What is the mechanism of Favipiravir?

Favipiravir, also known by its brand name Avigan, is an antiviral medication initially developed to treat influenza. However, its versatile mechanism of action has made it a subject of interest for treating other viral infections, including COVID-19. Understanding the mechanism of Favipiravir requires delving into its molecular interactions and biochemical pathways.

Favipiravir is a prodrug, meaning it is administered in an inactive form and metabolized into its active form within the body. Upon administration, Favipiravir is metabolized into Favipiravir-RTP (ribofuranosyl-5’-triphosphate), the active form. This active compound primarily targets the viral RNA-dependent RNA polymerase (RdRp), an enzyme crucial for the replication of RNA viruses.

The process begins when Favipiravir-RTP mimics the natural nucleotide substrates that RdRp uses to synthesize viral RNA. During viral replication, RdRp incorporates Favipiravir-RTP into the elongating RNA strand. However, unlike natural nucleotides, Favipiravir-RTP introduces mutations into the viral RNA. This error-prone process is known as lethal mutagenesis. The accumulation of these mutations ultimately leads to a non-viable viral genome, effectively halting the replication cycle and reducing the viral load in the host.

Favipiravir's ability to induce lethal mutagenesis makes it a broad-spectrum antiviral, effective against a variety of RNA viruses. This includes not only influenza but also other pathogens such as Ebola, Lassa fever, and certain strains of coronaviruses.

An additional aspect of Favipiravir’s mechanism is its selective targeting. While it disrupts viral RdRp, it has minimal impact on human DNA polymerases and RNA polymerases. This selectivity is crucial for its safety profile, as it helps to minimize potential side effects associated with the drug.

Clinical studies and trials have explored Favipiravir’s efficacy and safety for various viral infections. Its use against COVID-19 has garnered significant attention, with mixed but promising results. The drug has been included in multiple therapeutic regimens and emergency use protocols, especially in regions struggling to control viral outbreaks.

In summary, Favipiravir operates through a sophisticated yet targeted mechanism, primarily involving the induction of lethal mutagenesis in viral RNA. By mimicking natural nucleotides and being selectively incorporated into viral RNA by RdRp, it disrupts the replication process of RNA viruses. This targeted approach, combined with its broad-spectrum efficacy, makes Favipiravir a valuable tool in the antiviral pharmacopoeia.