Furuta Yousuke, Komeno Takashi, Nakamura Takaaki
Business Development Department, Toyama Chemical Co., Ltd.
Pharmaceutical and Healthcare Research Laboratories, FUJIFILM Corporation.
Proc Jpn Acad Ser B Phys Biol Sci. 2017;93(7):449-463. doi: 10.2183/pjab.93.027.
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.
法匹拉韦(T-705;6-氟-3-羟基-2-吡嗪甲酰胺)是一种抗病毒药物,可选择性且强效地抑制RNA病毒的RNA依赖性RNA聚合酶(RdRp)。法匹拉韦由富山化学株式会社通过筛选化学文库对流感病毒的抗病毒活性而发现。法匹拉韦在细胞内进行磷酸核糖基化成为活性形式法匹拉韦-RTP(法匹拉韦呋喃核糖基-5'-三磷酸),其被RdRp识别为底物,并抑制RNA聚合酶活性。由于RdRp的催化结构域在各种类型的RNA病毒中保守,这种作用机制支撑了法匹拉韦更广泛的抗病毒活性谱。法匹拉韦对多种类型和亚型的流感病毒有效,包括对现有抗流感药物耐药的毒株。值得注意的是,法匹拉韦对其他RNA病毒如沙粒病毒、布尼亚病毒和丝状病毒具有抗病毒活性,所有这些病毒都已知会引起致命性出血热。这些独特的抗病毒特性将使法匹拉韦成为针对特定不可治疗的RNA病毒感染的潜在有前景的药物。