ANTIVIRAL ACTIVITY OF FAVIPIRAVIR AGAINST NOVEL DELTA AND OMICRON SARS-COV-2 VARIANTS


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Abstract

Objective. To investigate the antiviral activity of favipiravir against different SARS- CoV-2 variants. Materials and methods. The antiviral activity of the drug against three SARS-CoV-2 variants, such as the strains B.1.1, delta, and omicron, in Vero cells was investigated in vitro. The results were assessed from the reduced viral RNA yield in the infected cells by a real-time reverse transcription PCR assay. Results. Favipiravir effectively inhibited the reproduction of SARS-CoV-2, while the inhibitory concentration of EC50 of the drug did not substantially differ between the virus variants within a range of 200-300 ßM for all the strains. Conclusion. Evolutionary changes in the SARS- CoV-2 virus did not have a significant impact on the in vitro activity of the drug, which is maintained against novel SARS-CoV-2 variants.

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About the authors

Kirill L. KRYSHEN

Research and Production Association «Dom Farmatsii» (House of Pharmacy)

Email: kryshen.kl@doclinika.ru
Head, Department of Specific Toxicology and Microbiology Leningrad Region, Russia

Viktor P. VOLOK

M.P. Chumakov Federal Research Center for Testing and Designing Immunobiologicals Russian Academy of Sciences

Email: volok_vp@chumakovs.su
Junior Researcher, Laboratory of Poliomyelitis and Other Enteroviral Infections with the WHO Reference Center for Poliomyelitis Surveillance, Department of Actual and Re-Emerging Infections with Pandemic Potential, (Institute of Poliomyelitis) Moscow, Russia

Elena Yu. SHUSTOVA

M.P. Chumakov Federal Research Center for Testing and Designing Immunobiologicals Russian Academy of Sciences

Email: shustova_eu@chumakovs.su
Researcher, Laboratory of Poliomyelitis and Other Enteroviral Infections with the WHO Reference Center for Poliomyelitis Surveillance, Department of Actual and Re-Emerging Infections with Pandemic Potential, (Institute of Poliomyelitis) Moscow, Russia

Georgi A. SHIPUNOV

AO «R-Farm»

Email: shipunov@rpharm.ru
Specialist, Department of Preclinical Tests Moscow, Russia

A. V ZINCHENKO

AO «R-Farm»

Moscow, Russia

Mikhail Yu. SAMSONOV

AO «R-Farm»

Email: shipunov@rpharm.ru
Cand. Med. Sci., Medical Director Moscow, Russia

Olga V. FILON

AO «R-Farm»

Email: ov.filon@rpharm.ru
Director, Department for Preclinical and Clinical Development Moscow, Russia

Elena V. SHIPAEVA

AO «R-Farm»

Email: shipaeva@rpharm.ru
Cand. Med. Sci., Head, Department of Preclincal Tests Moscow, Russia

References

  1. Kupriyanov S.V., Semenova Y.V., Semenova L.M. New Coronavirus Infection. Today’S View of the Pandemic. Acta medica Eurasica 2021; (3): 48-59. doi: 10.47026/2413-4864-2021-3-48-59
  2. Sangawa H., Komeno T., Nishikawa H., Yoshida A., Takahashi K., Nomura N. et al. Mechanism of action of T-705 ribosyl triphosphate against influenza virus RNA polymerase. Antimicrob. Agents Chemother. 2013; 57(11): 5202-8.
  3. Jin Z., Smith L.K., Rajwanshi V.K., Kim B., Deval J. The ambiguous base-pairing and high substrate efficiency of T-705 (Favipiravir) Ribofuranosyl 5’-triphosphate towards influenza A virus polymerase. PLoS One 2013; 8(7): e68347.
  4. Baranovich T., Wong S.-S., Armstrong J., Marjuki H., Webby R.J,. Webster R.G. et al. T-705 (favipiravir) induces lethal mutagenesis in influenza A H1N1 viruses in vitro. J. Virol. 2013; 87(7): 3741-51.
  5. Escribano-Romero E., Jiménez de Oya N., Domingo E., Saiz J.C. Extinction of West Nile Virus by Favipiravir through Lethal Mutagenesis. Antimicrob. Agents Chemother. 2017; 61(11): e01400-17. doi: 10.1128/AAC.01400-17
  6. de Âvila A.I., Gallego I., Soria M.E., Gregori J., Quer J., Esteban J.I. et al. Lethal Mutagenesis of Hepatitis C Virus Induced by Favipiravir. PLoS One 2016; 11(10): e0164691-e016461. https://pubmed.ncbi.nlm.nih.gov/27755573
  7. Julander J.G., Shafer K., Smee D.F., Morrey J.D., Furuta Y. Activity of T-705 in a hamster model of yellow fever virus infection in comparison with that of a chemically related compound, T-1106. Antimicrob. Agents Chemother. 2009; 53(1): 202-9.
  8. Gowen B.B., Wong M.-H., Jung K.-H., Sanders A.B., Mendenhall M., Bailey K.W. et al. In vitro and in vivo activities of T-705 against arenavirus and bunyavirus infections. Antimicrob. Agents Chemother. 2007; 51(9): 3168-76.
  9. Mendenhall M., Russell A., Juelich T., Messina.EL., Smee D.F., Freiberg A.N. et al. T-705 (favipiravir) inhibition of arenavirus replication in cell culture. Antimicrob. Agents Chemother. 2011; 55(2): 782-7.
  10. Rocha-Pereira J., Jochmans D., Dallmeier K., Leyssen P., Nascimento M.S.J., Neyts J. Favipiravir (T-705) inhibits in vitro norovirus replication. Biochem. Biophys. Res.Commun. 2012; 424(4): 777-80.
  11. Shannon A., Selisko B., Le N.-TT., Huchting J., Touret F., Piorkowski G. et al. Rapid incorporation of Favipiravir by the fast and permissive viral RNA polymerase complex results in SARS-CoV-2 lethal mutagenesis. Nat.Commun. 2020; 11(1): 4682. https://doi.org/10.1038/s41467-020-18463-z
  12. Driouich J.-S, Cochin M., Lingas G., Moureau G., Touret F., Petit P.-R. et al. Favipiravir antiviral efficacy against SARS- CoV-2 in a hamster model. Nat.Commun. 2021; 12(1): 1735. https://doi.org/10.1038/s41467-021-21992-w
  13. Wang M., Cao R., Zhang L., Yang X., Liu J., Xu M. et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020; 30(3): 269-71. https://doi.org/10.1038/s41422-020-0282-0
  14. Jeon S., Ko M., Lee J., Choi I., Byun S.Y., Park S. et al. Identification of Antiviral Drug Candidates against SARS-CoV-2 from FDA-Approved Drugs. Antimicrob. Agents Chemother. 2020; 64(7): e00819-20. doi: 10.1128/AAC.00819-20
  15. Kaptein S.J.F., Jacobs S., Langendries L., Seldeslachts L., Ter Horst S., Liesenborghs L. et al. Favipiravir at high doses has potent antiviral activity in SARS-CoV-2-infected hamsters, whereas hydroxychloroquine lacks activity. Proc. Nat. Acad. Sci. USA 2020; 117(43): 26955-65. doi: 10.1073/pnas.2014441117
  16. Ruzhentsova T.A., Oseshnyuk R.A., Soluyanova T.N., Dmitrikova E.P., Mustafaev D.M., Pokrovskiy K.A. et al. Phase 3 trial of coronavir (favipiravir) in patients with mild to moderate COVID-19. Am. J. Transl. Res. 2021; 13(11): 12575-87. https://pubmed.ncbi.nlm.nih.gov/34956474
  17. Ivashchenko A.A., Dmitriev K.A., Vostokova N.V., Azarova V.N., Blinow A.A., Egorova A.N. et al. Avifavir for Treatment of Patients With Moderate Coronavirus Disease 2019 (COVID-19): Interim Results of a Phase II/III Multicenter Randomized Clinical Trial. Clin. Infect. Dis. an Off. Publ. Infect. Dis. Soc. Am. 2021; 73(3): 531-4. doi: 10.1093/cid/ciaa1176
  18. Shinkai M., Tsushima K., Tanaka S., Hagiwara E., Tarumoto N., Kawada I. et al. Efficacy and Safety of Favipiravir in Moderate COVID-19 Pneumonia Patients without Oxygen Therapy: A Randomized, Phase III. Clinical Trial. Infect. Dis. Ther. 2021; 10(4): 2489-509. doi: 10.1007/s40121-021-00517-4
  19. Manabe T., Kambayashi D., Akatsu H., Kudo K. Favipiravir for the treatment of patients with COVID-19: a systematic review and meta-analysis. BMC Infect. Dis. 2021; 21(1): 489. doi: 10.1186/s12879-021-06164-x
  20. Hassanipour S., Arab-Zozani M., Amani B., Heidarzad F., Fathalipour M., Martinez-de-Hoyo R. The efficacy and safety of Favipiravir in treatment of COVID-19: a systematic review and meta-analysis of clinical trials. Sci. Rep. 2021; 11(1): 11022. doi: 10.1038/s41598-021-90551-6
  21. Finberg R.W., Ashraf M., Julg B., Ayoade F., Marathe J.G., Issa N.C. et al. US201 Study: A Phase 2, Randomized Proof-of-Concept Trial of Favipiravir for the Treatment of COVID-19. Open. Forum Infect Dis. 2021; 8(12): 563. doi: 10.1093/ofid/ofab563
  22. Временные методические рекомендации Минздрава России «Профилактика, диагностика и лечение новой коронавирусной инфекции (COVID-19)». М., 2021; версия 14. 233 с. https://base.garant.ru/403310712/?
  23. Ömeroglu Ş.K., Temel F., Altun D., Öztop B. Effects of hydroxychloroquine and favipiravir on clinical course in outpatients with COVID-19. Turkish J. Med. Sci. 2021; 51(6): 2827-34. doi: 10.3906/sag-2101-146
  24. Bosaeed M., Alharbi A., Mahmoud E., Alrehily S., Bahlaq M., Gaifer Z. et al. Efficacy of favipiravir in adults with mild COVID-19: a randomized, double-blind, multicentre, placebocontrolled clinical trial. Clin. Microbiol. Infect. 2022. https://www.sciencedirect.com/science/article/pii/S1198743X21007345
  25. https://www.appilitherapeutics.com/newsfeed/Appili-Therapeutics-Provides-Update-on-Phase-3-PRESECO-Clinical-Trial-Evaluating-Avigan%C2% AE%2FReeqonus%E2%84%A2
  26. Solaymani-Dodaran M., Ghanei M., Bagheri M., Qazvini A., Vahedi E., Hassan Saadat S. et al. Safety and efficacy of Favipiravir in moderate to severe SARS-CoV-2 pneumonia.Int Immunopharmacol. 2021; 95: 107522. doi: 10.1016/j.intimp.2021.107522
  27. Case J.B., Bailey A.L., Kim A.S., Chen R.E., Diamond M.S. Growth, detection, quantification, and inactivation of SARS-CoV-2. Virology 2020; 548: 39-48. https://pubmed.ncbi.nlm.nih.gov/32838945
  28. Jureka A.S., Silvas J.A., Basler C.F. Propagation, Inactivation, and Safety Testing of SARS-CoV-2. Viruses 2020; 12(6): 622 doi: 10.3390/v12060622
  29. Bojkova D., Widera M., Ciesek S., Wass M.N., Michaelis M., Cinatl J. Reduced interferon antagonism but similar drug sensitivity in Omicron variant compared to Delta variant of SARS-CoV-2 isolates. Cell Res. 2022. https://doi.org/10.1038/s41422-022-00619-9
  30. Tomita Y., Takeda M., Matsuyama S. The anti-influenza virus drug favipiravir has little effect on replication of SARS-CoV-2 in cultured cells. Antimicrobial agents and chemotherapy. 2021; 65: e00020-21 doi: 10.1128/AAC.00020-21
  31. Takashita E., Kinoshita N., Yamayoshi S., Sakai-Tagawa Y., Fujisaki S., Ito M. et al. Efficacy of Antibodies and Antiviral Drugs against Covid-19 Omicron Variant. New Engl. J. Med. 2022. 386(10): 995-8. doi: 10.1056/NEJMc2119407
  32. Vangeel L., Chiu W., De Jonghe S., Maes P., Slechten B., Raymenants J. et al. Remdesivir, Molnupiravir and Nirmatrelvir remain active against SARS-CoV-2 Omicron and other variants of concern. Antiviral Res. 2022; 198: 105252. doi: 10.1016/j. antiviral.2022.105252
  33. Wang Y., Zhong W., Salam A., Tarning J., Zhan Q., Huang J.-A. et al. Phase 2a, open-label, dose-escalating, multi-center pharmacokinetic study of favipiravir (T-705) in combination with oseltamivir in patients with severe influenza. EBioMedicine 2020; 62: 103125. http://europepmc.org/abstract/ MED/33232871
  34. Irie K., Nakagawa A., Fujita H., Tamura R., Eto M., Ikesue H. et al. Pharmacokinetics of Favipiravir in Critically Ill Patients With COVID-19. Clin. Trans. Sci. 2020; 13(5): 880-5. doi: 10.1111/ cts.12827
  35. Du Y.-X., Chen X.-P. Favipiravir: Pharmacokinetics and Concerns About Clinical Trials for 2019-nCoV Infection. Clin. Pharmacol. Ther. 2020; 108(2): 242-7. doi: 10.1002/cpt.1844
  36. Arshad U., Pertinez H., Box H., Tatham L., Rajoli R.K.R., Curley P. et al. Prioritization of Anti-SARS-Cov-2 Drug Repurposing Opportunities Based on Plasma and Target Site Concentrations Derived from their Established Human Pharmacokinetics. Clin. Pharmacol. Ther. 2020; 108(4): 775-90. doi: 10.1002/cpt.1909
  37. Pertinez H., Rajoli K.R., Khoo S.H., Owen A. Pharmacokinetic modelling to estimate intracellular favipiravir ribofuranosyl-5’-triphosphate exposure to support posology for SARS-CoV-2. J. Antimicrob. Chemother. 2021; 76 (Suppl 1). doi: 10.1093/jac/ dkab135

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