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What is Favipiravir?

In the context of the global pandemic COVID-19, new vaccines and drugs were invented to save more lives, one of which is Favipiravir. According to the emedicine.medscape, Favipiravir is an oral antiviral approved for the treatment of influenza in Japan. It selectively inhibits RNA polymerase, which is necessary for viral replication. Japan has commenced with a phase 3 clinical trial.

In the United States, a phase 2 trial will enrol approximately 50 patients with COVID-19, in collaboration with Brigham and Women's Hospital, Massachusetts General Hospital, and the University of Massachusetts Medical School. In India, a phase 3 trial combining 2 antiviral agents, favipiravir and umifenovir, started in May 2020.

How does Favipiravir work?

Biologically, within the tissue, the molecule undergoes phosphoribosylation to favipiravir-RTP, which is the active form of this drug. According to the ncbi.nlm.nih.gov, it exerts its antiviral effect through the following mechanisms:

This molecule acts as a substrate for the RNA-dependent RNA-polymerase (RdRp) enzyme, which is mistaken by the enzyme as a purine nucleotide,2 thus inhibiting its activity leading to termination of viral protein synthesis

It gets incorporated in the viral RNA strand, preventing further extension.5 This mechanism of action, along with the preservation of the catalytic domain of the RdRp enzyme across various RNA viruses, explains the broad spectrum of activity of this drug.

It has recently been shown that favipiravir induces lethal mutagenesis in vitro during influenza virus infection, making it a virucidal drug.6 Whether a similar activity is demonstrated against SARS-CoV-2 or not is uncertain.

Role in SARS-CoV-2

Shannon et al.12 found that the SARS-CoV-2–RDRp complex is at least 10-fold more active than any other viral RdRp known. Favipiravir acts by inhibiting this viral RdRp enzyme, allowing facile insertion of favipiravir into viral RNA while sparing human DNA. They concluded that nucleoside analogues (such as favipiravir) are promising candidates for the treatment of COVID-19.

Clinical trials in COVID-19

Over the past few months, clinical studies have been performed all over the world to assess the efficacy of favipiravir in the management of COVID-19. The major clinical studies have been done in many countries such as China, Japan, the USA, Russia,...etc.

Side effects/adverse effects of Favipiravir

Hyperuricemia

Teratogenicity

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