Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase

Proc Jpn Acad Ser B Phys Biol Sci. 2017;93(7):449-463. doi: 10.2183/pjab.93.027.

Abstract

Favipiravir (T-705; 6-fluoro-3-hydroxy-2-pyrazinecarboxamide) is an anti-viral agent that selectively and potently inhibits the RNA-dependent RNA polymerase (RdRp) of RNA viruses. Favipiravir was discovered through screening chemical library for anti-viral activity against the influenza virus by Toyama Chemical Co., Ltd. Favipiravir undergoes an intracellular phosphoribosylation to be an active form, favipiravir-RTP (favipiravir ribofuranosyl-5'-triphosphate), which is recognized as a substrate by RdRp, and inhibits the RNA polymerase activity. Since the catalytic domain of RdRp is conserved among various types of RNA viruses, this mechanism of action underpins a broader spectrum of anti-viral activities of favipiravir. Favipiravir is effective against a wide range of types and subtypes of influenza viruses, including strains resistant to existing anti-influenza drugs. Of note is that favipiravir shows anti-viral activities against other RNA viruses such as arenaviruses, bunyaviruses and filoviruses, all of which are known to cause fatal hemorrhagic fever. These unique anti-viral profiles will make favipiravir a potentially promising drug for specifically untreatable RNA viral infections.

Keywords: RNA viruses; RNA-dependent RNA polymerase; broad spectrum anti-viral agent; favipiravir; influenza virus; viral hemorrhagic fever.

Publication types

  • Review

MeSH terms

  • Amides / pharmacology*
  • Animals
  • Antiviral Agents / pharmacology*
  • DNA-Directed RNA Polymerases / antagonists & inhibitors*
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Pyrazines / pharmacology*
  • Viruses / drug effects
  • Viruses / enzymology*

Substances

  • Amides
  • Antiviral Agents
  • Enzyme Inhibitors
  • Pyrazines
  • DNA-Directed RNA Polymerases
  • favipiravir