Favipiravir as a potential countermeasure for COVID-19

Abstract

Favipiravir is a broad-spectrum antiviral agent, an analogue of purine nucleosides, licensed as an anti-influenza drug in Japan. Like other analogs of nucleosides, favipiravir acts as a prodrug, and undergoes an intracellular phosphoribosylation to be an active form, favipiravir ribofuranosyl-5'-triphosphate. The metabolite competitively inhibits the activity of RNA polymerase of RNA viruses and prevents virus replication by incorporating into the viral RNA, acting as a chain terminator. It possesses selective or virus-specific intracellular action and low cytotoxicity. Favipiravir inhibits viral RNA synthesis by terminating chain elongation, which re-duces the likelihood of mutations and the emergence of resistant virus strains. Favipiravir causes a significant decrease in pro-inflammatory cytokines levels, which enhances the antiviral effect. Favipiravir demonstrated antiviral activity against a broad spectrum of RNA viruses, such as influenza A, B and C viruses, Ebola virus, Lassa virus, rabies, etc. In 2020, as part of screening testing of antiviral drugs, including favipiravir, it was shown in vitro antiviral activity against 2019-nCoV with better efficacy and selectivity compared to ribavirin. More than 10 clinical trials have been initiated to study the effectiveness of favipiravir for the treatment of mild to moderate COVID-19. A fixed loading and maintenance dose of 3200/1200 mg and 3600/1600 mg was used. The results showed a better clinical effect with earlier elimination of coronavirus, regression of computed tomographic changes and the need for mechanical ventilation in the favipiravir treat-ment groups compared with lopinavir/ritonavir, Arbidol and other drugs. In a Russian phase II/III clinical study of efficacy and safety of favipiravir (Avifavir)(1600/600 mg or 1800/800 mg 2 times a day) vs standard treatment in patients with moderate COVID-19, favipiravir showed virus clearance within 4 days in 62,5% of patients, safety and good tolerance. Favipiravir is included in the Russian guidelines for the treatment of COVID-19 and is the only approved oral med-ication for the treatment of moderate COVID-19 to date.