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Current Pharmaceutical Biotechnology

Editor-in-Chief

ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

Review Article

Promising Repurposed Antiviral Molecules to Combat SARS-CoV-2: A Review

Author(s): Yashumati Ratan, Aishwarya Rajput, Vivek Jain, Dinesh Kumar Mishra, Rupesh Kumar Gautam* and Ashutosh Pareek*

Volume 24, Issue 14, 2023

Published on: 18 April, 2023

Page: [1727 - 1739] Pages: 13

DOI: 10.2174/1389201024666230302113110

Price: $65

Open Access Journals Promotions 2
Abstract

COVID-19, an extremely transmissible and pathogenic viral disease, triggered a global pandemic that claimed lives worldwide. To date, there is no clear and fully effective treatment for COVID-19 disease. Nevertheless, the urgency to discover treatments that can turn the tide has led to the development of a variety of preclinical drugs that are potential candidates for probative results. Although most of these supplementary drugs are constantly being tested in clinical trials against COVID-19, recognized organizations have aimed to outline the prospects in which their use could be considered. A narrative assessment of current articles on COVID-19 disease and its therapeutic regulation was performed. This review outlines the use of various potential treatments against SARS-CoV-2, categorized as fusion inhibitors, protease inhibitors, and RNA-dependent RNA polymerase inhibitors, which include antiviral drugs such as Umifenovir, Baricitinib, Camostatmesylate, Nafamostatmesylate, Kaletra, Paxlovide, Darunavir, Atazanavir, Remdesivir, Molnupiravir, Favipiravir, and Ribavirin. To understand the virology of SARS-CoV-2, potential therapeutic approaches for the treatment of COVID-19 disease, synthetic methods of potent drug candidates, and their mechanisms of action have been addressed in this review. It intends to help readers approach the accessible statistics on the helpful treatment strategies for COVID-19 disease and to serve as a valuable resource for future research in this area.

Keywords: COVID-19, SARS-CoV-2, COVID-19 treatment, coronavirus, corona treatment, antiviral molecules.

Graphical Abstract
[1]
Ahmed, S.S. The coronavirus disease 2019 (COVID-19): A review. J. Adv. Med. Med. Res., 2020, 32(4), 1-9.
[http://dx.doi.org/10.9734/jammr/2020/v32i430393]
[2]
Lou, J.; Tian, S.J.; Niu, S.M.; Kang, X.Q.; Lian, H.X.; Zhang, L.X.; Zhang, J.J. Coronavirus disease 2019: A bibliometric analysis and review. Eur. Rev. Med. Pharmacol. Sci., 2020, 24(6), 3411-3421.
[http://dx.doi.org/10.26355/eurrev_202003_20712] [PMID: 32271460]
[3]
Coronavirus disease - 2019 (COVID-19). WHO situation report-94, 2020. Available from: https://www.who.int/publications-detail/infection-prevention-and-control-during-health-care-when-novel-coronavirus-(NCoV)-
[4]
Wang, H.; Li, X.; Li, T.; Zhang, S.; Wang, L.; Wu, X.; Liu, J. The genetic sequence, origin, and diagnosis of SARS-CoV-2. Eur. J. Clin. Microbiol. Infect. Dis., 2020, 39(9), 1629-1635.
[http://dx.doi.org/10.1007/s10096-020-03899-4] [PMID: 32333222]
[5]
European Centre for Disease Prevention and Control. Cluster of Pneumonia Cases Caused by a Novel Coronavirus Wuhan, China. 2020. Available from: https://www.ecdc.europa.eu/sites/default/files/documents/Risk assessment - pneumonia Wuhan China January 17 2020.pdf
[6]
Bchetnia, M.; Girard, C.; Duchaine, C.; Laprise, C. The outbreak of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): A review of the current global status. J. Infect. Public Health, 2020, 13(11), 1601-1610.
[http://dx.doi.org/10.1016/j.jiph.2020.07.011] [PMID: 32778421]
[7]
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]
[8]
Gorbalenya, A.E.; Baker, S.C.; Baric, R.S.; De Groot, R.J.; Drosten, C.; Gulyaeva, A.A.; Haagmans, B.L.; Lauber, C.; Leontovich, A.M. Severe acute respiratory syndrome-related coronavirus: the species and its viruses – a statement of the coronavirus study group. Biorxiv, 2020, 5(4), 536-544.
[http://dx.doi.org/10.1101/2020.02.07.937862]
[9]
Petrosillo, N.; Viceconte, G.; Ergonul, O.; Ippolito, G.; Petersen, E. COVID-19, SARS and MERS: Are they closely related? Clin. Microbiol. Infect., 2020, 26(6), 729-734.
[http://dx.doi.org/10.1016/j.cmi.2020.03.026] [PMID: 32234451]
[10]
China CDC Weekly, C. The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China. China CDC Weekly, 2020, 2(8), 113-122.
[http://dx.doi.org/10.46234/ccdcw2020.032] [PMID: 34594836]
[11]
Malinis, M.; McManus, D.; Davis, M.; Topal, J. An overview on the use of antivirals for the treatment of patients with COVID-19 disease. Expert Opin. Investig. Drugs, 2021, 30(1), 45-59.
[http://dx.doi.org/10.1080/13543784.2021.1847270] [PMID: 33151781]
[12]
Ghosh, A.K.; Brindisi, M.; Shahabi, D.; Chapman, M.E.; Mesecar, A.D. Drug development and medicinal chemistry efforts toward SARS-coronavirus and covid-19 therapeutics. ChemMedChem, 2020, 15(11), 907-932.
[http://dx.doi.org/10.1002/cmdc.202000223] [PMID: 32324951]
[13]
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.
[http://dx.doi.org/10.1016/j.cell.2020.02.052] [PMID: 32142651]
[14]
Liu, Z.; Xiao, X.; Wei, X.; Li, J.; Yang, J.; Tan, H.; Zhu, J.; Zhang, Q.; Wu, J.; Liu, L. Composition and divergence of coronavirus spike proteins and host ACE2 receptors predict potential intermediate hosts of SARS‐CoV‐2. J. Med. Virol., 2020, 92(6), 595-601.
[http://dx.doi.org/10.1002/jmv.25726] [PMID: 32100877]
[15]
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, 181(2), 281-292.e6.
[http://dx.doi.org/10.1016/j.cell.2020.02.058] [PMID: 32155444]
[16]
Guo, Y.R.; Cao, Q.D.; Hong, Z.S.; Tan, Y.Y.; Chen, D.; Jin, H.J.; Tan, K.S.; Wang, D.Y.; Yan, Y. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak – an update on the status. Eur. Heart J., 2020, 41(22), 2124-2125.
[http://dx.doi.org/10.1093/eurheartj/ehaa396] [PMID: 32363406]
[17]
Zhang, N.; Jiang, S.; Du, L. Current advancements and potential strategies in the development of MERS-CoV vaccines. Expert Rev. Vaccines, 2014, 13(6), 761-774.
[http://dx.doi.org/10.1586/14760584.2014.912134] [PMID: 24766432]
[18]
Yu, F.; Du, L.; Ojcius, D.M.; Pan, C.; Jiang, S. Measures for diagnosing and treating infections by a novel coronavirus responsible for a pneumonia outbreak originating in Wuhan, China. Microbes Infect., 2020, 22(2), 74-79.
[http://dx.doi.org/10.1016/j.micinf.2020.01.003] [PMID: 32017984]
[19]
Xia, S.; Zhu, Y.; Liu, M.; Lan, Q.; Xu, W.; Wu, Y.; Ying, T.; Liu, S.; Shi, Z.; Jiang, S.; Lu, L. Fusion mechanism of 2019-nCoV and fusion inhibitors targeting HR1 domain in spike protein. Cell. Mol. Immunol., 2020, 17(7), 765-767.
[http://dx.doi.org/10.1038/s41423-020-0374-2] [PMID: 32047258]
[20]
Blaising, J.; Polyak, S.J.; Pécheur, E.I. Arbidol as a broad-spectrum antiviral: An update. Antiviral Res., 2014, 107(1), 84-94.
[http://dx.doi.org/10.1016/j.antiviral.2014.04.006] [PMID: 24769245]
[21]
Boriskin, Y.; Leneva, I.; Pécheur, E.I.; Polyak, S. Arbidol: A broad-spectrum antiviral compound that blocks viral fusion. Curr. Med. Chem., 2008, 15(10), 997-1005.
[http://dx.doi.org/10.2174/092986708784049658] [PMID: 18393857]
[22]
Brooks, M.J.; Sasadeusz, J.J.; Tannock, G.A. Antiviral chemotherapeutic agents against respiratory viruses. Curr. Opin. Pulm. Med., 2004, 10(3), 197-203.
[http://dx.doi.org/10.1097/00063198-200405000-00009] [PMID: 15071371]
[23]
Beigel, J.H.; Nam, H.H.; Adams, P.L.; Krafft, A.; Ince, W.L.; El-Kamary, S.S.; Sims, A.C. Advances in respiratory virus therapeutics – A meeting report from the 6th isirv Antiviral Group conference. Antiviral Res., 2019, 167, 45-67.
[http://dx.doi.org/10.1016/j.antiviral.2019.04.006] [PMID: 30974127]
[24]
Srinivas, P.; Sacha, G.L.; Koval, C. Antivirals for COVID-19. Cleve. Clin. J. Med., 2020, 1-5.
[http://dx.doi.org/10.3949/ccjm.87a.ccc030] [PMID: 32409433]
[25]
Zhang, L.; Liu, Y. Potential interventions for novel coronavirus in China: A systematic review. J. Med. Virol., 2020, 92(5), 479-490.
[http://dx.doi.org/10.1002/jmv.25707] [PMID: 32052466]
[26]
Trofimov, F.A.; Tsyshkova, N.G.; Zotova, S.A.; Grinev, A.N. Synthesis of a new antiviral agent, arbidole. Pharm. Chem. J., 1993, 27(1), 75-76.
[http://dx.doi.org/10.1007/BF00772858]
[27]
Sanders, J.M.; Monogue, M.L.; Jodlowski, T.Z.; Cutrell, J.B. Pharmacologic treatments for coronavirus disease 2019 (COVID-19): A review. JAMA, 2020, 323(18), 1824-1836.
[http://dx.doi.org/10.1001/jama.2020.6019] [PMID: 32282022]
[28]
Villalaín, J. Membranotropic effects of arbidol, a broad anti-viral molecule, on phospholipid model membranes. J. Phys. Chem. B, 2010, 114(25), 8544-8554.
[http://dx.doi.org/10.1021/jp102619w] [PMID: 20527735]
[29]
Mayence, A.; Vanden, E.J.; Baricitinib, A. 2018 novel FDA-approved small molecule inhibiting Janus kinases. Pharmaceuticals, 2019, 12(1), 37.
[http://dx.doi.org/10.3390/ph12010037] [PMID: 30871014]
[30]
Eli Lilly and Company. FDA approves OLUMIANT® (Baricitinib) 2-mg tablets for the treatment of adults with moderately-to-severely active rheumatoid arthritis. PRNewswire; , 2018. Available from: https://investor.lilly.com/node/38996/pdf
[31]
Richardson, P.; Griffin, I.; Tucker, C.; Smith, D.; Oechsle, O.; Phelan, A.; Rawling, M.; Savory, E.; Stebbing, J. Baricitinib as potential treatment for 2019-nCoV acute respiratory disease. Lancet, 2020, 395(10223), e30-e31.
[http://dx.doi.org/10.1016/S0140-6736(20)30304-4] [PMID: 32032529]
[32]
Kalil, A.C.; Patterson, T.F.; Mehta, A.K.; Tomashek, K.M.; Wolfe, C.R.; Ghazaryan, V.; Marconi, V.C.; Ruiz-Palacios, G.M.; Hsieh, L.; Kline, S.; Tapson, V.; Iovine, N.M.; Jain, M.K.; Sweeney, D.A.; El Sahly, H.M.; Branche, A.R.; Regalado Pineda, J.; Lye, D.C.; Sandkovsky, U.; Luetkemeyer, A.F.; Cohen, S.H.; Finberg, R.W.; Jackson, P.E.H.; Taiwo, B.; Paules, C.I.; Arguinchona, H.; Erdmann, N.; Ahuja, N.; Frank, M.; Oh, M.; Kim, E.S.; Tan, S.Y.; Mularski, R.A.; Nielsen, H.; Ponce, P.O.; Taylor, B.S.; Larson, L.; Rouphael, N.G.; Saklawi, Y.; Cantos, V.D.; Ko, E.R.; Engemann, J.J.; Amin, A.N.; Watanabe, M.; Billings, J.; Elie, M.C.; Davey, R.T.; Burgess, T.H.; Ferreira, J.; Green, M.; Makowski, M.; Cardoso, A.; de Bono, S.; Bonnett, T.; Proschan, M.; Deye, G.A.; Dempsey, W.; Nayak, S.U.; Dodd, L.E.; Beigel, J.H. Baricitinib plus remdesivir for hospitalized adults with COVID-19. N. Engl. J. Med., 2021, 384(9), 795-807.
[http://dx.doi.org/10.1056/NEJMoa2031994] [PMID: 33306283]
[33]
Eli Lilly and Company. Baricitinib receives emergency use authorization from the FDA for the treatment of hospitalized patients with COVID-19. PRNewswire; , 2020. Available from: https://investor.lilly.com/node/44041/pdf
[34]
Cantini, F.; Niccoli, L.; Nannini, C.; Matarrese, D.; Di Natale, M.E.; Lotti, P.; Aquilini, D.; Landini, G.; Cimolato, B.; Di Pietro, M.A.; Trezzi, M.; Stobbione, P.; Frausini, G.; Navarra, A.; Nicastri, E.; Sotgiu, G.; Goletti, D. Retrospective, multicentre study on the impact of baricitinib in COVID-19 moderate pneumonia. J. Infect., 2020, 81(4), 647-679.
[http://dx.doi.org/10.1016/j.jinf.2020.06.052] [PMID: 32592703]
[35]
Cantini, F.; Niccoli, L.; Matarrese, D.; Nicastri, E.; Stobbione, P.; Goletti, D. Baricitinib therapy in COVID-19: A pilot study on safety and clinical impact. J. Infect., 2020, 81(2), 318-356.
[http://dx.doi.org/10.1016/j.jinf.2020.04.017] [PMID: 32333918]
[36]
Rodgers, J.; Shepard, S.; Maduskuie, T.; Wang, H.; Falahatpisheh, N.; Rafalski, M.; Arvanitis, A.; Storace, L.; Jalluri, R.; Fridman, J. Heteroarylsubstituted pyrrolo[2,3-b] pyridines and pyrrolo[2,3-b] pyrimidines as Janus kinase inhibitors. U.S. Patent 2007/0135461, 2007.
[37]
Xu, J.; Cai, J.; Chen, J.; Zong, X.; Wu, X.; Ji, M.; Wang, P. An efficient synthesis of baricitinib. J. Chem. Res., 2016, 40(4), 205-208.
[http://dx.doi.org/10.3184/174751916X14569294811333]
[38]
Uno, Y. Camostat mesilate therapy for COVID-19. Intern. Emerg. Med., 2020, 15(8), 1577-1578.
[http://dx.doi.org/10.1007/s11739-020-02345-9] [PMID: 32347443]
[39]
[40]
Breining, P.; Frølund, A.L.; Højen, J.F.; Gunst, J.D.; Staerke, N.B.; Saedder, E.; Cases-Thomas, M.; Little, P.; Nielsen, L.P.; Søgaard, O.S.; Kjolby, M. Camostat mesylate against SARS‐CoV‐2 and COVID‐19—Rationale, dosing and safety. Basic Clin. Pharmacol. Toxicol., 2021, 128(2), 204-212.
[http://dx.doi.org/10.1111/bcpt.13533] [PMID: 33176395]
[41]
The impact of camostat mesilate on COVID-19 infection. Clinicaltrials. gov. Patent NCT04321096, 2020. Available from: https://clinicaltrials.gov/ct2/show/NCT04321096
[42]
De Savi, C.; Hughes, D.L.; Kvaerno, L. Quest for a COVID-19 cure by repurposing small-molecule drugs: mechanism of action, clinical development, synthesis at scale, and outlook for supply. Org. Process Res. Dev., 2020, 24(6), 940-976.
[http://dx.doi.org/10.1021/acs.oprd.0c00233]
[43]
Hoffmann, M.; Hofmann-Winkler, H.; Smith, J.C.; Krüger, N.; Arora, P.; Sørensen, L.K.; Søgaard, O.S.; Hasselstrøm, J.B.; Winkler, M.; Hempel, T.; Raich, L.; Olsson, S.; Danov, O.; Jonigk, D.; Yamazoe, T.; Yamatsuta, K.; Mizuno, H.; Ludwig, S.; Noé, F.; Kjolby, M.; Braun, A.; Sheltzer, J.M.; Pöhlmann, S. Camostat mesylate inhibits SARS-CoV-2 activation by TMPRSS2-related proteases and its metabolite GBPA exerts antiviral activity. EBioMedicine, 2021, 65, 103255.
[http://dx.doi.org/10.1016/j.ebiom.2021.103255] [PMID: 33676899]
[44]
Chen, X.; Xu, Z.; Zeng, S.; Wang, X.; Liu, W.; Qian, L.; Wei, J.; Yang, X.; Shen, Q.; Gong, Z.; Yan, Y. The molecular aspect of antitumor effects of protease inhibitor nafamostat mesylate and its role in potential clinical applications. Front. Oncol., 2019, 9(9), 852.
[http://dx.doi.org/10.3389/fonc.2019.00852] [PMID: 31552177]
[45]
Fujii, S.; Hitomi, Y. New synthetic inhibitors of C1r, C1 esterase thrombin, plasmin, kallikrein and trypsin. Biochimica et Biophysica Acta (BBA) - Enzymology, 1981, 661(2), 342-345.
[http://dx.doi.org/10.1016/0005-2744(81)90023-1] [PMID: 6271224]
[46]
Hoffmann, M.; Schroeder, S.; Kleine-Weber, H.; Müller, M.A.; Drosten, C.; Pöhlmann, S. Nafamostatmesylate 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]
[47]
Aoyama, T.; Ino, Y.; Ozeki, M.; Oda, M.; Sato, T.; Koshiyama, Y.; Suzuki, S.; Fujita, M. Pharmacological studies of FUT-175, nafamstat mesilate. I. Inhibition of protease activity in in vitro and in vivo experiments. Jpn. J. Pharmacol., 1984, 35(3), 203-227.
[http://dx.doi.org/10.1254/jjp.35.203] [PMID: 6482087]
[48]
Asakura, H.; Ogawa, H. Potential of heparin and nafamostat combination therapy for COVID‐19. J. Thromb. Haemost., 2020, 18(6), 1521-1522.
[http://dx.doi.org/10.1111/jth.14858] [PMID: 32302456]
[49]
Clinical Efficacy of Nafamostat Mesylate for COVID-19 Pneumonia. Gyeongsang National University Hospital. Patent NCT04418128, 2020. Available from: https://clinicaltrials.gov/ct2/show/NCT04418128
[50]
Okajima, K.; Uchiba, M.; Murakami, K. Nafamostat mesilate. Cardiovasc. Drug Rev., 1995, 13(1), 51-65.
[http://dx.doi.org/10.1111/j.1527-3466.1995.tb00213.x]
[51]
Kim, H.S.; Lee, K.E.; Oh, J.H.; Jung, C.S.; Choi, D.; Kim, Y.; Jeon, J.S.; Han, D.C.; Noh, H. Cardiac arrest caused by nafamostat mesilate. Kidney Res. Clin. Pract., 2016, 35(3), 187-189.
[http://dx.doi.org/10.1016/j.krcp.2015.10.003] [PMID: 27668164]
[52]
Kang, M.W.; Song, H.J.; Kang, S.K.; Kim, Y.; Jung, S.; Jee, S.; Moon, J.Y.; Suh, K.; Lee, S.D.; Jeon, B.H.; Kim, C.S. Nafamostat mesylate inhibits TNF-α-induced vascular endothelial cell dysfunction by inhibiting reactive oxygen species production. Korean J. Physiol. Pharmacol., 2015, 19(3), 229-234.
[http://dx.doi.org/10.4196/kjpp.2015.19.3.229] [PMID: 25954127]
[53]
Sham, H.L.; Kempf, D.J.; Molla, A.; Marsh, K.C.; Kumar, G.N.; Chen, C.M.; Kati, W.; Stewart, K.; Lal, R.; Hsu, A.; Betebenner, D.; Korneyeva, M.; Vasavanonda, S.; McDonald, E.; Saldivar, A.; Wideburg, N.; Chen, X.; Niu, P.; Park, C.; Jayanti, V.; Grabowski, B.; Granneman, G.R.; Sun, E.; Japour, A.J.; Leonard, J.M.; Plattner, J.J.; Norbeck, D.W. ABT-378, a highly potent inhibitor of the human immunodeficiency virus protease. Antimicrob. Agents Chemother., 1998, 42(12), 3218-3224.
[http://dx.doi.org/10.1128/AAC.42.12.3218] [PMID: 9835517]
[54]
Abbott Laboratoriues. NDA21-226 NDA21-251; , 2000. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21-226_Kaletra.cfm
[55]
Frediansyah, A.; Tiwari, R.; Sharun, K.; Dhama, K.; Harapan, H. Antivirals for COVID-19: A critical review. Clin. Epidemiol. Glob. Health, 2021, 9, 90-98.
[http://dx.doi.org/10.1016/j.cegh.2020.07.006] [PMID: 33521390]
[56]
Chandwani, A.; Shuter, J. Lopinavir/ritonavir in the treatment of HIV-1 infection: a review. Ther. Clin. Risk Manag., 2008, 4(5), 1023-1033.
[PMID: 19209283]
[57]
Mangum, E.M.; Graham, K.K. Lopinavir-ritonavir: A new protease inhibitor. Pharmacotherapy, 2001, 21(11), 1352-1363.
[http://dx.doi.org/10.1592/phco.21.17.1352.34419] [PMID: 11714208]
[58]
Hussain, N.; Yoganathan, A.; Hewage, S.; Alom, S.; Harky, A. The effect of antivirals on COVID-19: A systematic review. Expert Rev. Anti Infect. Ther., 2021, 19(4), 473-486.
[http://dx.doi.org/10.1080/14787210.2021.1823832] [PMID: 32924650]
[59]
Ghosh, A.K.; Bilcer, G.; Schiltz, G. Syntheses of FDA approved HIV protease inhibitors. Synthesis, 2001, 2001(15), 2203-2229.
[http://dx.doi.org/10.1055/s-2001-18434] [PMID: 30393404]
[60]
Stoner, E.J.; Cooper, A.J.; Dickman, D.A.; Kolaczkowski, L.; Lallaman, J.E.; Liu, J.H.; Oliver-Shaffer, P.A.; Patel, K.M.; Paterson, J.B.; Plata, D.J.; Riley, D.A.; Sham, H.L.; Stengel, P.J.; Tien, J.H.J. Synthesis of HIV protease inhibitor ABT-378 (Lopinavir). Org. Process Res. Dev., 2000, 4(4), 264-269.
[http://dx.doi.org/10.1021/op990202j]
[61]
Stoner, E.J.; Stengel, P.J.; Cooper, A.J. Synthesis of ABT-378, an HIV protease inhibitor candidate: avoiding the use of carbodiimides in a difficult peptide coupling. Org. Process Res. Dev., 1999, 3(2), 145-148.
[http://dx.doi.org/10.1021/op980214p]
[62]
Ahmad, B.; Batool, M.; Ain, Q.; Kim, M.S.; Choi, S. Exploring the binding mechanism of PF-07321332 SARS-CoV-2 protease inhibitor through molecular dynamics and binding free energy simulations. Int. J. Mol. Sci., 2021, 22(17), 9124.
[http://dx.doi.org/10.3390/ijms22179124] [PMID: 34502033]
[63]
Owen, D.R.; Allerton, C.M.N.; Anderson, A.S.; Aschenbrenner, L.; Avery, M.; Berritt, S.; Boras, B.; Cardin, R.D.; Carlo, A.; Coffman, K.J.; Dantonio, A.; Di, L.; Eng, H.; Ferre, R.; Gajiwala, K.S.; Gibson, S.A.; Greasley, S.E.; Hurst, B.L.; Kadar, E.P.; Kalgutkar, A.S.; Lee, J.C.; Lee, J.; Liu, W.; Mason, S.W.; Noell, S.; Novak, J.J.; Obach, R.S.; Ogilvie, K.; Patel, N.C.; Pettersson, M.; Rai, D.K.; Reese, M.R.; Sammons, M.F.; Sathish, J.G.; Singh, R.S.P.; Steppan, C.M.; Stewart, A.E.; Tuttle, J.B.; Updyke, L.; Verhoest, P.R.; Wei, L.; Yang, Q.; Zhu, Y. An oral SARS-CoV-2 M pro inhibitor clinical candidate for the treatment of COVID-19. Science, 2021, 374(6575), 1586-1593.
[http://dx.doi.org/10.1126/science.abl4784] [PMID: 34726479]
[64]
Emergency Use Authorization 105. Pfizer Inc., 2021. Available from: https://www.fda.gov/media/155049/download
[65]
FDA news release. Coronavirus (COVID-19) update: FDA authorizes first oral antiviral for treatment of COVID-19. 2021. Available from: https://doi.org/https://www.fda.gov/news-events/pressannouncements/coronavirus-covid-19-update-fda-authorizes-firstoral-antiviral-treatment-covid-19
[66]
Ghosh, A.K.; Dawson, Z.L.; Mitsuya, H. Darunavir, a conceptually new HIV-1 protease inhibitor for the treatment of drug-resistant HIV. Bioorg. Med. Chem., 2007, 15(24), 7576-7580.
[http://dx.doi.org/10.1016/j.bmc.2007.09.010] [PMID: 17900913]
[67]
Prezista FDA Approval History. Drugs.com; , 2006. Available from: https://www.drugs.com/history/prezista.html
[68]
Riva, A.; Conti, F.; Bernacchia, D.; Pezzati, L.; Sollima, S.; Merli, S.; Siano, M.; Lupo, A.; Rusconi, S.; Cattaneo, D.; Gervasoni, C. Darunavir does not prevent SARS-CoV-2 infection in HIV patients. Pharmacol. Res., 2020, 157, 104826.
[http://dx.doi.org/10.1016/j.phrs.2020.104826] [PMID: 32325127]
[69]
Fintelman-Rodrigues, N.; Sacramento, C.Q.; Ribeiro Lima, C.; Souza da Silva, F.; Ferreira, A.C.; Mattos, M.; de Freitas, C.S.; Cardoso, S.V.; da Silva, G.D.S.; Temerozo, J.R.; Miranda, M.D.; Matos, A.R.; Bozza, F.A.; Carels, N.; Alves, C.R.; Siqueira, M.M.; Bozza, P.T.; Souza, T.M.L. Atazanavir, alone or in combination with ritonavir, inhibits SARS-CoV-2 replication and proinflammatory cytokine production. Antimicrob. Agents Chemother., 2020, 64(10), e00825-20.
[http://dx.doi.org/10.1128/AAC.00825-20] [PMID: 32759267]
[70]
Davis, D.A.; Soule, E.E.; Davidoff, K.S.; Daniels, S.I.; Naiman, N.E.; Yarchoan, R. Activity of human immunodeficiency virus type 1 protease inhibitors against the initial autocleavage in Gag-Pol polyprotein processing. Antimicrob. Agents Chemother., 2012, 56(7), 3620-3628.
[http://dx.doi.org/10.1128/AAC.00055-12] [PMID: 22508308]
[71]
Eastman, R.T.; Roth, J.S.; Brimacombe, K.R.; Simeonov, A.; Shen, M.; Patnaik, S.; Hall, M.D. Remdesivir: A review of its discovery and development leading to emergency use authorization for treatment of COVID-19. ACS Cent. Sci., 2020, 6(5), 672-683.
[http://dx.doi.org/10.1021/acscentsci.0c00489] [PMID: 32483554]
[72]
[73]
Brown, A.J.; Won, J.J.; Graham, R.L.; Dinnon, K.H., III; Sims, A.C.; Feng, J.Y.; Cihlar, T.; Denison, M.R.; Baric, R.S.; Sheahan, T.P. Broad spectrum antiviral remdesivir inhibits human endemic and zoonotic deltacoronaviruses with a highly divergent RNA dependent RNA polymerase. Antiviral Res., 2019, 169(6), 104541.
[http://dx.doi.org/10.1016/j.antiviral.2019.104541] [PMID: 31233808]
[74]
Al-Tawfiq, J.A.; Al-Homoud, A.H.; Memish, Z.A. Remdesivir as a possible therapeutic option for the COVID-19. Travel Med. Infect. Dis., 2020, 34, 101615.
[http://dx.doi.org/10.1016/j.tmaid.2020.101615] [PMID: 32145386]
[75]
Agostini, M.L.; Andres, E.L.; Sims, A.C.; Graham, R.L.; Sheahan, T.P.; Lu, X.; Smith, E.C.; Case, J.B.; Feng, J.Y.; Jordan, R.; Ray, A.S.; Cihlar, T.; Siegel, D.; Mackman, R.L.; Clarke, M.O.; Baric, R.S.; Denison, M.R. Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease. MBio, 2018, 9(2), e00221-18.
[http://dx.doi.org/10.1128/mBio.00221-18] [PMID: 29511076]
[76]
Al Bujuq, N. Methods of synthesis of remdesivir, favipiravir, hydroxychloroquine, and chloroquine: four small molecules repurposed for clinical trials during the covid-19 pandemic. Synthesis, 2020, 52(24), 3735-3750.
[http://dx.doi.org/10.1055/s-0040-1707386]
[77]
Zarenezhad, E.; Behrouz, S.; Farjam, M.; Rad, M.N.S. A mini review on discovery and synthesis of remdesivir as an effective and promising drug against COVID-19. Russ. J. Bioorganic Chem., 2021, 47(3), 609-621.
[http://dx.doi.org/10.1134/S1068162021030183] [PMID: 34149273]
[78]
Siegel, D.; Hui, H.C.; Doerffler, E.; Clarke, M.O.; Chun, K.; Zhang, L.; Neville, S.; Carra, E.; Lew, W.; Ross, B.; Wang, Q.; Wolfe, L.; Jordan, R.; Soloveva, V.; Knox, J.; Perry, J.; Perron, M.; Stray, K.M.; Barauskas, O.; Feng, J.Y.; Xu, Y.; Lee, G.; Rheingold, A.L.; Ray, A.S.; Bannister, R.; Strickley, R.; Swaminathan, S.; Lee, W.A.; Bavari, S.; Cihlar, T.; Lo, M.K.; Warren, T.K.; Mackman, R.L. Discovery and synthesis of a phosphoramidate prodrug of a pyrrolo[2,1-f][triazin-4-amino] adenine c-nucleoside (GS-5734) for the treatment of ebola and emerging viruses. J. Med. Chem., 2017, 60(5), 1648-1661.
[http://dx.doi.org/10.1021/acs.jmedchem.6b01594] [PMID: 28124907]
[79]
Khanal, P. Remdesivir for COVID-19 treatment: Mechanism of action, synthesis, and clinical trials. World J. Pharm. Pharm. Sci., 2020, 9, 1062-1068.
[http://dx.doi.org/10.20959/wjpps20208-16808]
[80]
Ko, W.C.; Rolain, J.M.; Lee, N.Y.; Chen, P.L.; Huang, C.T.; Lee, P.I.; Hsueh, P.R. Arguments in favour of remdesivir for treating SARS-CoV-2 infections. Int. J. Antimicrob. Agents, 2020, 55(4), 105933.
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105933] [PMID: 32147516]
[81]
Jayk Bernal, A.; Gomes da Silva, M.M.; Musungaie, D.B.; Kovalchuk, E.; Gonzalez, A.; Delos Reyes, V.; Martín-Quirós, A.; Caraco, Y.; Williams-Diaz, A.; Brown, M.L.; Du, J.; Pedley, A.; Assaid, C.; Strizki, J.; Grobler, J.A.; Shamsuddin, H.H.; Tipping, R.; Wan, H.; Paschke, A.; Butterton, J.R.; Johnson, M.G.; De Anda, C. Molnupiravirfor oral treatment of COVID-19 in non-hospitalized patients. N. Engl. J. Med., 2022, 386(6), 509-520.
[http://dx.doi.org/10.1056/NEJMoa2116044] [PMID: 34914868]
[82]
FDA news release. Coronavirus (COVID-19) Update: FDA Authorizes Additional Monoclonal Antibody for Treatment of COVID-19. 2021. Available from: https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-additional-oral-antiviral-treatment-covid-19-certain
[83]
Ahlqvist, G.P.; McGeough, C.P.; Senanayake, C.; Armstrong, J.D.; Yadaw, A.; Roy, S.; Ahmad, S.; Snead, D.R.; Jamison, T.F. Progress toward a large-scale synthesis of molnupiravir(MK-4482, EIDD-2801) from cytidine. ACS Omega, 2021, 6(15), 10396-10402.
[http://dx.doi.org/10.1021/acsomega.1c00772] [PMID: 34056192]
[84]
Hampton, T. New flu antiviral candidate may thwart drug resistance. JAMA-. JAMA, 2020, 323(1), 17.
[http://dx.doi.org/10.1001/jama.2019.20225] [PMID: 31910262]
[85]
Shiraki, K.; Daikoku, T. Favipiravir, an anti-influenza drug against life-threatening RNA virus infections. Pharmacol. Ther., 2020, 209, 107512.
[http://dx.doi.org/10.1016/j.pharmthera.2020.107512] [PMID: 32097670]
[86]
Taisho Toyama Pharmaceutical Co. L. Avigan® (Favipiravir) Tablets Prescribing Information; , 2017. Available from: https://www.cdc.gov.tw/File/Get/ht8jUiB_MI-
[87]
Rizzardini, G. Covid-19 clinical study to evaluate the performance and safety of favipiravir in covid-19. Clinicaltrials.gov; , 2020. Available from: https://clinicaltrials.gov/ct2/show/NCT04336904?cond=COVID-19&draw=3&rank=14
[88]
Russia approves first covid-19 prescription drug for sale in pharmacies. Reuters Staf., 2020. Available from: https://www.reuters. com/article/us-health-coronavirus-russia-rpharm-idUSKBN26917Z
[89]
Ueda, M.; Tanimoto, T.; Murayama, A.; Ozaki, A.; Kami, M. Japan’s drug regulation during the COVID-19 pandemic: lessons from a case study of favipiravir. Clin. Pharmacol. Ther., 2022, 111(3), 545-547.
[http://dx.doi.org/10.1002/cpt.2251] [PMID: 33882157]
[90]
Pulla, P. Is favipiravir good for COVID-19? clinical trial says no, press release says yes. Science.thewire.in., 2020. Available from: https://science.thewire.in/the-sciences/favipiravir-glenmark-open-label-trial-primary-endpoints-efficacy-cure-times-misleading-press-release/
[91]
Furuta, Y.; Egawa, H. Nitrogenous heterocyclic carboxamide derivatives or salts thereof and antiviral agents containing both. Patent WO2000010569, 2000. Available from: https://patentscope. wipo.int/search/en/detail.jsf?docId=WO2000010569
[92]
Liu, F.L.; Li, C.Q.; Xiang, H.Y.; Feng, S. A practical and step-economic route to Favipiravir. Chem. Pap., 2017, 71(11), 2153-2158.
[http://dx.doi.org/10.1007/s11696-017-0208-6]
[93]
Guo, Q.; Xu, M.; Guo, S.; Zhu, F.; Xie, Y.; Shen, J. The complete synthesis of favipiravir from 2-aminopyrazine. Chem. Pap., 2019, 73(5), 1043-1051.
[http://dx.doi.org/10.1007/s11696-018-0654-9]
[94]
Furuta, Y.; Komeno, T.; Nakamura, T. Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase. Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci., 2017, 93(7), 449-463.
[http://dx.doi.org/10.2183/pjab.93.027] [PMID: 28769016]
[95]
Lau, J. The story of ribavirin. Hepcassoc, 2002, 35(5) Available from: http://www.hepcassoc.org/news/article39.html
[96]
Sidwell, R. W.; Huffman, J. H.; Khare, G. P.; Allen, L. B.; Witkowski, J. T.; Robins, R. K. Broad-spectrum antiviral activity of virazole: 1-beta-d-ribofuranosyl-1,2,4-triazole-3-carboxamide. Science, 1972, 177, 705-706.
[http://dx.doi.org/10.1126/science.177.4050.705]
[97]
Ribasphere FDA Approval History. Drugs.com; , 2004. Available from: https://www.drugs.com/history/ribasphere.html
[98]
Chen, F.; Chan, K.H.; Jiang, Y.; Kao, R.Y.T.; Lu, H.T.; Fan, K.W.; Cheng, V.C.C.; Tsui, W.H.W.; Hung, I.F.N.; Lee, T.S.W.; Guan, Y.; Peiris, J.S.M.; Yuen, K.Y. In vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds. J. Clin. Virol., 2004, 31(1), 69-75.
[http://dx.doi.org/10.1016/j.jcv.2004.03.003] [PMID: 15288617]
[99]
Morgenstern, B.; Michaelis, M.; Baer, P.C.; Doerr, H.W.; Cinatl, J. Jr Ribavirin and interferon-β synergistically inhibit SARS-associated coronavirus replication in animal and human cell lines. Biochem. Biophys. Res. Commun., 2005, 326(4), 905-908.
[http://dx.doi.org/10.1016/j.bbrc.2004.11.128] [PMID: 15607755]
[100]
Falzarano, D.; de Wit, E.; Rasmussen, A.L.; Feldmann, F.; Okumura, A.; Scott, D.P.; Brining, D.; Bushmaker, T.; Martellaro, C.; Baseler, L.; Benecke, A.G.; Katze, M.G.; Munster, V.J.; Feldmann, H. Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV–infected rhesus macaques. Nat. Med., 2013, 19(10), 1313-1317.
[http://dx.doi.org/10.1038/nm.3362] [PMID: 24013700]
[101]
Li, H.; Xiong, N.; Li, C.; Gong, Y.; Liu, L.; Yang, H.; Tan, X.; Jiang, N.; Zong, Q.; Wang, J.; Lu, Z.; Yin, X. Efficacy of ribavirin and interferon-α therapy for hospitalized patients with COVID-19: A multicenter, retrospective cohort study. Int. J. Infect. Dis., 2021, 104, 641-648.
[http://dx.doi.org/10.1016/j.ijid.2021.01.055] [PMID: 33515771]
[102]
Tong, S.; Su, Y.; Yu, Y.; Wu, C.; Chen, J.; Wang, S.; Jiang, J. Ribavirin therapy for severe COVID-19: A retrospective cohort study. Int. J. Antimicrob. Agents, 2020, 56(3), 106114.
[http://dx.doi.org/10.1016/j.ijantimicag.2020.106114] [PMID: 32712334]
[103]
Witkowski, J.T.; Robins, R.K.; Sidwell, R.W.; Simon, L.N. Design, synthesis, and broad spectrum antiviral activity of 1-.beta.-D-ribofuranosyl-1,2,4-triazole-3-carboxamide and related nucleosides. J. Med. Chem., 1972, 15(11), 1150-1154.
[http://dx.doi.org/10.1021/jm00281a014] [PMID: 4347550]
[104]
Maag, D.; Castro, C.; Hong, Z.; Cameron, C.E. Hepatitis C virus RNA-dependent RNA polymerase (NS5B) as a mediator of the antiviral activity of ribavirin. J. Biol. Chem., 2001, 276(49), 46094-46098.
[http://dx.doi.org/10.1074/jbc.C100349200] [PMID: 11602568]
[105]
Crotty, S.; Cameron, C.E.; Andino, R. RNA virus error catastrophe: Direct molecular test by using ribavirin. Proc. Natl. Acad. Sci., 2001, 98(12), 6895-6900.
[http://dx.doi.org/10.1073/pnas.111085598] [PMID: 11371613]
[106]
Zhou, S.; Liu, R.; Baroudy, B.M.; Malcolm, B.A.; Reyes, G.R. The effect of ribavirin and IMPDH inhibitors on hepatitis C virus subgenomic replicon RNA. Virology, 2003, 310(2), 333-342.
[http://dx.doi.org/10.1016/S0042-6822(03)00152-1] [PMID: 12781720]
[107]
Nojomi, M.; Yassin, Z.; Keyvani, H.; Makiani, M.J.; Roham, M.; Laali, A.; Dehghan, N.; Navaei, M.; Ranjbar, M. Effect of Arbidol (Umifenovir) on COVID-19: A randomized controlled trial. BMC Infect. Dis., 2020, 20(1), 954.
[http://dx.doi.org/10.1186/s12879-020-05698-w] [PMID: 33317461]
[108]
Liu, D.; Zeng, X.; Ding, Z.; Lv, F.; Mehta, J.L.; Wang, X. Adverse cardiovascular effects of anti-COVID-19 drugs. Front. Pharmacol., 2021, 12, 699949.
[http://dx.doi.org/10.3389/fphar.2021.699949] [PMID: 34512335]
[109]
Zhuravel, S.V.; Khmelnitskiy, O.K.; Burlaka, O.O.; Gritsan, A.I.; Goloshchekin, B.M.; Kim, S.; Hong, K.Y. Nafamostat in hospitalized patients with moderate to severe COVID-19 pneumonia: a randomised Phase II clinical trial. EClinicalMedicine, 2021, 41, 101169.
[http://dx.doi.org/10.1016/j.eclinm.2021.101169] [PMID: 34723164]
[110]
Cao, B.; Wang, Y.; Wen, D.; Liu, W.; Wang, J.; Fan, G.; Ruan, L.; Song, B.; Cai, Y.; Wei, M.; Li, X.; Xia, J.; Chen, N.; Xiang, J.; Yu, T.; Bai, T.; Xie, X.; Zhang, L.; Li, C.; Yuan, Y.; Chen, H.; Li, H.; Huang, H.; Tu, S.; Gong, F.; Liu, Y.; Wei, Y.; Dong, C.; Zhou, F.; Gu, X.; Xu, J.; Liu, Z.; Zhang, Y.; Li, H.; Shang, L.; Wang, K.; Li, K.; Zhou, X.; Dong, X.; Qu, Z.; Lu, S.; Hu, X.; Ruan, S.; Luo, S.; Wu, J.; Peng, L.; Cheng, F.; Pan, L.; Zou, J.; Jia, C.; Wang, J.; Liu, X.; Wang, S.; Wu, X.; Ge, Q.; He, J.; Zhan, H.; Qiu, F.; Guo, L.; Huang, C.; Jaki, T.; Hayden, F.G.; Horby, P.W.; Zhang, D.; Wang, C. A trial of lopinavir–ritonavir in adults hospitalized with severe covid-19. N. Engl. J. Med., 2020, 382(19), 1787-1799.
[http://dx.doi.org/10.1056/NEJMoa2001282] [PMID: 32187464]
[111]
Pfizer shares in vitro efficacy of novel covid-19 oral treatment against omicron variant. 2022. Available from: https://www.pfizer.com/news/press-release/press-release-detail/pfizer-shares-vitro-efficacy-novel-covid-19-oral-treatment
[112]
Aygün, İ.; Kaya, M.; Alhajj, R. Identifying side effects of commonly used drugs in the treatment of Covid 19. Sci. Rep., 2020, 10(1), 21508.
[http://dx.doi.org/10.1038/s41598-020-78697-1] [PMID: 33299085]
[113]
Fan, Q.; Zhang, B.; Ma, J.; Zhang, S. Safety profile of the antiviral drug remdesivir: An update. Biomed. Pharmacother., 2020, 130, 110532.
[http://dx.doi.org/10.1016/j.biopha.2020.110532] [PMID: 32707440]
[114]
Arribas, J.R.; Bhagani, S.; Lobo, S.M.; Khaertynova, I.; Mateu, L.; Fishchuk, R.; Park, W.Y.; Hussein, K.; Kim, S.W.; Ghosn, J.; Brown, M.L.; Zhang, Y.; Gao, W.; Assaid, C.; Grobler, J.A.; Strizki, J.; Vesnesky, M.; Paschke, A.; Butterton, J.R.; De Anda, C. Randomized trial of molnupiravir or placebo in patients hospitalized with covid-19. NEJM Evid, 2021, 1(2), 1-13.
[http://dx.doi.org/10.1056/EVIDoa2100044]
[115]
Kaur, R.J.; Charan, J.; Dutta, S.; Sharma, P.; Bhardwaj, P.; Sharma, P.; Lugova, H.; Krishnapillai, A.; Islam, S.; Haque, M.; Misra, S. Favipiravir use in COVID-19: Analysis of suspected adverse drug events reported in the who database. Infect. Drug Resist., 2020, 13, 4427-4438.
[http://dx.doi.org/10.2147/IDR.S287934] [PMID: 33364790]
[116]
Wang, Y.; Li, W.; Jiang, Z.; Xi, X.; Zhu, Y. Assessment of the efficacy and safety of Ribavirin in treatment of coronavirus-related pneumonia (SARS, MERS and COVID-19). Medicine, 2020, 99(38), e22379.
[http://dx.doi.org/10.1097/MD.0000000000022379] [PMID: 32957417]

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