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Current Medicinal Chemistry

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Review Article

Structural Basis for the Understanding of Entry Inhibitors against SARS Viruses

Author(s): Prem Kumar Kushwaha, Neha Kumari, Sneha Nayak, Keshav Kishor and Ashoke Sharon*

Volume 29, Issue 4, 2022

Published on: 14 May, 2021

Page: [666 - 681] Pages: 16

DOI: 10.2174/0929867328666210514122418

Price: $65

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Abstract

Outbreaks due to Severe Acute Respiratory Syndrome-Corona virus 2 (SARSCoV- 2) initiated in Wuhan city, China, in December 2019 and continued to spread Internationally, posing a pandemic threat as declared by WHO and as of March 10, 2021, confirmed cases reached 118 million along with 2.6 million deaths worldwide. In the absence of specific antiviral medication, symptomatic treatment and physical isolation remain the options to control the disease and contagion. The recent clinical trials on antiviral drugs highlighted some promising compounds such as umifenovir (haemagglutininand has only 70% similarity to SAmediated fusion inhibitor), remdesivir (RdRp nucleoside inhibitor), and favipiravir (RdRp Inhibitor). WHO launched a multinational clinical trial on several promising analogs as a potential treatment to combat SARS infection. This situation urges a holistic approach to invent safe and specific drugs as a prophylactic and therapeutic cure for SARS-related viral diseases, including COVID-19.

It is significant to note that researchers worldwide have been doing their best to handle the crisis and have produced an extensive and promising literature body. It opens a scope and allows understanding the viral entry at the molecular level. A structure-based approach can reveal the molecular-level understanding of viral entry interaction. The ligand profiling and non-covalent interactions among participating amino-acid residues are critical information to delineate a structural interpretation. The structural investigation of SARS virus entry into host cells will reveal the possible strategy for designing drugs like entry inhibitors.

The structure-based approach demonstrates details at the 3D molecular level. It shows specificity about SARS-CoV-2 spike interaction, which uses human angiotensin-converting enzyme 2 (ACE2) as a receptor for entry, and the human protease completes the process of viral fusion and infection.

The 3D structural studies reveal the existence of two units, namely S1 and S2. S1 is called a receptor-binding domain (RBD) and responsible for interacting with the host (ACE2), and the S2 unit participates in the fusion of viral and cellular membranes. TMPRSS2 mediates the cleavage at the S1/S2 subunit interface in the S-protein of SARS CoV-2, leading to viral fusion. Conformational difference associated with S1 binding alters ACE2 interaction and inhibits viral fusion. Overall, the detailed 3D structural studies help understand the 3D structural basis of interaction between viruses with host factors and open scope for the new drug discovery process targeting SARS-related virus entry into the host cell.

Keywords: Severe acute respiratory syndrome (SARS), SARS-CoV2, COVID-19, receptor-binding domain(RBD), protein-protein interface, entry inhibitors.

« Previous Next »
[1]
Cui, J.; Li, F.; Shi, Z-L. Origin and evolution of pathogenic coronaviruses. Nat. Rev. Microbiol., 2019, 17(3), 181-192.
[http://dx.doi.org/10.1038/s41579-018-0118-9] [PMID: 30531947]
[2]
de Wit, E.; van Doremalen, N.; Falzarano, D.; Munster, V.J. SARS and MERS: recent insights into emerging coronaviruses. Nat. Rev. Microbiol., 2016, 14(8), 523-534.
[http://dx.doi.org/10.1038/nrmicro.2016.81] [PMID: 27344959]
[3]
Zhong, N.S.; Zheng, B.J.; Li, Y.M.; Poon, ; Xie, Z.H.; Chan, K.H.; Li, P.H.; Tan, S.Y.; Chang, Q.; Xie, J.P.; Liu, X.Q.; Xu, J.; Li, D.X.; Yuen, K.Y.; Peiris, ; Guan, Y. Epidemiology and cause of severe acute respiratory syndrome (SARS) in Guangdong, People’s Republic of China, in February, 2003. Lancet, 2003, 362(9393), 1353-1358.
[http://dx.doi.org/10.1016/S0140-6736(03)14630-2] [PMID: 14585636]
[4]
Guan, Y.; Zheng, B.J.; He, Y.Q.; Liu, X.L.; Zhuang, Z.X.; Cheung, C.L.; Luo, S.W.; Li, P.H.; Zhang, L.J.; Guan, Y.J.; Butt, K.M.; Wong, K.L.; Chan, K.W.; Lim, W.; Shortridge, K.F.; Yuen, K.Y.; Peiris, J.S.; Poon, L.L. Isolation and characterization of viruses related to the SARS coronavirus from animals in southern China. Science, 2003, 302(5643), 276-278.
[http://dx.doi.org/10.1126/science.1087139] [PMID: 12958366]
[5]
Li, W.; Shi, Z.; Yu, M.; Ren, W.; Smith, C.; Epstein, J.H.; Wang, H.; Crameri, G.; Hu, Z.; Zhang, H.; Zhang, J.; McEachern, J.; Field, H.; Daszak, P.; Eaton, B.T.; Zhang, S.; Wang, L.F. Bats are natural reservoirs of SARS-like coronaviruses. Science, 2005, 310(5748), 676-679.
[http://dx.doi.org/10.1126/science.1118391] [PMID: 16195424]
[6]
Zhu, Z.; Lian, X.; Su, X.; Wu, W.; Marraro, G.A.; Zeng, Y. From SARS and MERS to COVID-19: a brief summary and comparison of severe acute respiratory infections caused by three highly pathogenic human coronaviruses. Respir. Res., 2020, 21(1), 224.
[http://dx.doi.org/10.1186/s12931-020-01479-w] [PMID: 32854739]
[7]
Sahin, A.R.; Erdogan, A.; Agaoglu, P.M.; Dineri, Y.; Cakirci, A.Y.; Senel, M.E.; Okyay, R.A.; Tasdogan, A.M. 2019 Novel Coronavirus (COVID-19) Outbreak: A Review of the Current Literature. Eurasian Journal of Medicine and Oncology, 2020.
[8]
Zhao, S.; Lin, Q.; Ran, J.; Musa, S.S.; Yang, G.; Wang, W.; Lou, Y.; Gao, D.; Yang, L.; He, D.; Wang, M.H. Preliminary estimation of the basic reproduction number of novel coronavirus (2019-nCoV) in China, from 2019 to 2020: A data-driven analysis in the early phase of the outbreak. Int. J. Infect. Dis., 2020, 92, 214-217.
[http://dx.doi.org/10.1016/j.ijid.2020.01.050] [PMID: 32007643]
[9]
Salata, C.; Calistri, A.; Parolin, C.; Palù, G. Coronaviruses: a paradigm of new emerging zoonotic diseases. Pathog. Dis., 2019, 77(9), ftaa006.
[http://dx.doi.org/10.1093/femspd/ftaa006] [PMID: 32065221]
[10]
Mahase, E. Covid-19: WHO declares pandemic because of “alarming levels” of spread, severity, and inaction. BMJ, 2020, 368, m1036.
[http://dx.doi.org/10.1136/bmj.m1036] [PMID: 32165426]
[11]
McIntosh, K.; Dees, J.H.; Becker, W.B.; Kapikian, A.Z.; Chanock, R.M. Recovery in tracheal organ cultures of novel viruses from patients with respiratory disease. Proc. Natl. Acad. Sci. USA, 1967, 57(4), 933-940.
[http://dx.doi.org/10.1073/pnas.57.4.933] [PMID: 5231356]
[12]
Pillaiyar, T.; Meenakshisundaram, S.; Manickam, M. Recent discovery and development of inhibitors targeting coronaviruses. Drug Discov. Today, 2020, 25(4), 668-688.
[http://dx.doi.org/10.1016/j.drudis.2020.01.015] [PMID: 32006468]
[13]
Satarker, S.; Nampoothiri, M. Structural Proteins in Severe Acute Respiratory Syndrome Coronavirus-2. Arch. Med. Res., 2020, 51(6), 482-491.
[http://dx.doi.org/10.1016/j.arcmed.2020.05.012] [PMID: 32493627]
[14]
Delmas, B.; Laude, H. Assembly of coronavirus spike protein into trimers and its role in epitope expression. J. Virol., 1990, 64(11), 5367-5375.
[http://dx.doi.org/10.1128/jvi.64.11.5367-5375.1990] [PMID: 2170676]
[15]
Abraham, S.; Kienzle, T.E.; Lapps, W.; Brian, D.A. Deduced sequence of the bovine coronavirus spike protein and identification of the internal proteolytic cleavage site. Virology, 1990, 176(1), 296-301.
[http://dx.doi.org/10.1016/0042-6822(90)90257-R] [PMID: 2184576]
[16]
Shirato, K.; Kawase, M.; Matsuyama, S. Middle East respiratory syndrome coronavirus infection mediated by the transmembrane serine protease TMPRSS2. J. Virol., 2013, 87(23), 12552-12561.
[http://dx.doi.org/10.1128/JVI.01890-13] [PMID: 24027332]
[17]
Xiu, S.; Dick, A.; Ju, H.; Mirzaie, S.; Abdi, F.; Cocklin, S.; Zhan, P.; Liu, X. Inhibitors of SARS-CoV-2 Entry: Current and Future Opportunities. J. Med. Chem., 2020, 63(21), 12256-12274.
[http://dx.doi.org/10.1021/acs.jmedchem.0c00502] [PMID: 32539378]
[18]
Wu, C.; Zheng, M.; Yang, Y.; Gu, X.; Yang, K.; Li, M.; Liu, Y.; Zhang, Q.; Zhang, P.; Wang, Y.; Wang, Q.; Xu, Y.; Zhou, Y.; Zhang, Y.; Chen, L.; Li, H. Furin: A Potential Therapeutic Target for COVID-19. iScience, 2020, 23(10), 101642.
[http://dx.doi.org/10.1016/j.isci.2020.101642] [PMID: 33043282]
[19]
Papa, G.; Mallery, D.L.; Albecka, A.; Welch, L.G.; Cattin-Ortolá, J.; Luptak, J.; Paul, D.; McMahon, H.T.; Goodfellow, I.G.; Carter, A.; Munro, S.; James, L.C. Furin cleavage of SARS-CoV-2 Spike promotes but is not essential for infection and cell-cell fusion. PLoS Pathog., 2021, 17(1), e1009246.
[http://dx.doi.org/10.1371/journal.ppat.1009246] [PMID: 33493182]
[20]
Gralinski, L.E.; Menachery, V.D. Return of the Coronavirus: 2019-nCoV. Viruses, 2020, 12(2), 135.
[http://dx.doi.org/10.3390/v12020135] [PMID: 31991541]
[21]
World Health Organization. Modes of transmission of virus causing COVID-19: implications for IPC precaution recommendations. Available at: https://www.who.int/news-room/commentaries/detail/modes-of-transmission-of-virus-causing-covid-19-implications-for-ipc-precaution-recommendations
[22]
Signorelli, C.; Odone, A.; Riccò, M.; Bellini, L.; Croci, R.; Oradini-Alacreu, A.; Fiacchini, D.; Burioni, R. Major sports events and the transmission of SARS-CoV-2: analysis of seven case-studies in Europe. Acta Biomed., 2020, 91(2), 242-244.
[PMID: 32420959]
[23]
Ong, S.W.X.; Tan, Y.K.; Chia, P.Y.; Lee, T.H.; Ng, O.T.; Wong, M.S.Y.; Marimuthu, K. Air, surface environmental, and personal protective equipment contamination by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) from a symptomatic patient. JAMA, 2020, 323(16), 1610-1612.
[http://dx.doi.org/10.1001/jama.2020.3227] [PMID: 32129805]
[24]
van Doremalen, N.; Bushmaker, T.; Morris, D.H.; Holbrook, M.G.; Gamble, A.; Williamson, B.N.; Tamin, A.; Harcourt, J.L.; Thornburg, N.J.; Gerber, S.I.; Lloyd-Smith, J.O.; de Wit, E.; Munster, V.J. Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1. N. Engl. J. Med., 2020, 382(16), 1564-1567.
[http://dx.doi.org/10.1056/NEJMc2004973] [PMID: 32182409]
[25]
Wang, K. SARS-CoV-2 invades host cells via a novel route: CD147-spike protein BioRxiv, 2020.
[http://dx.doi.org/10.1101/2020.03.14.988345]
[26]
Kumar, S.; Nyodu, R.; Maurya, V.K.; Saxena, S.K. Morphology, Genome Organization, Replication, and Pathogenesis of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). In: Coronavirus Disease 2019 (COVID-19); Saxena, S.K., Ed.; Springer, 2020; pp. 23-31.
[27]
Ortega, J.T.; Serrano, M.L.; Pujol, F.H.; Rangel, H.R. Role of changes in SARS-CoV-2 spike protein in the interaction with the human ACE2 receptor: An in silico analysis. EXCLI J., 2020, 19, 410-417.
[PMID: 32210742]
[28]
Yan, R.; Zhang, Y.; Li, Y.; Xia, L.; Guo, Y.; Zhou, Q. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science, 2020, 367(6485), 1444-1448.
[http://dx.doi.org/10.1126/science.abb2762] [PMID: 32132184]
[29]
Shang, J.; Ye, G.; Shi, K.; Wan, Y.; Luo, C.; Aihara, H.; Geng, Q.; Auerbach, A.; Li, F. Structural basis of receptor recognition by SARS-CoV-2. Nature, 2020, 581(7807), 221-224.
[http://dx.doi.org/10.1038/s41586-020-2179-y] [PMID: 32225175]
[30]
Song, W.; Gui, M.; Wang, X.; Xiang, Y.; Luo, C.; Aihara, H.; Geng, Q.; Auerbach, A.; Li, F. Cryo-EM structure of the SARS coronavirus spike glycoprotein in complex with its host cell receptor ACE2. PLoS Pathog., 2018, 14(8), e1007236.
[http://dx.doi.org/10.1371/journal.ppat.1007236] [PMID: 30102747]
[31]
Vincent, M.J.; Bergeron, E.; Benjannet, S.; Erickson, B.R.; Rollin, P.E.; Ksiazek, T.G.; Seidah, N.G.; Nichol, S.T. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol. J., 2005, 2(1), 69.
[http://dx.doi.org/10.1186/1743-422X-2-69] [PMID: 16115318]
[32]
Hu, H.; Li, L.; Kao, R.Y.; Kou, B.; Wang, Z.; Zhang, L.; Zhang, H.; Hao, Z.; Tsui, W.H.; Ni, A.; Cui, L.; Fan, B.; Guo, F.; Rao, S.; Jiang, C.; Li, Q.; Sun, M.; He, W.; Liu, G. Screening and identification of linear B-cell epitopes and entry-blocking peptide of severe acute respiratory syndrome (SARS)-associated coronavirus using synthetic overlapping peptide library. J. Comb. Chem., 2005, 7(5), 648-656.
[http://dx.doi.org/10.1021/cc0500607] [PMID: 16153058]
[33]
Struck, A.W.; Axmann, M.; Pfefferle, S.; Drosten, C.; Meyer, B. A hexapeptide of the receptor-binding domain of SARS corona virus spike protein blocks viral entry into host cells via the human receptor ACE2. Antiviral Res., 2012, 94(3), 288-296.
[http://dx.doi.org/10.1016/j.antiviral.2011.12.012] [PMID: 22265858]
[34]
Robertson, N.S.; Spring, D.R. Using peptidomimetics and constrained peptides as valuable tools for inhibiting protein–protein interactions. Molecules, 2018, 23(4), 959.
[http://dx.doi.org/10.3390/molecules23040959] [PMID: 29671834]
[35]
Donoghue, M.; Hsieh, F.; Baronas, E.; Godbout, K.; Gosselin, M.; Stagliano, N.; Donovan, M.; Woolf, B.; Robison, K.; Jeyaseelan, R.; Breitbart, R.E.; Acton, S. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ. Res., 2000, 87(5), E1-E9.
[http://dx.doi.org/10.1161/01.RES.87.5.e1] [PMID: 10969042]
[36]
Zhang, H.; Penninger, J.M.; Li, Y.; Zhong, N.; Slutsky, A.S. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med., 2020, 46(4), 586-590.
[http://dx.doi.org/10.1007/s00134-020-05985-9] [PMID: 32125455]
[37]
Lipinski, C.A.; Lombardo, F.; Dominy, B.W.; Feeney, P.J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev., 2001, 46(1-3), 3-26.
[http://dx.doi.org/10.1016/S0169-409X(00)00129-0] [PMID: 11259830]
[38]
Adedeji, A.O.; Severson, W.; Jonsson, C.; Singh, K.; Weiss, S.R.; Sarafianos, S.G. Novel inhibitors of severe acute respiratory syndrome coronavirus entry that act by three distinct mechanisms. J. Virol., 2013, 87(14), 8017-8028.
[http://dx.doi.org/10.1128/JVI.00998-13] [PMID: 23678171]
[39]
Huentelman, M.J.; Zubcevic, J.; Hernández Prada, J.A.; Xiao, X.; Dimitrov, D.S.; Raizada, M.K.; Ostrov, D.A. Structure-based discovery of a novel angiotensin-converting enzyme 2 inhibitor. Hypertension, 2004, 44(6), 903-906.
[http://dx.doi.org/10.1161/01.HYP.0000146120.29648.36] [PMID: 15492138]
[40]
Uzunova, K.; Filipova, E.; Pavlova, V.; Vekov, T. Insights into antiviral mechanisms of remdesivir, lopinavir/ritonavir and chloroquine/hydroxychloroquine affecting the new SARS-CoV-2. Biomed. Pharmacother., 2020, 131, 110668.
[http://dx.doi.org/10.1016/j.biopha.2020.110668] [PMID: 32861965]
[41]
Wang, M.; Cao, R.; Zhang, L.; Yang, X.; Liu, J.; Xu, M.; Shi, Z.; Hu, Z.; Zhong, W.; Xiao, G. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res., 2020, 30(3), 269-271.
[http://dx.doi.org/10.1038/s41422-020-0282-0] [PMID: 32020029]
[42]
Rainsford, K.D.; Parke, A.L.; Clifford-Rashotte, M.; Kean, W.F. Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases. Inflammopharmacology, 2015, 23(5), 231-269.
[http://dx.doi.org/10.1007/s10787-015-0239-y] [PMID: 26246395]
[43]
Yao, X.; Ye, F.; Zhang, M.; Cui, C.; Huang, B.; Niu, P.; Liu, X.; Zhao, L.; Dong, E.; Song, C.; Zhan, S.; Lu, R.; Li, H.; Tan, W.; Liu, D. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clin. Infect. Dis., 2020, 71(15), 732-739.
[http://dx.doi.org/10.1093/cid/ciaa237] [PMID: 32150618]
[44]
Lambert, D.W.; Yarski, M.; Warner, F.J.; Thornhill, P.; Parkin, E.T.; Smith, A.I.; Hooper, N.M.; Turner, A.J. Tumor necrosis factor-α 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), 30113-30119.
[http://dx.doi.org/10.1074/jbc.M505111200] [PMID: 15983030]
[45]
Towler, P.; Staker, B.; Prasad, S.G.; Menon, S.; Tang, J.; Parsons, T.; Ryan, D.; Fisher, M.; Williams, D.; Dales, N.A.; Patane, M.A.; Pantoliano, M.W. ACE2 X-ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysis. J. Biol. Chem., 2004, 279(17), 17996-18007.
[http://dx.doi.org/10.1074/jbc.M311191200] [PMID: 14754895]
[46]
Lundin, A.; Dijkman, R.; Bergström, T.; Kann, N.; Adamiak, B.; Hannoun, C.; Kindler, E.; Jónsdóttir, H.R.; Muth, D.; Kint, J.; Forlenza, M.; Müller, M.A.; Drosten, C.; Thiel, V.; Trybala, E. Targeting membrane-bound viral RNA synthesis reveals potent inhibition of diverse coronaviruses including the middle East respiratory syndrome virus. PLoS Pathog., 2014, 10(5), e1004166.
[http://dx.doi.org/10.1371/journal.ppat.1004166] [PMID: 24874215]
[47]
Hoffmann, M.; Kleine-Weber, H.; Schroeder, S.; Krüger, N.; Herrler, T.; Erichsen, S.; Schiergens, T.S.; Herrler, G.; Wu, N.H.; Nitsche, A.; Müller, M.A.; Drosten, C.; Pöhlmann, S. 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]
[48]
Kilianski, A.; Baker, S.C. Cell-based antiviral screening against coronaviruses: developing virus-specific and broad-spectrum inhibitors. Antiviral Res., 2014, 101, 105-112.
[http://dx.doi.org/10.1016/j.antiviral.2013.11.004] [PMID: 24269477]
[49]
Simmons, G.; Gosalia, D.N.; Rennekamp, A.J.; Reeves, J.D.; Diamond, S.L.; Bates, P. Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entry. Proc. Natl. Acad. Sci. USA, 2005, 102(33), 11876-11881.
[http://dx.doi.org/10.1073/pnas.0505577102] [PMID: 16081529]
[50]
van Dongen, M.J.P.; Kadam, R.U.; Juraszek, J.; Lawson, E.; Brandenburg, B.; Schmitz, F.; Schepens, W.B.G.; Stoops, B.; van Diepen, H.A.; Jongeneelen, M.; Tang, C.; Vermond, J.; van Eijgen-Obregoso Real, A.; Blokland, S.; Garg, D.; Yu, W.; Goutier, W.; Lanckacker, E.; Klap, J.M.; Peeters, D.C.G.; Wu, J.; Buyck, C.; Jonckers, T.H.M.; Roymans, D.; Roevens, P.; Vogels, R.; Koudstaal, W.; Friesen, R.H.E.; Raboisson, P.; Dhanak, D.; Goudsmit, J.; Wilson, I.A. A small-molecule fusion inhibitor of influenza virus is orally active in mice. Science, 2019, 363(6431), eaar6221.
[http://dx.doi.org/10.1126/science.aar6221] [PMID: 30846569]
[51]
Frey, G.; Rits-Volloch, S.; Zhang, X.Q.; Schooley, R.T.; Chen, B.; Harrison, S.C. Small molecules that bind the inner core of gp41 and inhibit HIV envelope-mediated fusion. Proc. Natl. Acad. Sci. USA, 2006, 103(38), 13938-13943.
[http://dx.doi.org/10.1073/pnas.0601036103] [PMID: 16963566]
[52]
Yi, L.; Li, Z.; Yuan, K.; Qu, X.; Chen, J.; Wang, G.; Zhang, H.; Luo, H.; Zhu, L.; Jiang, P.; Chen, L.; Shen, Y.; Luo, M.; Zuo, G.; Hu, J.; Duan, D.; Nie, Y.; Shi, X.; Wang, W.; Han, Y.; Li, T.; Liu, Y.; Ding, M.; Deng, H.; Xu, X. Small molecules blocking the entry of severe acute respiratory syndrome coronavirus into host cells. J. Virol., 2004, 78(20), 11334-11339.
[http://dx.doi.org/10.1128/JVI.78.20.11334-11339.2004] [PMID: 15452254]
[53]
Mitsuki, Y.Y.; Ohnishi, K.; Takagi, H.; Oshima, M.; Yamamoto, T.; Mizukoshi, F.; Terahara, K.; Kobayashi, K.; Yamamoto, N.; Yamaoka, S.; Tsunetsugu-Yokota, Y. A single amino acid substitution in the S1 and S2 Spike protein domains determines the neutralization escape phenotype of SARS-CoV. Microbes Infect., 2008, 10(8), 908-915.
[http://dx.doi.org/10.1016/j.micinf.2008.05.009] [PMID: 18606245]
[54]
Kadam, R.U.; Wilson, I.A. Structural basis of influenza virus fusion inhibition by the antiviral drug Arbidol. Proc. Natl. Acad. Sci. USA, 2017, 114(2), 206-214.
[http://dx.doi.org/10.1073/pnas.1617020114] [PMID: 28003465]
[55]
Wang, X.; Cao, R.; Zhang, H.; Liu, J.; Xu, M.; Hu, H.; Li, Y.; Zhao, L.; Li, W.; Sun, X.; Yang, X.; Shi, Z.; Deng, F.; Hu, Z.; Zhong, W.; Wang, M. The anti-influenza virus drug, arbidol is an efficient inhibitor of SARS-CoV-2 in vitro. Cell Discov., 2020, 6(1), 28.
[http://dx.doi.org/10.1038/s41421-020-0169-8] [PMID: 33934117]
[56]
Vankadari, N. Arbidol: A potential antiviral drug for the treatment of SARS-CoV-2 by blocking trimerization of the spike glycoprotein. Int. J. Antimicrob. Agents, 2020, 56(2), 105998.
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105998] [PMID: 32360231]
[57]
Wang, Z; Yang, B; Li, Q; Wen, L; Zhang, R. Clinical features of 69 cases with coronavirus disease 2019 in Wuhan, China. Clin Infect Dis., 2020, 71(15), 769-777.
[http://dx.doi.org/10.1093/cid/ciaa272]
[58]
Wrapp, D.; Wang, N.; Corbett, K.S.; Goldsmith, J.A.; Hsieh, C.L.; Abiona, O.; Graham, B.S.; McLellan, J.S. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science, 2020, 367(6483), 1260-1263.
[http://dx.doi.org/10.1126/science.abb2507] [PMID: 32075877]
[59]
Greenough, T.C.; Babcock, G.J.; Roberts, A.; Hernandez, H.J.; Thomas, W.D., Jr; Coccia, J.A.; Graziano, R.F.; Srinivasan, M.; Lowy, I.; Finberg, R.W.; Subbarao, K.; Vogel, L.; Somasundaran, M.; Luzuriaga, K.; Sullivan, J.L.; Ambrosino, D.M. Development and characterization of a severe acute respiratory syndrome-associated coronavirus-neutralizing human monoclonal antibody that provides effective immunoprophylaxis in mice. J. Infect. Dis., 2005, 191(4), 507-514.
[http://dx.doi.org/10.1086/427242] [PMID: 15655773]
[60]
Zhao, G.; Du, L.; Ma, C.; Li, Y.; Li, L.; Poon, V.K.; Wang, L.; Yu, F.; Zheng, B.J.; Jiang, S.; Zhou, Y. A safe and convenient pseudovirus-based inhibition assay to detect neutralizing antibodies and screen for viral entry inhibitors against the novel human coronavirus MERS-CoV. Virol. J., 2013, 10(1), 266.
[http://dx.doi.org/10.1186/1743-422X-10-266] [PMID: 23978242]
[61]
Bosch, B.J.; Bartelink, W.; Rottier, P.J. Cathepsin L functionally cleaves the severe acute respiratory syndrome coronavirus class I fusion protein upstream of rather than adjacent to the fusion peptide. J. Virol., 2008, 82(17), 8887-8890.
[http://dx.doi.org/10.1128/JVI.00415-08] [PMID: 18562523]
[62]
Sosnowski, P.; Turk, D. Caught in the act: the crystal structure of cleaved cathepsin L bound to the active site of Cathepsin L. FEBS Lett., 2016, 590(8), 1253-1261.
[http://dx.doi.org/10.1002/1873-3468.12140] [PMID: 26992470]
[63]
Zhou, N.; Pan, T.; Zhang, J.; Li, Q.; Zhang, X.; Bai, C.; Huang, F.; Peng, T.; Zhang, J.; Liu, C.; Tao, L.; Zhang, H. Glycopeptide antibiotics potently inhibit cathepsin L in the late endosome/lysosome and block the entry of Ebola virus, Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus (SARS-CoV). J. Biol. Chem., 2016, 291(17), 9218-9232.
[http://dx.doi.org/10.1074/jbc.M116.716100] [PMID: 26953343]
[64]
Zhang, J.; Ma, X.; Yu, F.; Liu, J.; Zou, F.; Pan, T.; Zhang, H Teicoplanin potently blocks the cell entry of 2019-nCoV bioRxiv, 2020, 02.05.935387.
[http://dx.doi.org/10.1101/2020.02.05.935387]
[65]
Zhou, Y.; Vedantham, P.; Lu, K.; Agudelo, J.; Carrion, R., Jr; Nunneley, J.W.; Barnard, D.; Pöhlmann, S.; McKerrow, J.H.; Renslo, A.R.; Simmons, G. 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]
[66]
Shah, P.P.; Wang, T.; Kaletsky, R.L.; Myers, M.C.; Purvis, J.E.; Jing, H.; Huryn, D.M.; Greenbaum, D.C.; Smith, A.B., III; Bates, P.; Diamond, S.L. A small-molecule oxocarbazate inhibitor of human cathepsin L blocks severe acute respiratory syndrome and ebola pseudotype virus infection into human embryonic kidney 293T cells. Mol. Pharmacol., 2010, 78(2), 319-324.
[http://dx.doi.org/10.1124/mol.110.064261] [PMID: 20466822]
[67]
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), 6537-6545.
[http://dx.doi.org/10.1128/JVI.00094-12] [PMID: 22496216]
[68]
Millet, J.K.; Whittaker, G.R. Host cell entry of Middle East respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein. Proc. Natl. Acad. Sci. USA, 2014, 111(42), 15214-15219.
[http://dx.doi.org/10.1073/pnas.1407087111] [PMID: 25288733]
[69]
Swinney, D.C. Phenotypic vs. target-based drug discovery for first-in-class medicines. Clin. Pharmacol. Ther., 2013, 93(4), 299-301.
[http://dx.doi.org/10.1038/clpt.2012.236] [PMID: 23511784]
[70]
Wu, G.; Zhao, T.; Kang, D.; Zhang, J.; Song, Y.; Namasivayam, V.; Kongsted, J.; Pannecouque, C.; De Clercq, E.; Poongavanam, V.; Liu, X.; Zhan, P. Overview of recent strategic advances in medicinal chemistry. J. Med. Chem., 2019, 62(21), 9375-9414.
[http://dx.doi.org/10.1021/acs.jmedchem.9b00359] [PMID: 31050421]
[71]
Du, J.; Guo, J.; Kang, D.; Li, Z.; Wang, G.; Wu, J.; Zhang, Z.; Fang, H.; Hou, X.; Huang, Z.; Li, G.; Lu, X.; Liu, X.; Ouyang, L.; Rao, L.; Zhan, P.; Zhang, X.; Zhan, Y. New techniques and strategies in drug discovery. Chin. Chem. Lett., 2020, 31(7), 1695-1708.
[http://dx.doi.org/10.1016/j.cclet.2020.03.028]
[72]
Cherian, S.S.; Agrawal, M.; Basu, A.; Abraham, P.; Gangakhedkar, R.R.; Bhargava, B. Perspectives for repurposing drugs for the coronavirus disease 2019. Indian J. Med. Res., 2020, 151(2 & 3), 160-171.
[PMID: 32317408]
[73]
Liu, Q.; Xia, S.; Sun, Z.; Wang, Q.; Du, L.; Lu, L.; Jiang, S. Testing of Middle East respiratory syndrome coronavirus replication inhibitors for the ability to block viral entry. Antimicrob. Agents Chemother., 2015, 59(1), 742-744.
[http://dx.doi.org/10.1128/AAC.03977-14] [PMID: 25331705]
[74]
Sisk, J.M.; Frieman, M.B.; Machamer, C.E. Coronavirus S protein-induced fusion is blocked prior to hemifusion by Abl kinase inhibitors. J. Gen. Virol., 2018, 99(5), 619-630.
[http://dx.doi.org/10.1099/jgv.0.001047] [PMID: 29557770]
[75]
Coleman, C.M.; Sisk, J.M.; Mingo, R.M.; Nelson, E.A.; White, J.M.; Frieman, M.B. Abelson kinase inhibitors are potent inhibitors of severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus fusion. J. Virol., 2016, 90(19), 8924-8933.
[http://dx.doi.org/10.1128/JVI.01429-16] [PMID: 27466418]
[76]
Dyall, J.; Coleman, C.M.; Hart, B.J.; Venkataraman, T.; Holbrook, M.R.; Kindrachuk, J.; Johnson, R.F.; Olinger, G.G., Jr; Jahrling, P.B.; Laidlaw, M.; Johansen, L.M.; Lear-Rooney, C.M.; Glass, P.J.; Hensley, L.E.; Frieman, M.B. Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection. Antimicrob. Agents Chemother., 2014, 58(8), 4885-4893.
[http://dx.doi.org/10.1128/AAC.03036-14] [PMID: 24841273]
[77]
Shin, J.S.; Jung, E.; Kim, M.; Baric, R.S.; Go, Y.Y. Saracatinib inhibits middle east respiratory syndrome-coronavirus replication in vitro. Viruses, 2018, 10(6), 283.
[http://dx.doi.org/10.3390/v10060283] [PMID: 29795047]
[78]
Islam, M.T.; Sarkar, C.; El-Kersh, D.M.; Jamaddar, S.; Uddin, S.J.; Shilpi, J.A.; Mubarak, M.S. Natural products and their derivatives against coronavirus: A review of the non- clinical and pre-clinical data. Phytother. Res., 2020, 34(10), 2471-2492.
[http://dx.doi.org/10.1002/ptr.6700] [PMID: 32248575]
[79]
Ho, T.Y.; Wu, S.L.; Chen, J.C.; Li, C.C.; Hsiang, C.Y. Emodin blocks the SARS coronavirus spike protein and angiotensin-converting enzyme 2 interaction. Antiviral Res., 2007, 74(2), 92-101.
[http://dx.doi.org/10.1016/j.antiviral.2006.04.014] [PMID: 16730806]
[80]
Rabaan, A.A.; Al-Ahmed, S.H.; Haque, S.; Sah, R.; Tiwari, R.; Malik, Y.S.; Dhama, K.; Yatoo, M.I.; Bonilla-Aldana, D.K.; Rodriguez-Morales, A.J. SARS-CoV-2, SARS-CoV, and MERS-COV: A comparative overview. Infez. Med., 2020, 28(2), 174-184.
[PMID: 32275259]
[81]
Walls, A.C.; Park, Y.J.; Tortorici, M.A.; Wall, A.; McGuire, A.T.; Veesler, D. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell, 2020, 183(6), 1735.
[http://dx.doi.org/10.1016/j.cell.2020.11.032] [PMID: 33306958]
[82]
Huang, Y.; Yang, C.; Xu, X.F.; Xu, W.; Liu, S.W. 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.
[http://dx.doi.org/10.1038/s41401-020-0485-4] [PMID: 32747721]
[83]
Liu, S.; Xiao, G.; Chen, Y.; He, Y.; Niu, J.; Escalante, C.R.; Xiong, H.; Farmar, J.; Debnath, A.K.; Tien, P.; Jiang, S. Interaction between heptad repeat 1 and 2 regions in spike protein of SARS-associated coronavirus: implications for virus fusogenic mechanism and identification of fusion inhibitors. Lancet, 2004, 363(9413), 938-947.
[http://dx.doi.org/10.1016/S0140-6736(04)15788-7] [PMID: 15043961]

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