249.
  • Gashaw I, Ellinghaus P, Sommer A, et al. What makes a good drug target? Drug Discov Today. 2011;16(23–24):1037–1043.
  • Santos R, Ursu O, Gaulton A, et al. A comprehensive map of molecular drug targets. Nat Rev Drug Discov. 2017;16(1):19–34.
  • Lin Y, Mehta S, Küçük-mcginty H, et al. Drug target ontology to classify and integrate drug discovery data. J Biomed Semantics. 2017;8(1):50.
  • Schenone M, Dančík V, Wagner BK, et al. Target identification and mechanism of action in chemical biology and drug discovery. Nat Chem Biol. 2013;9(4):232–240.
  • Chakraborty C, Sharma A, Sharma G, et al. SARS-CoV-2 causing pneumonia-associated respiratory disorder (COVID-19): diagnostic and proposed therapeutic options. Eur Rev Med Pharmacol Sci. 2020;24(7):4016–4026.
  • Chakraborty C, Sharma AR, Bhattacharya M, et al. The 2019 novel coronavirus disease (COVID-19) pandemic: A zoonotic prospective. Asian Pac J Trop Med. 2020;13(6):242–246.
  • Gandhi RT, Lynch JB, Del rio C. Mild or moderate COVID-19. N Engl J Med. 2020;383(18):1757–1766.
  • Verity R, Okell LC, Dorigatti I, et al. Estimates of the severity of coronavirus disease 2019: a model-based analysis. Lancet Infect Dis. 2020;20(6):669–677.
  • Saha A, Sharma AR, Bhattacharya M, et al. Tocilizumab: A therapeutic option for the treatment of cytokine storm syndrome in COVID-19. Arch Med Res. 2020;51(6):595–597.
  • Chakraborty C, Sharma AR, Bhattacharya M, et al. COVID‐19: consider IL6 receptor antagonist for the therapy of cytokine storm syndrome in SARS‐CoV‐2 infected patients. J Med Virol. 2020;92(11):2260–2262.
  • Wu JT, Leung K, Bushman M, et al. Estimating clinical severity of COVID-19 from the transmission dynamics in Wuhan, China. Nat Med. 2020;26(4):506–510.
  • Yang S, Cao P, Du P, et al. Early estimation of the case fatality rate of COVID-19 in mainland China: a data-driven analysis. Ann Transl Med. 2020;8(4):128.
  • Saha A, Sharma AR, Bhattacharya M, et al. Probable molecular mechanism of remdesivir for the treatment of COVID-19: need to know more. Arch Med Res. 2020;51(6):585–586.
  • Saha RP, Singh MK, Samanta S, et al. Repurposing drugs, ongoing vaccine and new therapeutic development initiatives against COVID-19. Front Pharmacol. 2020;11:1258.
  • Hajduk PJ, Huth JR, Fesik SW. Druggability indices for protein targets derived from NMR-based screening data. J Med Chem. 2005;48(7):2518–2525.
  • Keller TH, Pichota A, Yin Z. A practical view of ‘druggability’. Curr Opin Chem Biol. 2006;10(4):357–361.
  • Imming P, Sinning C, Meyer A. Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006;5(10):821–834.
  • Zheng C, Han L, Yap C, et al. Therapeutic targets: progress of their exploration and investigation of their characteristics. Pharmacol Rev. 2006;58(2):259–279.
  • Russ AP, Lampel S. The druggable genome: an update. Drug Discov Today. 2005;10(23–24):1607–1610.
  • Mitsopoulos C, Schierz AC, Workman P, et al. Distinctive behaviors of druggable proteins in cellular networks. PLoS Comput Biol. 2015;11(12):e1004597.
  • Overington JP, Al-Lazikani B, Hopkins AL. How many drug targets are there? Nat Rev Drug Discov. 2006;5(12):993–996.
  • Bakheet TM, Doig AJ. Properties and identification of human protein drug targets. Bioinformatics. 2009;25(4):451–457.
  • Vinayagam A, Gibson TE, Lee H-J, et al. Controllability analysis of the directed human protein interaction network identifies disease genes and drug targets. Proc Natl Acad Sci U S A. 2016;113(18):4976–4981.
  • Chakraborty C. George Priya Doss C. Crucial protein based drug targets and potential inhibitors for osteoporosis: new hope and possibilities. Curr Drug Targets. 2013;14(14):1707–1713.
  • Mohamed SK, Nováček V, Nounu A. Discovering protein drug targets using knowledge graph embeddings. Bioinformatics. 2020;36(2):603–610.
  • Shyr ZA, Gorshkov K, Chen CZ, et al. Drug discovery strategies for SARS-CoV-2. J Pharmacol Exp Ther. 2020;375(1):127–138.
  • Senanayake SL. Drug repurposing strategies for COVID-19. Future Drug Discov. 2020;2(2). DOI:10.4155/fdd-2020-0010
  • Saxena A. Drug targets for COVID-19 therapeutics: ongoing global efforts. J Biosci. 2020;45(1):1–24.
  • Ghahremanpour MM, Tirado-Rives J, Deshmukh M, et al. Identification of 14 known drugs as inhibitors of the main protease of SARS-CoV-2. ACS Med Chem Lett. 2020;11(12):2526–2533.
  • Zhu W, Xu M, Chen CZ, et al. Identification of SARS-CoV-2 3CL protease inhibitors by a quantitative high-throughput screening. ACS Pharmacol Transl Sci. 2020;3(5):1008–1016.
  • Li G, De Clercq E. Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat Rev Drug Discov. 2020;19(3):149–150.
  • Bello M, Martínez-muñoz A, Balbuena-rebolledo I. Identification of saquinavir as a potent inhibitor of dimeric sars-cov2 main protease through mm/gbsa. J Mol Model. 2020;26(12):1.
  • Pattnaik GP, Chakraborty H. Entry inhibitors: efficient means to block viral infection. J Membr Biol. 2020;253(5):425–444.
  • Cannalire R, Stefanelli I, Cerchia C, et al. SARS-CoV-2 entry inhibitors: small molecules and peptides targeting virus or host cells. Int J Mol Sci. 2020;21(16):5707.
  • Xia S, Liu M, Wang C, et al. Inhibition of SARS-CoV-2 (previously 2019-ncov) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion. Cell Res. 2020;30(4):343–355.
  • Huang Y, Yang C, Xu X-F, et al. Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for covid-19.acta. Pharmacol Sin. 2020;41(9):1141–1149.
  • Huang J, Huang H, Wang D, et al. Immunological strategies against spike protein: neutralizing antibodies and vaccine development for COVID-19. Clin Transl Med. 2020;10(6):e184.
  • Dhama K, Sharun K, Tiwari R, et al. COVID-19, an emerging coronavirus infection: advances and prospects in designing and developing vaccines, immunotherapeutics, and therapeutics. Hum Vaccin Immunother. 2020;16(6):1232–1238.
  • Lau JL, Dunn MK. Therapeutic peptides: historical perspectives, current development trends, and future directions. Bioorg Med Chem. 2018;26(10):2700–2707.
  • Mahendran ASK, Lim YS, Fang C-M, et al. The potential of antiviral peptides as COVID-19 therapeutics. Front Pharmacol. 2020;11:1475.
  • VanPatten S, He M, Altiti A, et al. Evidence supporting the use of peptides and peptidomimetics as potential SARS-CoV-2 (COVID-19) therapeutics. Future Med Chem. 2020;12(18):1647–1656.
  • Shang J, Wan Y, Luo C, et al. Cell entry mechanisms of SARS-CoV-2. Proc Natl Acad Sci U S A. 2020;117(21):11727–11734.
  • Xiu S, Dick A, Ju H, et al. Inhibitors of SARS-CoV-2 entry: current and future opportunities. J Med Chem. 2020;63(21):12256–12274.
  • Saponaro F, Rutigliano G, Sestito S, et al. Ace2 in the era of SARS-CoV-2: controversies and novel perspectives. Front Mol Biosci. 2020;7:588618.
  • Kawase M, Shirato K, van der hoek L, et al. 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):6537–6545.
  • 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.
  • Tiwari V, Beer JC, Sankaranarayanan NV, et al. Discovering small-molecule therapeutics against SARS-CoV-2. Drug Discov Today. 2020;25(8):1535–1544.
  • Breining P, Frølund AL, Højen JF, et al. Camostat mesylate against sars‐cov‐2 and COVID‐19–rationale, dosing and safety. Basic Clin Pharmacol Toxicol. 2020. DOI:10.1111/bcpt.13533
  • Saha A, Sharma AR, Bhattacharya M, et al. Response to: status of remdesivir: not yet beyond question! arch med res. 2020; S0188-4409(20)31686-6.
  • Gil ayuso-gontán C, Ginex T, Maestro I, et al. COVID-19: drug targets and potential treatments. J Med Chem. 2020;63(21):12359–12386.
  • Jin Z, Du X, Xu Y, et al. Structure of mpro from SARS-CoV-2 and discovery of its inhibitors. Nature. 2020 Jun01;582(7811):289–293.
  • Ton A-T, Gentile F, Hsing M, et al. Rapid identification of potential inhibitors of SARS-CoV-2 main protease by deep docking of 1.3 billion compounds. Mol Inform. 2020;39(8):2000028.
  • Wang L, Bao -B-B, Song G-Q, et al. Discovery of unsymmetrical aromatic disulfides as novel inhibitors of sars-cov main protease: chemical synthesis, biological evaluation, molecular docking and 3d-qsar study. Eur J Med Chem. 2017;137:450–461.
  • Ratia K, Saikatendu KS, Santarsiero BD, et al. Severe acute respiratory syndrome coronavirus papain-like protease: structure of a viral deubiquitinating enzyme. Proc Natl Acad Sci U S A. 2006;103(15):5717–5722.
  • Klemm T, Ebert G, Calleja DJ, et al. Mechanism and inhibition of the papain‐like protease, plpro, of sars‐cov‐2. Embo J. 2020;39(18):e106275.
  • Thiel V, Ivanov KA, Putics A, et al. Mechanisms and enzymes involved in SARS coronavirus genome expression. J Gen Virol. 2003;84(9):2305–2315.
  • Naqvi AAT, Fatima K, Mohammad T, et al. Insights into SARS-CoV-2 genome, structure, evolution, pathogenesis and therapies: structural genomics approach. Biochim Biophys Acta Mol Basis Dis. 2020;1866(10):165878.
  • Joshi RS, Jagdale SS, Bansode SB, et al. Discovery of potential multi-target-directed ligands by targeting host-specific SARS-CoV-2 structurally conserved main protease. J Biomol Struct Dyn. 2020;1–16. DOI:10.1080/07391102.2020.1760137.
  • Zhang L, Lin D, Sun X, et al. Crystal structure of sars-cov-2 main protease provides a basis for design of improved α-ketoamide inhibitors. Science. 2020;368(6489):409–412.
  • Jin Z, Du X, Xu Y, et al. Structure of m pro from SARS-CoV-2 and discovery of its inhibitors. Nature. 2020;582(7811):289–293.
  • Wu C, Liu Y, Yang Y, et al. Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharm Sin B. 2020;10(5):766–788.
  • Yang H, Yang M, Ding Y, et al. The crystal structures of severe acute respiratory syndrome virus main protease and its complex with an inhibitor. Proc Natl Acad Sci U S A. 2003;100(23):13190–13195.
  • Ul qamar MT, Alqahtani SM, Alamri MA, et al. Structural basis of SARS-CoV-2 3CLpro and anti-COVID-19 drug discovery from medicinal plants. J Pharm Anal. 2020;10(4):313–319.
  • Anand K, Ziebuhr J, Wadhwani P, et al. Coronavirus main proteinase (3CLpro) structure: basis for design of anti-SARS drugs. Science. 2003;300(5626):1763–1767.
  • Anand K, Palm GJ, Mesters JR, et al. Structure of coronavirus main proteinase reveals combination of a chymotrypsin fold with an extra α‐helical domain. Embo J. 2002;21(13):3213–3224.
  • Dai W, Zhang B, Jiang X-M, et al. Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease. Science. 2020;368(6497):1331–1335.
  • Vuong W, Khan MB, Fischer C, et al. Feline coronavirus drug inhibits the main protease of SARS-CoV-2 and blocks virus replication. Nat Commun. 2020;11(1):4282.
  • Ma C, Sacco MD, Hurst B, et al. Boceprevir, gc-376, and calpain inhibitors ii, xii inhibit SARS-CoV-2 viral replication by targeting the viral main protease. Cell Res. 2020;(8):678–692.
  • Ma C, Hu Y, Townsend JA, et al. Ebselen, disulfiram, carmofur, px-12, tideglusib, and shikonin are nonspecific promiscuous SARS-CoV-2 main protease inhibitors. ACS Pharmacol Transl Sci. 2020;3(6):1265–1277.
  • Bello M, Martínez-muñoz A, Balbuena-rebolledo I. Identification of saquinavir as a potent inhibitor of dimeric sars-cov2 main protease through mm/gbsa. J Mol Model. 2020;26(12):340.
  • Martiniano B. Prediction of potential inhibitors of the dimeric sars-cov2 main proteinase through the mm/gbsa approach. J Mol Graph Model. 2020. DOI:10.1016/j.jmgm.2020.107762
  • Harcourt BH, Jukneliene D, Kanjanahaluethai A, et al. Identification of severe acute respiratory syndrome coronavirus replicase products and characterization of papain-like protease activity. J Virol. 2004;78(24):13600–13612.
  • Gao X, Qin B, Chen P, et al. Crystal structure of SARS-CoV-2 papain-like protease. Acta Pharm Sin B. 2020. DOI:10.1016/j.apsb.2020.08.014.
  • Krishna SS, Majumdar I, Grishin NV. Survey and summary: structural classification of zinc fingers. Nucleic Acids Res. 2003;31(2):532–550.
  • Gao X, Qin B, Chen P, et al. Crystal structure of SARS-CoV-2 papain-like protease. Acta Pharm Sin B. 2020. DOI:10.1016/j.apsb.2020.08.014
  • Machitani M, Yasukawa M, Nakashima J, et al. RNA-dependent RNA polymerase, rdrp, a promising therapeutic target for cancer and potentially covid‐19. Cancer Sci. 2020;111(11):3976–3984.
  • McDonald SM. RNA synthetic mechanisms employed by diverse families of rna viruses. Wiley Interdiscip Rev RNA. 2013;4(4):351–367.
  • Gao Y, Yan L, Huang Y, et al. Structure of the RNA-dependent RNA polymerase from COVID-19 virus. Science. 2020;368(6492):779–782.
  • Moustafa IM, Shen H, Morton B, et al. Molecular dynamics simulations of viral RNA polymerases link conserved and correlated motions of functional elements to fidelity. J Mol Biol. 2020;410(1):159–181.
  • Yin W, Mao C, Luan X, et al. Structural basis for inhibition of the rna-dependent rna polymerase from SARS-CoV-2 by remdesivir. Science. 2020;368(6498):1499–1504.
  • Nejadi babadaei MM, Hasan A, Vahdani Y, et al. Development of remdesivir repositioning as a nucleotide analog against COVID-19 RNA dependent RNA polymerase. J Biomol Struct Dyn. 2020. DOI:10.1080/07391102.2020.1767210
  • Wang Y, Anirudhan V, Du R, et al. RNA-dependent RNA polymerase of sars‐cov‐2 as a therapeutic target. J Med Virol. 2020. DOI:10.1002/jmv.26264
  • Zhu W, CZ C, Gorshkov K, et al. RNA-dependent RNA polymerase as a target for COVID-19 drug discovery. SLAS Discov. 2020;25(10):1141–1151.
  • Elfiky AA. SARS-CoV-2 RNA-dependent RNA polymerase (rdrp) targeting: an in silico perspective. J Biomol Struct Dyn. 2020;1–9. DOI:10.1080/07391102.2020.1761882
  • Wakchaure PD, Ghosh S, Ganguly B. Revealing the inhibition mechanism of RNA-dependent RNA polymerase (rdrp) of SARS-CoV-2 by remdesivir and nucleotide analogues: a molecular dynamics simulation study. J Phys Chem B. 2020;124(47):10641–10652.
  • Gordon CJ, Tchesnokov EP, Woolner E, et al. Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency. J Biol Chem. 2020;295(20):6785–6797.
  • Snijder E, Decroly E, Ziebuhr J. The nonstructural proteins directing coronavirus RNA synthesis and processing. Adv Virus Res. 2016;96:59–126.
  • Romano M, Ruggiero A, Squeglia F, et al. A structural view of SARS-CoV-2 rna replication machinery: rna synthesis, proofreading and final capping. Cells. 2020;9(5):1267.
  • Jia Z, Yan L, Ren Z, et al. Delicate structural coordination of the severe acute respiratory syndrome coronavirus nsp13 upon atp hydrolysis. Nucleic Acids Res. 2019;47(12):6538–6550.
  • Chen J, Malone B, Llewellyn E, et al. Structural basis for helicase-polymerase coupling in the SARS-CoV-2 replication-transcription complex. Cell. 2020;182(6):1560–1573.e13.
  • Ivanov KA, Ziebuhr J. Human coronavirus 229E nonstructural protein 13: characterization of duplex-unwinding, nucleoside triphosphatase, and RNA 5′-triphosphatase activities. J Virol. 2004;78(14):7833–7838.
  • Habtemariam S, Nabavi SF, Banach M, et al. Should we try SARS-CoV-2 helicase inhibitors for COVID-19 therapy? Arch Med Res. 2020;51(7):733–735.
  • Lan J, Ge J, Yu J, et al. Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature. 2020;581(7807):215–220.
  • Shang J, Wan Y, Liu C, et al. Structure of mouse coronavirus spike protein complexed with receptor reveals mechanism for viral entry. PLoS Pathog. 2020;16(3):e1008392.
  • Saputri DS, Li S, Van eerden FJ, et al. Flexible, functional, and familiar: characteristics of SARS-CoV-2 spike protein evolution. Front Microbiol. 2020;11:2112.
  • Bhattacharya M, Sharma AR, Mallick B, et al. Immunoinformatics approach to understand molecular interaction between multi-epitopic regions of SARS-CoV-2 spike-protein with TLR4/MD-2 complex. Infect Genet Evol. 2020;85:104587.
  • Walls AC, Park Y-J, Tortorici MA, et al. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell. 2020;;181(2):281–292.e6.
  • Jiang S, Du L, Shi Z. An emerging coronavirus causing pneumonia outbreak in wuhan, china: calling for developing therapeutic and prophylactic strategies. Emerg Microbes Infect. 2020;9(1):275–277.
  • Singh B. Role of key point mutations in receptor binding domain of SARS-CoV-2 spike glycoprotein. Infect Disord Drug Targets. 2020;20. DOI:10.2174/1871526520666200804161650.
  • Yan R, Zhang Y, Li Y, et al. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science. 2020;367(6485):1444–1448.
  • Yang J, Petitjean S, Derclaye S, et al. Molecular interaction and inhibition of SARS-CoV-2 binding to the ACE2 receptor. Nat Commun. 2020;11(1):4541.
  • Mittal A, Manjunath K, Ranjan RK, et al. COVID-19 pandemic: insights into structure, function, and hACE2 receptor recognition by SARS-CoV-2. PLoS Pathog. 2020;16(8):e1008762.
  • Jaimes J, Millet J, Whittaker G. Proteolytic cleavage of the SARS-CoV-2 spike protein and the role of the novel S1/S2 site. iScience. 2020;23(6):101212.
  • Zhou Y, Vedantham P, Lu K, et al. Protease inhibitors targeting coronavirus and filovirus entry. Antiviral Res. 2015;116:76–84.
  • Ehmke V, Winkler E, Banner DW, et al. Optimization of triazine nitriles as rhodesain inhibitors: structure–activity relationships, bioisosteric imidazopyridine nitriles, and X‐ray crystal structure analysis with human cathepsin L. Chem Med Chem. 2013;8(6):967–975.
  • Fujishima A, Imai Y, Nomura T, et al. The crystal structure of human cathepsin L complexed with E-64. FEBS Lett. 1997;407(1):47–50.
  • Yuan L, Zou C, Ge W, et al. A novel cathepsin L inhibitor prevents the progression of idiopathic pulmonary fibrosis. Bioorg Chem. 2020;94:103417.
  • Sacco MD, Ma C, Lagarias P, et al. Structure and inhibition of the SARS-CoV-2 main protease reveal strategy for developing dual inhibitors against m pro and cathepsin l. Sci Adv. 2020;6(50):eabe0751.
  • Hu Y, Ma C, Szeto T, et al. Boceprevir, calpain inhibitors II and XII, and GC-376 have broad-spectrum antiviral activity against coronaviruses in cell culture. bioRxiv. 2020. DOI:10.1101/2020.10.30.362335
  • Coutard B, Valle C, de lamballerie X, et al. The spike glycoprotein of the new coronavirus 2019-ncov contains a furin-like cleavage site absent in cov of the same clade. Antiviral Res. 2020;176:104742.
  • Millet JK, Whittaker GR. Host cell proteases: critical determinants of coronavirus tropism and pathogenesis. Virus Res. 2015;202:120–134.
  • Henrich S, Cameron A, bourenkov GP, et al. Than ME The crystal structure of the proprotein processing proteinase furin explains its stringent specificity. Natur Struct Biol. 2003;10(7):520–526.
  • Dahms SO, Arciniega M, Steinmetzer T, et al. Structure of the unliganded form of the proprotein convertase furin suggests activation by a substrate-induced mechanism. Proc Natl Acad Sci U S A. .2016;113(40):11196–11201.
  • 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):4122–4134.
  • Lukassen S, Chua RL, Trefzer T, et al. SARS‐CoV‐2 receptor ACE 2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells. Embo J. 2020;39(10):e105114.
  • Sakai K, Ami Y, Tahara M, et al. The host protease TMPRSS2 plays a major role in in vivo replication of emerging H7N9 and seasonal influenza viruses. J Virol. 2014;88(10):5608–5616.
  • Durdaği S. Virtual drug repurposing study against SARS-CoV-2 TMPRSS2 target. Turk J Biol. 2020;44(3):185–191.
  • Huggins DJ. Structural analysis of experimental drugs binding to the SARS-CoV-2 target TMPRSS2. J Mol Graph Model. 2020;100:107710.
  • Hoffmann M, Kleine-weber H, Schroeder S, et al. Müller ma. 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.
  • Ni W, Yang X, Yang D, et al. Role of angiotensin-converting enzyme 2 (ACE2) in COVID-19. Crit Care. 2020;24(1):1–10.
  • Kuba K, Imai Y, Ohto-nakanishi T, et al. Trilogy of ACE2: A peptidase in the renin–angiotensin system, a SARS receptor, and a partner for amino acid transporters. Pharmacol Ther. 2010;128(1):119–128.
  • Xu H, Zhong L, Deng J, et al. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci. 2020;12(1):1–5.
  • Ren X, Glende J, Al-falah M, et al. Analysis of ACE2 in polarized epithelial cells: surface expression and function as receptor for severe acute respiratory syndrome-associated coronavirus.J. Gen Virol. 2006;87(6):1691–1695.
  • Towler P, Staker B, Prasad SG, et al. ACE2 X-ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysis. J Biol Chem. 2004;279(17):17996–18007.
  • Devaux CA, Rolain J-M, Raoult D. ACE2 receptor polymorphism: susceptibility to SARS-CoV-2, hypertension, multi-organ failure, and covid-19 disease outcome. J Microbiol Immunol Infect. 2020;53(3):425–435.
  • 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):taaa041.
  • Elfiky AA, Ribavirin R, Sofosbuvir G. Tenofovir against SARS-CoV-2 RNA-dependent RNA polymerase (rdrp): a molecular docking study. Life Sci. 2020;253:117592.
  • Du YX, Chen XP. Favipiravir: pharmacokinetics and concerns about clinical trials for 2019‐nCoV infection. Clin Pharmacol Ther 2020;108(2):242–247.
  • Tanner JA, Zheng B-J, Zhou J, et al. The adamantane-derived bananins are potent inhibitors of the helicase activities and replication of SARS coronavirus. Chem Biol. 2005;12(3):303–311.
  • Adedeji AO, Singh K, Calcaterra NE, et al. Severe acute respiratory syndrome coronavirus replication inhibitor that interferes with the nucleic acid unwinding of the viral helicase. Antimicrob Agents Chemother. 2012;56(9):4718–4728.
  • Adedeji AO, Severson W, Jonsson C, et al. Novel inhibitors of severe acute respiratory syndrome coronavirus entry that act by three distinct mechanisms. J Virol. 2013;87(14):8017–8028.
  • Barton C, Kouokam JC, Lasnik AB, et al. Activity of and effect of subcutaneous treatment with the broad-spectrum antiviral lectin griffithsin in two laboratory rodent models. Antimicrob Agents Chemother. 2014;58(1):120–127.
  • Dahms SO, Hardes K, Steinmetzer T, et al. X-ray structures of the proprotein convertase furin bound with substrate analogue inhibitors reveal substrate specificity determinants beyond the s4 pocket. Biochemistry. 2018;57(6):925–934.
  • Shen LW, Mao HJ, Wu YL, et al. TMPRSS2: A potential target for treatment of influenza virus and coronavirus infections. Biochimie. 2017;142:1–10.
  • Wang X, Dhindsa R, Povysil G, et al. Transcriptional inhibition of host viral entry proteins as a therapeutic strategy for SARS-CoV-2. Drug Dev Res. 2020. DOI:10.20944/preprints202003.0360.v1
  • Rothlin RP, Vetulli HM, Duarte M, et al. Telmisartan as tentative angiotensin receptor blocker therapeutic for COVID-19. Drug Dev Res. 2020;81(7):768–770.

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