The Influenza Virus Polymerase Complex: An Update on Its Structure, Functions, and Significance for Antiviral Drug Design.
The Influenza Virus Polymerase Complex: An Update on Its Structure, Functions, and Significance for Antiviral Drug Design.
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流感病毒聚合酶复合物：抗病毒药物设计的结构，功能和重要性的更新。
DOI：
10.1002/med.21401
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发表时间：
2016-11
影响因子：
13.3
通讯作者：
Naesens, Lieve
中科院分区：
文献类型：
--
作者：
Stevaert, Annelies;Naesens, Lieve
流感病毒引起季节性流行病和大流行性爆发，与显著的发病率和死亡率以及巨大的成本相关。由于对现有抗流感药物的耐药性正在上升，迫切需要具有不同作用模式的创新抑制剂。流感聚合酶复合物被广泛认为是一个关键的药物靶标，因为它在病毒复制中起着关键作用，并且在甲型流感（人源或人畜共患）和B型流感病毒中具有高度保守性。我们在这里回顾了近年来在解开这种蛋白质复合物的结构和功能方面取得的主要进展，使结构辅助药物设计能够朝向PA核酸内切酶，PB 1聚合酶或帽结合PB 2亚基的核心区域。或者，抑制剂可以靶向蛋白质-蛋白质相互作用位点、参与病毒RNA合成的细胞因子、病毒RNA本身或病毒核糖核蛋白的核蛋白组分。针对这些不同的药理学靶点所取得的最新进展已经产生了先进的药物（即，法匹拉韦和VX-787）或早期临床试验，此外还有几种处于不同开发阶段的实验性抑制剂，这些都在这里介绍。
Influenza viruses cause seasonal epidemics and pandemic outbreaks associated with significant morbidity and mortality, and a huge cost. Since resistance to the existing anti‐influenza drugs is rising, innovative inhibitors with a different mode of action are urgently needed. The influenza polymerase complex is widely recognized as a key drug target, given its critical role in virus replication and high degree of conservation among influenza A (of human or zoonotic origin) and B viruses. We here review the major progress that has been made in recent years in unravelling the structure and functions of this protein complex, enabling structure‐aided drug design toward the core regions of the PA endonuclease, PB1 polymerase, or cap‐binding PB2 subunit. Alternatively, inhibitors may target a protein–protein interaction site, a cellular factor involved in viral RNA synthesis, the viral RNA itself, or the nucleoprotein component of the viral ribonucleoprotein. The latest advances made for these diverse pharmacological targets have yielded agents in advanced (i.e., favipiravir and VX‐787) or early clinical testing, besides several experimental inhibitors in various stages of development, which are all covered here.
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影响因子：
3.7
作者：
Chase, Geoffrey;Deng, Tao;Brownlee, George
通讯作者：
Brownlee, George
DOI：
10.3390/v2071448
发表时间：
2010-07
期刊：
Viruses
影响因子：
--
作者：
Barik S
通讯作者：
Barik S
影响因子：
16.6
作者：
Cheung, Peter P. H.;Watson, Simon J.;Choy, Ka-Tim;Sia, Sin Fun;Wong, Diana D. Y.;Poon, Leo L. M.;Kellam, Paul;Guan, Yi;Peiris, J. S. Malik;Yen, Hui-Ling
通讯作者：
Yen, Hui-Ling
影响因子：
4
作者：
Bauman, Joseph D.;Patel, Disha;Baker, Steven F.;Vijayan, R. S. K.;Xiang, Amy;Parhi, Ajit K.;Martinez-Sobrido, Luis;LaVoie, Edmond J.;Das, Kalyan;Arnold, Eddy
通讯作者：
Arnold, Eddy
影响因子：
5.4
作者：
Amorim, Maria Joao;Kao, Richard Y.;Digard, Paul
通讯作者：
Digard, Paul