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January 1, 2017Proceedings of the Japan Academy Series B1,096 citationsOpen Access

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

YFYousuke FurutaTKTakashi KomenoTNTakaaki Nakamura

Key Points

  • To characterize the mechanism of action, biochemical conversion, and broad-spectrum antiviral profile of favipiravir (T-705) across diverse RNA viral families.
  • Screened a chemical library to identify compounds exhibiting selective antiviral activity against influenza virus strains.
  • Evaluated intracellular metabolic conversion into the active metabolite favipiravir-RTP and its interaction with the conserved catalytic domain of viral RNA-dependent RNA polymerase.
  • Favipiravir undergoes intracellular phosphoribosylation into favipiravir ribofuranosyl-5'-triphosphate (favipiravir-RTP), which acts as a substrate to inhibit RNA-dependent RNA polymerase activity.
  • Demonstrated potent antiviral inhibition against a broad range of influenza subtypes, including drug-resistant strains, as well as fatal hemorrhagic fever viruses including arenaviruses, bunyaviruses, and filoviruses.

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.

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Cite This Study

Furuta et al. (2017) studied this question.

synapsesocial.com/papers/69dd6b5980eea7d3f699cc1fhttps://doi.org/10.2183/pjab.93.027
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