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

被引:740
作者
Furuta, Yousuke [1 ]
Komeno, Takashi [2 ]
Nakamura, Takaaki [3 ]
机构
[1] Toyama Chem Co Ltd, Business Dev Dept, 4-1,Shimookui 2-chome, Toyama 9308508, Japan
[2] FUJIFILM Corp, Pharmaceut & Healthcare Res Labs, Toyama, Japan
[3] Toyama Chem Co Ltd, Res Labs, Toyama, Japan
来源
PROCEEDINGS OF THE JAPAN ACADEMY SERIES B-PHYSICAL AND BIOLOGICAL SCIENCES | 2017年 / 93卷 / 07期
关键词
favipiravir; broad spectrum anti-viral agent; influenza virus; RNA viruses; RNA-dependent RNA polymerase; viral hemorrhagic fever; EBOLA-VIRUS DISEASE; ORALLY-ADMINISTERED T-705; INFLUENZA-A VIRUSES; IN-VIVO ACTIVITIES; LASSA FEVER; MOUSE MODEL; HEMORRHAGIC-FEVER; THROMBOCYTOPENIA SYNDROME; LETHAL MUTAGENESIS; EFFICACY;
D O I
10.2183/pjab.93.027
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
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页码:449 / 463
页数:15
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