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Letters in Drug Design & Discovery

Author(s): Yee Siew Choong*, Theam Soon Lim, Hanyun Liu, Rubin Jiang, Zimu Cai and Yuan Ge*

DOI: 10.2174/1570180817999201104123750

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Potential Inhibition of COVID-19 RNA-dependent RNA Polymerase by Hepatitis C Virus Non-nucleoside Inhibitors: An In-silico Perspective

Page: [429 - 435] Pages: 7

  • * (Excluding Mailing and Handling)

Abstract

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a novel member of the genus betacoronavirus in the Coronaviridae family. It has been identified as the causative agent of coronavirus disease 2019 (COVID-19), spreading rapidly in Asia, America and Europe. Like some other RNA viruses, RNA replication and transcription of SARS-CoV-2 rely on its RNA-dependent RNA polymerase (RdRP), which is a therapeutic target of clinical importance. Crystal structure of SARS-CoV-2 was solved recently (PDB ID 6M71) with some missing residues.

Objective: We used SARS-CoV-2 RdRP as a target protein to screen for possible chemical molecules with potential anti-viral effects.

Methods: Here we modelled the missing residues 896-905 via homology modelling and then analysed the interactions of Hepatitis C virus allosteric non-nucleoside inhibitors (NNIs) in the reported NNIs binding sites in SARS-CoV-2 RdRP.

Results: We found that MK-3281, filibuvir, setrobuvir and dasabuvir might be able to inhibit SARS-CoV-2 RdRP based on their binding affinities in the respective binding sites.

Conclusion: Further in vitro and in vivo experimental research will be carried out to evaluate their effectiveness in COVID-19 treatment in the near future.

Keywords: SARS-CoV-2, COVID-19, RNA-dependent RNA polymerase, docking simulation, binding sites, allosteric nonnucleoside inhibitors.

Graphical Abstract

[1]
Zhu, N.; Zhang, D.; Wang, W.; Li, X.; Yang, B.; Song, J.; Zhao, X.; Huang, B.; Shi, W.; Lu, R.; Niu, P.; Zhan, F.; Ma, X.; Wang, D.; Xu, W.; Wu, G.; Gao, G.F.; Tan, W. China Novel Coronavirus Investigating and Research Team. A novel coronavirus from patients with pneumonia in China, 2019. N. Engl. J. Med., 2020, 382(8), 727-733.
[http://dx.doi.org/10.1056/NEJMoa2001017] [PMID: 31978945]
[2]
Lu, R.; Zhao, X.; Li, J.; Niu, P.; Yang, B.; Wu, H.; Wang, W.; Song, H.; Huang, B.; Zhu, N.; Bi, Y.; Ma, X.; Zhan, F.; Wang, L.; Hu, T.; Zhou, H.; Hu, Z.; Zhou, W.; Zhao, L.; Chen, J.; Meng, Y.; Wang, J.; Lin, Y.; Yuan, J.; Xie, Z.; Ma, J.; Liu, W.J.; Wang, D.; Xu, W.; Holmes, E.C.; Gao, G.F.; Wu, G.; Chen, W.; Shi, W.; Tan, W. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet, 2020, 395(10224), 565-574.
[http://dx.doi.org/10.1016/S0140-6736(20)30251-8] [PMID: 32007145]
[3]
Sawicki, S.G.; Sawicki, D.L.; Younker, D.; Meyer, Y.; Thiel, V.; Stokes, H.; Siddell, S.G. Functional and genetic analysis of coronavirus replicase-transcriptase proteins. PLoS Pathog., 2005, 1(4), e39.
[http://dx.doi.org/10.1371/journal.ppat.0010039] [PMID: 16341254]
[4]
Ziebuhr, J.; Snijder, E.J.; Gorbalenya, A.E. Virus-encoded proteinases and proteolytic processing in the Nidovirales. J. Gen. Virol., 2000, 81(Pt 4), 853-879.
[http://dx.doi.org/10.1099/0022-1317-81-4-853] [PMID: 10725411]
[5]
Oh, J.W.; Sheu, G.T.; Lai, M.M. Template requirement and initiation site selection by hepatitis C virus polymerase on a minimal viral RNA template. J. Biol. Chem., 2000, 275(23), 17710-17717.
[http://dx.doi.org/10.1074/jbc.M908781199] [PMID: 10749880]
[6]
Bruenn, J.A. A structural and primary sequence comparison of the viral RNA-dependent RNA polymerases. Nucleic Acids Res., 2003, 31(7), 1821-1829.
[http://dx.doi.org/10.1093/nar/gkg277] [PMID: 12654997]
[7]
Ferrer-Orta, C.; Arias, A.; Escarmís, C.; Verdaguer, N. A comparison of viral RNA-dependent RNA polymerases. Curr. Opin. Struct. Biol., 2006, 16(1), 27-34.
[http://dx.doi.org/10.1016/j.sbi.2005.12.002] [PMID: 16364629]
[8]
Ng, K.K.; Arnold, J.J.; Cameron, C.E. Structure-function relationships among RNA-dependent RNA polymerases. Curr. Top. Microbiol. Immunol., 2008, 320, 137-156.
[http://dx.doi.org/10.1007/978-3-540-75157-1_7] [PMID: 18268843]
[9]
te Velthuis, A.J.W. Common and unique features of viral RNA-dependent polymerases. Cell. Mol. Life Sci., 2014, 71(22), 4403-4420.
[http://dx.doi.org/10.1007/s00018-014-1695-z] [PMID: 25080879]
[10]
Boerner, J.E.; Lyle, J.M.; Daijogo, S.; Semler, B.L.; Schultz, S.C.; Kirkegaard, K.; Richards, O.C. Allosteric effects of ligands and mutations on poliovirus RNA-dependent RNA polymerase. J. Virol., 2005, 79(12), 7803-7811.
[http://dx.doi.org/10.1128/JVI.79.12.7803-7811.2005] [PMID: 15919933]
[11]
Deore, R.R.; Chern, J.W. NS5B RNA dependent RNA polymerase inhibitors: the promising approach to treat hepatitis C virus infections. Curr. Med. Chem., 2010, 17(32), 3806-3826.
[http://dx.doi.org/10.2174/092986710793205471] [PMID: 20858218]
[12]
Eltahla, A.A.; Luciani, F.; White, P.A.; Lloyd, A.R.; Bull, R.A. Inhibitors of the hepatitis C virus polymerase; mode of action and resistance. Viruses, 2015, 7(10), 5206-5224.
[http://dx.doi.org/10.3390/v7102868] [PMID: 26426038]
[13]
Shimizu, H.; Saito, A.; Mikuni, J.; Nakayama, E.E.; Koyama, H.; Honma, T.; Shirouzu, M.; Sekine, S.I.; Shioda, T. Discovery of a small molecule inhibitor targeting dengue virus NS5 RNA-dependent RNA polymerase. PLoS Negl. Trop. Dis., 2019, 13(11), e0007894.
[http://dx.doi.org/10.1371/journal.pntd.0007894] [PMID: 31738758]
[14]
Powdrill, M.H.; Bernatchez, J.A.; Götte, M. Inhibitors of the hepatitis C virus RNA-dependent RNA polymerase NS5B. Viruses, 2010, 2(10), 2169-2195.
[http://dx.doi.org/10.3390/v2102169] [PMID: 21994615]
[15]
Dong, L.; Hu, S.; Gao, J. Discovering drugs to treat coronavirus disease 2019 (COVID-19). Drug Discov. Ther., 2020, 14(1), 58-60.
[http://dx.doi.org/10.5582/ddt.2020.01012] [PMID: 32147628]
[16]
Elfiky, A.A. SARS-CoV-2 RNA dependent RNA polymerase (RdRp) targeting: an in silico perspective. J. Biomol. Struct. Dyn., 2020, 6, 1-9.
[http://dx.doi.org/10.1080/07391102.2020.1761882] [PMID: 32338164]
[17]
Elfiky, A.A. Anti-HCV, nucleotide inhibitors, repurposing against COVID-19. Life Sci., 2020, 248, 117477.
[http://dx.doi.org/10.1016/j.lfs.2020.117477] [PMID: 32119961]
[18]
Elfiky, A.A. Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): A molecular docking study. Life Sci., 2020, •••, 253117592.
[http://dx.doi.org/10.1016/j.lfs.2020.117592] [PMID: 32222463]
[19]
Shah, B.; Modi, P.; Sagar, S.R. In silico studies on therapeutic agents for COVID-19: Drug repurposing approach. Life Sci., 2020, •••, 252117652.
[http://dx.doi.org/10.1016/j.lfs.2020.117652] [PMID: 32278693]
[20]
Gao, Y.; Yan, L.; Huang, Y.; Liu, F.; Zhao, Y.; Cao, L.; Wang, T.; Sun, Q.; Ming, Z.; Zhang, L.; Ge, J.; Zheng, L.; Zhang, Y.; Wang, H.; Zhu, Y.; Zhu, C.; Hu, T.; Hua, T.; Zhang, B.; Yang, X.; Li, J.; Yang, H.; Liu, Z.; Xu, W.; Guddat, L.W.; Wang, Q.; Lou, Z.; Rao, Z. Structure of the RNA-dependent RNA polymerase from COVID-19 virus. Science, 2020, 368(6492), 779-782.
[http://dx.doi.org/10.1126/science.abb7498] [PMID: 32277040]
[21]
Sali, A.; Blundell, T.L. Comparative protein modelling by satisfaction of spatial restraints. J. Mol. Biol., 1993, 234(3), 779-815.
[http://dx.doi.org/10.1006/jmbi.1993.1626] [PMID: 8254673]
[22]
Hanwell, M.D.; Curtis, D.E.; Lonie, D.C.; Vandermeersch, T.; Zurek, E.; Hutchison, G.R. Avogadro: an advanced semantic chemical editor, visualization, and analysis platform. J. Cheminform., 2012, 4(1), 17.
[http://dx.doi.org/10.1186/1758-2946-4-17] [PMID: 22889332]
[23]
Morris, G.M.; Huey, R.; Lindstrom, W.; Sanner, M.F.; Belew, R.K.; Goodsell, D.S.; Olson, A.J. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J. Comput. Chem., 2009, 30(16), 2785-2791.
[http://dx.doi.org/10.1002/jcc.21256] [PMID: 19399780]
[24]
Di Marco, S.; Volpari, C.; Tomei, L.; Altamura, S.; Harper, S.; Narjes, F.; Koch, U.; Rowley, M.; De Francesco, R.; Migliaccio, G.; Carfí, A. Interdomain communication in hepatitis C virus polymerase abolished by small molecule inhibitors bound to a novel allosteric site. J. Biol. Chem., 2005, 280(33), 29765-29770.
[http://dx.doi.org/10.1074/jbc.M505423200] [PMID: 15955819]
[25]
Love, R.A.; Parge, H.E.; Yu, X.; Hickey, M.J.; Diehl, W.; Gao, J.; Wriggers, H.; Ekker, A.; Wang, L.; Thomson, J.A.; Dragovich, P.S.; Fuhrman, S.A. Crystallographic identification of a noncompetitive inhibitor binding site on the hepatitis C virus NS5B RNA polymerase enzyme. J. Virol., 2003, 77(13), 7575-7581.
[http://dx.doi.org/10.1128/JVI.77.13.7575-7581.2003] [PMID: 12805457]
[26]
Pfefferkorn, J.A.; Greene, M.L.; Nugent, R.A.; Gross, R.J.; Mitchell, M.A.; Finzel, B.C.; Harris, M.S.; Wells, P.A.; Shelly, J.A.; Anstadt, R.A.; Kilkuskie, R.E.; Kopta, L.A.; Schwende, F.J. Inhibitors of HCV NS5B polymerase. Part 1: Evaluation of the southern region of (2Z)-2-(benzoylamino)-3-(5-phenyl-2-furyl)acrylic acid. Bioorg. Med. Chem. Lett., 2005, 15(10), 2481-2486.
[http://dx.doi.org/10.1016/j.bmcl.2005.03.066] [PMID: 15863301]
[27]
Hang, J.Q.; Yang, Y.; Harris, S.F.; Leveque, V.; Whittington, H.J.; Rajyaguru, S.; Ao-Ieong, G.; McCown, M.F.; Wong, A.; Giannetti, A.M.; Le Pogam, S.; Talamás, F.; Cammack, N.; Nájera, I.; Klumpp, K. Slow binding inhibition and mechanism of resistance of non-nucleoside polymerase inhibitors of hepatitis C virus. J. Biol. Chem., 2009, 284(23), 15517-15529.
[http://dx.doi.org/10.1074/jbc.M808889200] [PMID: 19246450]
[28]
Morris, G.M.; Goodsell, D.S.; Halliday, R.S.; Huey, R.; Hart, W.E.; Belew, R.K.; Olson, A.J. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J. Comput. Chem., 1998, 19, 1639-1662.
[http://dx.doi.org/10.1002/(SICI)1096-987X(19981115)19:14<1639:AID-JCC10>3.0.CO;2-B]
[29]
DeLano, W.L. PyMOL: An open-source molecular graphics tool. CCP4 Newslett. Protein Crystallogr., 2002, 40, 82-92.
[30]
Narjes, F.; Crescenzi, B.; Ferrara, M.; Habermann, J.; Colarusso, S. Ferreira, Mdel.R.; Stansfield, I.; Mackay, A.C.; Conte, I.; Ercolani, C.; Zaramella, S.; Palumbi, M.C.; Meuleman, P.; Leroux-Roels, G.; Giuliano, C.; Fiore, F.; Di Marco, S.; Baiocco, P.; Koch, U.; Migliaccio, G.; Altamura, S.; Laufer, R.; De Francesco, R.; Rowley, M. Discovery of (7R)-14-cyclohexyl-7-[2-(dimethylamino)ethyl](methyl) amino-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylic acid (MK-3281), a potent and orally bioavailable finger-loop inhibitor of the hepatitis C virus NS5B polymerase. J. Med. Chem., 2011, 54(1), 289-301.
[http://dx.doi.org/10.1021/jm1013105] [PMID: 21141896]
[31]
Beaulieu, P.L.; Coulombe, R.; Duan, J.; Fazal, G.; Godbout, C.; Hucke, O.; Jakalian, A.; Joly, M.A.; Lepage, O.; Llinàs-Brunet, M.; Naud, J.; Poirier, M.; Rioux, N.; Thavonekham, B.; Kukolj, G.; Stammers, T.A. Structure-based design of novel HCV NS5B thumb pocket 2 allosteric inhibitors with submicromolar gt1 replicon potency: Discovery of a quinazolinone chemotype. Bioorg. Med. Chem. Lett., 2013, 23(14), 4132-4140.
[http://dx.doi.org/10.1016/j.bmcl.2013.05.037] [PMID: 23768906]
[32]
Hirashima, S.; Suzuki, T.; Ishida, T.; Noji, S.; Yata, S.; Ando, I.; Komatsu, M.; Ikeda, S.; Hashimoto, H. Benzimidazole derivatives bearing substituted biphenyls as hepatitis C virus NS5B RNA-dependent RNA polymerase inhibitors: Structure-activity relationship studies and identification of a potent and highly selective inhibitor JTK-109. J. Med. Chem., 2006, 49(15), 4721-4736.
[http://dx.doi.org/10.1021/jm060269e] [PMID: 16854079]
[33]
Beaulieu, P.L.; Bös, M.; Cordingley, M.G.; Chabot, C.; Fazal, G.; Garneau, M.; Gillard, J.R.; Jolicoeur, E.; LaPlante, S.; McKercher, G.; Poirier, M.; Poupart, M.A.; Tsantrizos, Y.S.; Duan, J.; Kukolj, G. Discovery of the first thumb pocket 1 NS5B polymerase inhibitor (BILB 1941) with demonstrated antiviral activity in patients chronically infected with genotype 1 hepatitis C virus (HCV). J. Med. Chem., 2012, 55(17), 7650-7666.
[http://dx.doi.org/10.1021/jm3006788] [PMID: 22849725]
[34]
Gentles, R.G.; Ding, M.; Bender, J.A.; Bergstrom, C.P.; Grant-Young, K.; Hewawasam, P.; Hudyma, T.; Martin, S.; Nickel, A.; Regueiro-Ren, A.; Tu, Y.; Yang, Z.; Yeung, K.S.; Zheng, X.; Chao, S.; Sun, J.H.; Beno, B.R.; Camac, D.M.; Chang, C.H.; Gao, M.; Morin, P.E.; Sheriff, S.; Tredup, J.; Wan, J.; Witmer, M.R.; Xie, D.; Hanumegowda, U.; Knipe, J.; Mosure, K.; Santone, K.S.; Parker, D.D.; Zhuo, X.; Lemm, J.; Liu, M.; Pelosi, L.; Rigat, K.; Voss, S.; Wang, Y.; Wang, Y.K.; Colonno, R.J.; Gao, M.; Roberts, S.B.; Gao, Q.; Ng, A.; Meanwell, N.A.; Kadow, J.F. Discovery and preclinical characterization of the cyclopropylindolobenzazepine BMS-791325, a potent allosteric inhibitor of the hepatitis C virus NS5B polymerase. J. Med. Chem., 2014, 57(5), 1855-1879.
[http://dx.doi.org/10.1021/jm4016894] [PMID: 24397558]
[35]
Raboisson, P.; de Kock, H.; Rosenquist, A.; Nilsson, M.; Salvador-Oden, L.; Lin, T.I.; Roue, N.; Ivanov, V.; Wähling, H.; Wickström, K.; Hamelink, E.; Edlund, M.; Vrang, L.; Vendeville, S.; Van de Vreken, W.; McGowan, D.; Tahri, A.; Hu, L.; Boutton, C.; Lenz, O.; Delouvroy, F.; Pille, G.; Surleraux, D.; Wigerinck, P.; Samuelsson, B.; Simmen, K. Structure-activity relationship study on a novel series of cyclopentane-containing macrocyclic inhibitors of the hepatitis C virus NS3/4A protease leading to the discovery of TMC435350. Bioorg. Med. Chem. Lett., 2008, 18(17), 4853-4858.
[http://dx.doi.org/10.1016/j.bmcl.2008.07.088] [PMID: 18678486]
[36]
Jacobson, I.; Pockros, P.; Lalezari, J.; Lawitz, E.; Rodriguez-Torres, M.; DeJesus, E.; Haas, F.; Martorell, C.; Pruitt, R.; Durham, K.; Srinivasan, S.; Rosario, M.; Jagannatha, S.; Hammond, J. Antiviral activity of filibuvir in combination with pegylated interferon alfa-2a and ribavirin for 28 days in treatment naive patients chronically infected with HCV genotype 1. J. Hepatol., 2009, 50, S382-S383.
[http://dx.doi.org/10.1016/S0168-8278(09)61054-0]
[37]
Proulx, L.; Bourgault, B.; Chauret, N.; Larouche, R.; Tanguay, M.; Thibert, R. Results of a safety, tolerability and pharmacokinetic phase I study of VCH-916, a novel polymerase inhibitor for HCV, following single ascending doses in healthy volunteers. J. Hepatol., 2008, 48, S320-S321.
[http://dx.doi.org/10.1016/S0168-8278(08)60856-9]
[38]
Cooper, C.; Lawitz, E.J.; Ghali, P.; Rodriguez-Torres, M.; Anderson, F.H.; Lee, S.S.; Bédard, J.; Chauret, N.; Thibert, R.; Boivin, I.; Nicolas, O.; Proulx, L. Evaluation of VCH-759 monotherapy in hepatitis C infection. J. Hepatol., 2009, 51(1), 39-46.
[http://dx.doi.org/10.1016/j.jhep.2009.03.015] [PMID: 19446909]
[39]
Lawitz, E.; Rodriguez-Torres, M.; DeMicco, M.; Nguyen, T.; Godofsky, E.; Appleman, J.; Rahimy, M.; Crowley, C.; Freddo, J. Antiviral activity of ANA598, a potent non-nucleoside polymerase inhibitor, in chronic hepatitis C patients. J. Hepatol., 2009, 50, S384.
[http://dx.doi.org/10.1016/S0168-8278(09)61057-6]
[40]
Gray, F.; Amphlett, E.; Bright, H.; Chambers, L.; Cheasty, A.; Fenwick, R.; Haigh, D.; Hartley, D.; Howes, P.; Jarvest, R.; Mirzai, F.; Nerozzi, F.; Parry, N.; Slater, M.; Smith, S.; Thommes, P.; Wilkinson, C.; Williams, E. GSK625433; A novel and highly potent inhibitor of the HCV NS5B polymerase. J. Hepatol., 2007, 46, S225.
[http://dx.doi.org/10.1016/S0168-8278(07)62192-8]
[41]
Paparin, J.L.; Amador, A.; Badaroux, E.; Bot, S.; Caillet, C.; Convard, T.; Da Costa, D.; Dukhan, D.; Griffe, L.; Griffon, J.F.; LaColla, M.; Leroy, F.; Liuzzi, M.; Giulia Loi, A.; McCarville, J.; Mascia, V.; Milhau, J.; Onidi, L.; Pierra, C.; Rahali, R.; Rosinosky, E.; Sais, E.; Seifer, M.; Surleraux, D.; Standring, D.; Dousson, C.B. Discovery of benzophosphadiazine drug candidate IDX375: A novel hepatitis C allosteric NS5B RdRp inhibitor. Bioorg. Med. Chem. Lett., 2017, 27(11), 2634-2640.
[http://dx.doi.org/10.1016/j.bmcl.2017.01.017] [PMID: 28416131]
[42]
Poordad, F.; Lawitz, E.; DeJesus, E.; Kowdley, K.V.; Gaultier, I.; Cohen, D.E.; Xie, W.; Larsen, L.; Pilot-Matias, T.; Koev, G.; Dumas, D.; Podsadecki, T.; Bernstein, B. ABT-072 or ABT-333 combined with pegylated interferon/ribavirin after 3-day monotherapy in HVN genotype 1 (GT1)-infected treatment-naive subjects: 12-week sustained virologic response (SVR12) and safety results. J. Hepatol., 2012, 56, S478.
[http://dx.doi.org/10.1016/S0168-8278(12)61218-5]
[43]
Shih, I.H.; Vliegen, I.; Peng, B.; Yang, H.; Hebner, C.; Paeshuyse, J.; Pürstinger, G.; Fenaux, M.; Tian, Y.; Mabery, E.; Qi, X.; Bahador, G.; Paulson, M.; Lehman, L.S.; Bondy, S.; Tse, W.; Reiser, H.; Lee, W.A.; Schmitz, U.; Neyts, J.; Zhong, W. Mechanistic characterization of GS-9190 (Tegobuvir), a novel nonnucleoside inhibitor of hepatitis C virus NS5B polymerase. Antimicrob. Agents Chemother., 2011, 55(9), 4196-4203.
[http://dx.doi.org/10.1128/AAC.00307-11] [PMID: 21746939]
[44]
Wallace, A.C.; Laskowski, R.A.; Thornton, J.M. LIGPLOT: A program to generate schematic diagrams of protein-ligand interactions. Protein Eng., 1995, 8(2), 127-134.
[http://dx.doi.org/10.1093/protein/8.2.127] [PMID: 7630882]
[45]
Babadaei, M.M.N.; Hasan, A.; Vahdani, Y.; Bloukh, S.H.; Sharifi, M.; Kachooei, E.; Haghighat, S.; Falahati, M. Development of remdesivir repositioning as a nucleotide analog against COVID-19 RNA dependent RNA polymerase. J. Biomol. Struct. Dyn., 2020, 20, 1-9.
[http://dx.doi.org/10.1080/07391102.2020.1767210] [PMID: 32397906]
[46]
Chien, M.; Anderson, T.K.; Jockusch, S.; Tao, C.; Li, X.; Kumar, S.; Russo, J.J.; Kirchdoerfer, R.N.; Ju, J. Nucleotide analogues as inhibitors of SARS-CoV-2 polymerase, a key drug target for COVID-19. J. Proteome Res., 2020, 19(11), 4690-4697.
[http://dx.doi.org/10.1021/acs.jproteome.0c00392] [PMID: 32692185]
[47]
Sayad, B.; Sobhani, M.; Khodarahmi, R. BSobhani, M.; Khodarahmi, R. Sofosbuvir as repurposed antiviral drug against COVID-19: Why were we convinced to evaluate the drug in a registered/approved clinical trial? Arch. Med. Res., 2020, 51(6), 577-581.
[http://dx.doi.org/10.1016/j.arcmed.2020.04.018] [PMID: 32387040]
[48]
Alexpandi, R.; De Mesquita, J.F.; Pandian, S.K.; Ravi, A.V. Quinolines-based SARS-CoV-2 3CLpro and RdRp inhibitors and spike-RBD-ACE2 inhibitor for drug-repurposing against COVID-19: An in silico analysis. Front. Microbiol., 2020, 11, 1796.
[http://dx.doi.org/10.3389/fmicb.2020.01796] [PMID: 32793181]
[49]
Zhu, W.; Chen, C.Z.; Gorshkov, K.; Xu, M.; Lo, D.C.; Zheng, W. RNA-dependent RNA polymerase as a target for COVID-19 drug discovery. SLAS Discov., 2020, 25(10), 1141-1151.
[http://dx.doi.org/10.1177/247255522094212] [PMID: 32660307]
[50]
McKee, D.L.; Sternberg, A.; Stange, U.; Laufer, S.; Naujokat, C. Candidate drugs against SARS-CoV-2 and COVID-19. Pharmacol. Res., 2020, 157, 104859.
[http://dx.doi.org/10.1016/j.phrs.2020.104859] [PMID: 32360480]
[51]
Singh, S.; Sk, M.F.; Sonawane, A.; Kar, P.; Sadhukhan, S. Plant-derived natural polyphenols as potential antiviral drugs against SARS-CoV-2 via RNA-dependent RNA polymerase (RdRp) inhibition: an in-silico analysis. J. Biomol. Struct. Dyn., 2020, •••, 1-16.
[http://dx.doi.org/10.1080/07391102.2020.1796810] [PMID: 32720577]
[52]
Aktaş, A.; Tüzün, B.; Aslan, R.; Sayin, K.; Ataseven, H. New anti-viral drugs for the treatment of COVID-19 instead of favipiravir. J. Biomol. Struct. Dyn., 2020, 12, 1-11.
[http://dx.doi.org/10.1080/07391102.2020.1806112] [PMID: 32783586]
[53]
Huang, J.; Song, W.; Huang, H.; Sun, Q. Pharmacological therapeutics targeting RNA-dependent RNA polymerase, proteinase and spike protein: From mechanistic studies to clinical trials for COVID-19. J. Clin. Med., 2020, 9(4), E1131.
[http://dx.doi.org/10.3390/jcm9041131] [PMID: 32326602]
[54]
Delang, L.; Coelmont, L.; Neyts, J. Antiviral therapy for hepatitis C virus: beyond the standard of care. Viruses, 2010, 2(4), 826-866.
[http://dx.doi.org/10.3390/v2040826] [PMID: 21994657]