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

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JAPAN ACAD
DOI: 10.2183/pjab.93.027

关键词

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

资金

  1. NIAID, NIH [NO1-AI-15435, NO1-AI-30048, NO1-AI-30063, NO1-AI-065357, HHSN272201000039I, HHSN272201100019I, U54 AI-065357]

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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 ribofuranosy1-5'-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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