Favipiravir (T-705), a novel viral RNA polymerase inhibitor.
Favipiravir (T-705), a novel viral RNA polymerase inhibitor.
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DOI：
10.1016/j.antiviral.2013.09.015
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发表时间：
2013-11
影响因子：
7.6
通讯作者：
Barnard, Dale L.
中科院分区：
文献类型：
--
作者：
Furuta, Yousuke;Gowen, Brian B.;Takahashi, Kazumi;Shiraki, Kimiyasu;Smee, Donald F.;Barnard, Dale L.
法匹拉韦（T-705; 6-氟-3-羟基-2-吡嗪甲酰胺）是一种选择性抑制流感病毒RNA依赖性RNA聚合酶的抗病毒药物。通过细胞酶将其磷酸核糖基化为活性形式法匹拉韦-呋喃核糖基-5 ′-三磷酸（RTP）。其抗病毒作用因加入嘌呤核酸而减弱，表明病毒RNA聚合酶错误地将法匹拉韦-RTP识别为嘌呤核苷酸。法匹拉韦对多种流感病毒具有活性，包括A（H1N1）pdm 09、A（H5 N1）和最近出现的A（H7 N9）禽流感病毒。它还能抑制对当前抗病毒药物耐药的流感病毒株，并与奥司他韦联用显示出协同效应，从而扩大了流感治疗选择。法匹拉韦治疗流感的III期临床评价已在日本完成，两项II期研究已在美国完成。除了抗流感活性外，法匹拉韦还能阻断许多其他RNA病毒的复制，包括沙粒病毒（朱宁、马丘波和皮钦德）;白蛉病毒（裂谷热、白蛉热和蓬塔托罗）;汉坦病毒（Maporal、Dobrava和前景山）;黄病毒（黄热病和西尼罗河）;肠道病毒（脊髓灰质炎病毒和鼻病毒）;甲病毒，西方马脑炎病毒;副粘病毒，呼吸道合胞病毒;和诺如病毒。由于其独特的作用机制和广泛的抗病毒活性，法匹拉韦是一种很有前途的候选药物，用于治疗流感和许多其他RNA病毒性疾病，目前还没有批准的治疗方法。
Favipiravir (T-705; 6-fluoro-3-hydroxy-2-pyrazinecarboxamide) is an antiviral drug that selectively inhibits the RNA-dependent RNA polymerase of influenza virus. It is phosphoribosylated by cellular enzymes to its active form, favipiravir-ribofuranosyl-5′-triphosphate (RTP). Its antiviral effect is attenuated by the addition of purine nucleic acids, indicating the viral RNA polymerase mistakenly recognizes favipiravir-RTP as a purine nucleotide. Favipiravir is active against a broad range of influenza viruses, including A(H1N1)pdm09, A(H5N1) and the recently emerged A(H7N9) avian virus. It also inhibits influenza strains resistant to current antiviral drugs, and shows a synergistic effect in combination with oseltamivir, thereby expanding influenza treatment options. A Phase III clinical evaluation of favipiravir for influenza therapy has been completed in Japan and two Phase II studies have been completed in the United States. In addition to its anti-influenza activity, favipiravir blocks the replication of many other RNA viruses, including arenaviruses (Junin, Machupo and Pichinde); phleboviruses (Rift Valley fever, sandfly fever and Punta Toro); hantaviruses (Maporal, Dobrava, and Prospect Hill); flaviviruses (yellow fever and West Nile); enteroviruses (polio- and rhinoviruses); an alphavirus, Western equine encephalitis virus; a paramyxovirus, respiratory syncytial virus; and noroviruses. With its unique mechanism of action and broad range of antiviral activity, favipiravir is a promising drug candidate for influenza and many other RNA viral diseases for which there are no approved therapies.
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