2022 / 06

Next Paper
DOI: 10.24075/brsmu.2022.071

ORIGINAL RESEARCH

Efficacy of favipiravir and molnupiravir against novel SARS-CoV-2 variants in vitro and in vivo

Siniavin AE1,2, Russu LI1, Vasina DV1, Shidlovskaya EV1, Kuznetsova NA1, Gushchin VA1,3, Gintsburg AL1,4
About authors

1 Gamaleya National Research Center for Epidemiology and Microbiology, Moscow, Russia

2 Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia

3 Lomonosov Moscow State University, Moscow, Russia

4 Sechenov University, Moscow, Russia

Correspondence should be addressed: Andrey E. Sinyavin
Gamalei, 16, Moscow, 123098, Russia; ur.xednay@39isyerdna

About paper

Funding: the study was supported by the Russian Ministry of Health, grant № 121111200070-4 (P16).

Acknowledgments: the authors would like to thank the staff of N.I. N.F. Gamaleya A. Zakharova and T. Remizov for organizing the supply of reagents for the study.

Author contribution: Sinyavin AE — design of the experiment, study of antiviral activity, data analysis, writing the text; Russu LI — work with the virus and animals; Vasina DV — work with animals; Shidlovskaya EV, Kuznetsova NA — PCR analysis, data processing; Gushchin VA — research supervision, text editing; Gunzburg AL — approval of the research concept.

Compliance with ethical standards: the study was approved by the ethics committee of the Federal State Budgetary Institution “N.N. N.F. Gamaleya" of the Ministry of Health of the Russian Federation (protocol № 27 of June 6, 2022); conducted in compliance with the principles of the Declaration of Helsinki of the World Medical Association.

Received: 2022-12-05 Accepted: 2022-12-20 Published online: 2022-12-31
|
  1. Yousuke F, Takashi K, Takaaki N. Favipiravir (T-705), a broad-spectrum inhibitor of viral RNA polymerase. Proc Jpn Acad Ser B Phys Biol Sci. 2017; 93 (7): 449–63.
  2. McMahon JH, Lau JS, Coldham A, et al. Favipiravir in early symptomatic COVID-19, a randomised placebo-controlled trial. EClinicalMedicine. 2022; 20 (54): 101703.
  3. Yanagisawa K, Takara K, Suga H, et al. The Assessment of the Efficacy and Safety of Favipiravir for Patients with SARS-CoV-2 Infection: A Multicenter Non-randomized, Uncontrolled Single-arm Prospective Study. Intern Med. 2022; 61 (21): 3197–204.
  4. Bosaeed M, Alharbi A, Mahmoud E, et al. Efficacy of favipiravir in adults with mild COVID-19: a randomized, double-blind, multicentre, placebo-controlled clinical trial. Clin Microbiol Infect. 2022; 28 (4): 602–8.
  5. Lee CC, Hsieh CC, Ko WC. Molnupiravir-A Novel Oral Anti-SARS-CoV-2 Agent. Antibiotics (Basel). 2021; 10 (11): 1294.
  6. Toots M, Yoon JJ, Hart M, Natchus MG, Painter GR, Plemper RK. Quantitative efficacy paradigms of the influenza clinical drug candidate EIDD-2801 in the ferret model. Transl Res. 2020; 218: 16–28.
  7. Yoon JJ, Toots M, Lee S, et al. Orally Efficacious Broad-Spectrum Ribonucleoside Analog Inhibitor of Influenza and Respiratory Syncytial Viruses. Antimicrob Agents Chemother. 2018; 62 (8): e00766–18.
  8. Sheahan TP, Sims AC, Zhou S, at al. An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice. Sci Transl Med. 2020; 12 (541): eabb5883.
  9. Wahl A, Gralinski LE, Johnson CE, et al. SARS-CoV-2 infection is effectively treated and prevented by EIDD-2801. Nature. 2021; 591 (7850): 451–7.
  10. Painter WP, Holman W, Bush JA, Almazedi F, Malik H, Eraut NC, Morin MJ, Szewczyk LJ, Painter GR. Human Safety, Tolerability, and Pharmacokinetics of Molnupiravir, a Novel Broad-Spectrum Oral Antiviral Agent with Activity Against SARS-CoV-2. Antimicrob Agents Chemother. 202; 65 (5): e02428–20.
  11. Imran M, Arora MK, Asdaq SM, et al. Discovery, Development, and Patent Trends on Molnupiravir: A Prospective Oral Treatment for COVID-19. Molecules. 2021; 26 (19): 5795.
  12. Kabinger А, Stiller С, Schmitzová J, Dienemann C, Kokic G, Hillen HS, Höbartner C, Cramer P. Mechanism of molnupiravir-induced SARS-CoV-2 mutagenesis. Nat Struct Mol Biol. 2021; 28 (9): 740–746.
  13. Mohapatra RK, Kuppili S, Suvvari TK, et al. SARS-CoV-2 and its variants of concern including Omicron: A never ending pandemic. Chem Biol Drug Des. 2022; 99 (5): 769–88.
  14. Gushchin VA, Pochtovyi AA, Kustova DD, et al. Dynamics of SARS-CoV-2 Major Genetic Lineages in Moscow in the Context of Vaccine Prophylaxis. Int J Mol Sci. 2022; 23 (23): 14670.
  15. Siniavin AE, Streltsova MA, Nikiforova MA, et al. Snake venom phospholipase A2s exhibit strong virucidal activity against SARS-CoV-2 and inhibit the viral spike glycoprotein interaction with ACE2. Cell Mol Life Sci. 2021; 78 (23): 7777–94.
  16. Driouich JS, Cochin M, Lingas G, et al. Favipiravir antiviral efficacy against SARS-CoV-2 in a hamster model. Nat Commun. 2021; 12 (1): 1735.
  17. Abdelnabi R, Foo CS, Kaptein SJ, et al. The combined treatment of Molnupiravir and Favipiravir results in a potentiation of antiviral efficacy in a SARS-CoV-2 hamster infection model. EBioMedicine. 2021; 72: 103595.
  18. 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): 269–71.
  19. Sheahan TP, Sims AC, Zhou S, et al. An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice. Sci Transl Med. 2020; 12 (541): eabb5883.
  20. Rosenke K, Okumura A, Lewis MC, Feldmann F, Meade-White K, Bohler WF, Griffin A, Rosenke R, Shaia C, A Jarvis MA, Feldmann H. Molnupiravir inhibits SARS-CoV-2 variants including Omicron in the hamster model. JCI Insight. 2022; 7 (13): e160108.
  21. Yuan S, Ye ZW, Liang R, et al. Pathogenicity, transmissibility, and fitness of SARS-CoV-2 Omicron in Syrian hamsters. Science. 2022; 377 (6604): 428–33.