Clinical Development of Antivirals Against SARS-CoV-2 and Its Variants

Overview

Journal Curr Res Microb Sci

Specialty Microbiology

Date 2023 Dec 27

PMID 38149085

Authors

Qiaoshuai Lan

Yan Yan

Guangxu Zhang

Shuai Xia

Jie Zhou

Lu Lu

Shibo Jiang

Affiliations

Soon will be listed here.

Abstract

The unceasing global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) calls for the development of novel therapeutics. Although many newly developed antivirals and repurposed antivirals have been applied to the treatment of coronavirus disease 2019 (COVID-19), antivirals showing satisfactory clinical efficacy are few in number. In addition, the loss of sensitivity to variants of concern (VOCs) and lack of oral bioavailability have also limited the clinical application of some antivirals. These facts remind us to develop more potent and broad-spectrum antivirals with better pharmacokinetic/pharmacodynamic properties to fight against infections from SARS-CoV-2, its variants, and other human coronaviruses (HCoVs). In this review, we summarize the latest advancements in the clinical development of antivirals against infections by SARS-CoV-2 and its variants.

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References

Cao Z, Gao W, Bao H, Feng H, Mei S, Chen P . VV116 versus Nirmatrelvir-Ritonavir for Oral Treatment of Covid-19. N Engl J Med. 2022; 388(5):406-417. PMC: 9812289. DOI: 10.1056/NEJMoa2208822. View

Naggie S, Boulware D, Lindsell C, Stewart T, Gentile N, Collins S . Effect of Ivermectin vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19: A Randomized Clinical Trial. JAMA. 2022; 328(16):1595-1603. PMC: 9587497. DOI: 10.1001/jama.2022.18590. View

Hammond J, Leister-Tebbe H, Gardner A, Abreu P, Bao W, Wisemandle W . Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19. N Engl J Med. 2022; 386(15):1397-1408. PMC: 8908851. DOI: 10.1056/NEJMoa2118542. View

Lan Q, Xia S, Lu L . Coronavirus Entry Inhibitors. Adv Exp Med Biol. 2022; 1366:101-121. DOI: 10.1007/978-981-16-8702-0_7. View

Good S, Westover J, Jung K, Zhou X, Moussa A, La Colla P . AT-527, a Double Prodrug of a Guanosine Nucleotide Analog, Is a Potent Inhibitor of SARS-CoV-2 and a Promising Oral Antiviral for Treatment of COVID-19. Antimicrob Agents Chemother. 2021; 65(4). PMC: 8097421. DOI: 10.1128/AAC.02479-20. View

Townsend J, Hassler H, Wang Z, Miura S, Singh J, Kumar S . The durability of immunity against reinfection by SARS-CoV-2: a comparative evolutionary study. Lancet Microbe. 2021; 2(12):e666-e675. PMC: 8486316. DOI: 10.1016/S2666-5247(21)00219-6. View

Zhu Y, Yu D, Yan H, Chong H, He Y . Design of Potent Membrane Fusion Inhibitors against SARS-CoV-2, an Emerging Coronavirus with High Fusogenic Activity. J Virol. 2020; 94(14). PMC: 7343218. DOI: 10.1128/JVI.00635-20. View

Pan H, Peto R, Henao-Restrepo A, Preziosi M, Sathiyamoorthy V, Abdool Karim Q . Repurposed Antiviral Drugs for Covid-19 - Interim WHO Solidarity Trial Results. N Engl J Med. 2020; 384(6):497-511. PMC: 7727327. DOI: 10.1056/NEJMoa2023184. View

Hillen H . Structure and function of SARS-CoV-2 polymerase. Curr Opin Virol. 2021; 48:82-90. PMC: 8023233. DOI: 10.1016/j.coviro.2021.03.010. View

10.

Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G . A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020; 382(19):1787-1799. PMC: 7121492. DOI: 10.1056/NEJMoa2001282. View

11.

Udwadia Z, Singh P, Barkate H, Patil S, Rangwala S, Pendse A . Efficacy and safety of favipiravir, an oral RNA-dependent RNA polymerase inhibitor, in mild-to-moderate COVID-19: A randomized, comparative, open-label, multicenter, phase 3 clinical trial. Int J Infect Dis. 2020; 103:62-71. PMC: 7668212. DOI: 10.1016/j.ijid.2020.11.142. View

12.

Razonable R, OHoro J, Hanson S, Arndt R, Speicher L, Seville T . Comparable Outcomes for Bebtelovimab and Ritonavir-Boosted Nirmatrelvir Treatment in High-Risk Patients With Coronavirus Disease-2019 During Severe Acute Respiratory Syndrome Coronavirus 2 BA.2 Omicron Epoch. J Infect Dis. 2022; 226(10):1683-1687. PMC: 9494486. DOI: 10.1093/infdis/jiac346. View

13.

Tolouian R, Mulla Z, Jamaati H, Babamahmoodi A, Marjani M, Eskandari R . Effect of bromhexine in hospitalized patients with COVID-19. J Investig Med. 2021; 71(7):691-699. DOI: 10.1136/jim-2020-001747. View

14.

Reis G, Silva E, Silva D, Thabane L, Milagres A, Ferreira T . Effect of Early Treatment with Ivermectin among Patients with Covid-19. N Engl J Med. 2022; 386(18):1721-1731. PMC: 9006771. DOI: 10.1056/NEJMoa2115869. View

15.

Hung I, Lung K, Tso E, Liu R, Chung T, Chu M . Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. Lancet. 2020; 395(10238):1695-1704. PMC: 7211500. DOI: 10.1016/S0140-6736(20)31042-4. View

16.

Wang G, Yang M, Duan Z, Liu F, Jin L, Long C . Dalbavancin binds ACE2 to block its interaction with SARS-CoV-2 spike protein and is effective in inhibiting SARS-CoV-2 infection in animal models. Cell Res. 2020; 31(1):17-24. PMC: 7705431. DOI: 10.1038/s41422-020-00450-0. View

17.

Xia S, Liu M, Wang C, Xu W, Lan Q, Feng S . 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. PMC: 7104723. DOI: 10.1038/s41422-020-0305-x. View

18.

Li K, Meyerholz D, Bartlett J, McCray Jr P . The TMPRSS2 Inhibitor Nafamostat Reduces SARS-CoV-2 Pulmonary Infection in Mouse Models of COVID-19. mBio. 2021; 12(4):e0097021. PMC: 8406266. DOI: 10.1128/mBio.00970-21. View

19.

Hsu H, Yang C, Lee Y, Lin Y, Chang S, Yang R . Remdesivir and Cyclosporine Synergistically Inhibit the Human Coronaviruses OC43 and SARS-CoV-2. Front Pharmacol. 2021; 12:706901. PMC: 8409573. DOI: 10.3389/fphar.2021.706901. View

20.

Kabinger F, Stiller C, Schmitzova J, Dienemann C, Kokic G, Hillen H . Mechanism of molnupiravir-induced SARS-CoV-2 mutagenesis. Nat Struct Mol Biol. 2021; 28(9):740-746. PMC: 8437801. DOI: 10.1038/s41594-021-00651-0. View