Departamento de Biotecnología, INIA, Madrid, Spain.
Departamento de Virología y Microbiología, Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Madrid, Spain.
Antimicrob Agents Chemother. 2017 Oct 24;61(11). doi: 10.1128/AAC.01400-17. Print 2017 Nov.
Favipiravir is an antiviral agent effective against several RNA viruses. The drug has been shown to protect mice against experimental infection with a lethal dose of West Nile virus (WNV), a mosquito-borne flavivirus responsible for outbreaks of meningitis and encephalitis for which no antiviral therapy has been licensed; however, the mechanism of action of the drug is still not well understood. Here, we describe the potent antiviral activity of favipiravir against WNV, showing that it decreases virus-specific infectivity and drives the virus to extinction. Two passages of WNV in the presence of 1 mM favipiravir-a concentration that is more than 10-fold lower than its 50% cytotoxic concentration (CC)-resulted in a significant increase in mutation frequency in the mutant spectrum and in a bias toward A→G and G→A transitions relative to the population passaged in the absence of the drug. These data, together with the fact that the drug is already licensed in Japan against influenza virus and in a clinical trial against Ebola virus, point to favipiravir as a promising antiviral agent to fight medically relevant flaviviral infections, such as that caused by WNV.
法匹拉韦是一种针对多种 RNA 病毒有效的抗病毒药物。该药物已被证明可保护小鼠免受西尼罗河病毒（WNV）致死剂量的实验性感染，WNV 是一种由蚊子传播的黄病毒，可引起脑膜炎和脑炎爆发，目前尚无获得许可的抗病毒疗法；然而，该药物的作用机制仍未得到很好的理解。在这里，我们描述了法匹拉韦对 WNV 的强大抗病毒活性，表明它降低了病毒的特异性感染力，并促使病毒灭绝。在 1mM 法匹拉韦存在下对 WNV 进行两次传代，该浓度比其 50%细胞毒性浓度（CC）高 10 多倍，导致突变频率在突变谱中显著增加，并且相对于未用药传代的群体，偏向于 A→G 和 G→A 转换。这些数据，再加上该药物已在日本获得针对流感病毒的许可，并在针对埃博拉病毒的临床试验中，表明法匹拉韦是一种有前途的抗病毒药物，可用于治疗与医学相关的黄病毒感染，如由 WNV 引起的感染。
