ISSN Print 2500–1094
ISSN Online 2542–1204
Bulletin of RSMU
BIOMEDICAL JOURNAL OF PIROGOV UNIVERSITY (MOSCOW, RUSSIA)
ORIGINAL RESEARCH
Efficacy of favipiravir and molnupiravir against novel SARS-CoV-2 variants in vitro and in vivo
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
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The COVID-19 disease pandemic remains a significant global problem, resulting in hundreds of millions of cases and millions of deaths. The search for specific inhibitors of SARS-CoV-2 for the treatment of this infection remains relevant. Drugs such as Favipiravir and Molnupiravir, which exhibit specific antiviral activity against SARS-CoV-2, are already being used to treat patients. However, there is limited evidence of their effectiveness, especially against novel genetic variants of the COVID-19 pathogen. The aim of this study was to investigate the antiviral effect of these drugs using an in vitro experimental model of SARS-CoV-2 infection in Vero E6 cell culture and an animal model of infection using Syrian hamsters. It has been established that Molnupiravir has an inhibitory effect against variants of the SARS-CoV-2 with IC50 values from 16.51 to 7.88 μM in vitro, and reduces the infectious titer of the virus in the lungs of animals by ~1.5 Log10 in vivo, in while Favipiravir shows lower activity and severe toxicity. Dose selection and frequency of use remain unexplored.
Keywords: COVID-19, SARS-CoV-2, antiviral activity, Omicron, Favipiravir, Molnupiravir, antivirals