Structure of the RNA-dependent RNA polymerase from COVID-19 virus
Structure of the RNA-dependent RNA polymerase from COVID-19 virus
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DOI：
10.1126/science.abb7498
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发表时间：
2020-05-15
期刊：
影响因子：
56.9
通讯作者：
Rao, Zihe
中科院分区：
文献类型：
--
作者：
Gao, Yan;Yan, Liming;Rao, Zihe
新型冠状病毒[严重急性呼吸道综合征-冠状病毒2型（SARS-CoV-2）]爆发，导致2019冠状病毒病（COVID-19）全球大流行，导致全球数万人感染，数千人死亡。RNA依赖性RNA聚合酶[（RdRp），也称为nsp 12]是冠状病毒复制和转录机制的核心组成部分，它似乎是抗病毒药物remdesivir的主要靶点。我们报告了COVID-19病毒全长nsp 12与辅因子nsp 7和nsp 8复合的冷冻电子显微镜结构，分辨率为2.9埃。除了病毒聚合酶家族的聚合酶核心的保守结构之外，nsp 12在其N末端具有新鉴定的b-发夹结构域。比较分析模型显示了remdesivir如何与这种聚合酶结合。该结构为设计靶向病毒RdRp的新的抗病毒治疗剂提供了基础。
A novel coronavirus [severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2)] outbreak has caused a global coronavirus disease 2019 (COVID-19) pandemic, resulting in tens of thousands of infections and thousands of deaths worldwide. The RNA-dependent RNA polymerase [(RdRp), also named nsp12] is the central component of coronaviral replication and transcription machinery, and it appears to be a primary target for the antiviral drug remdesivir. We report the cryo-electron microscopy structure of COVID-19 virus full-length nsp12 in complex with cofactors nsp7 and nsp8 at 2.9-angstrom resolution. In addition to the conserved architecture of the polymerase core of the viral polymerase family, nsp12 possesses a newly identified b-hairpin domain at its N terminus. A comparative analysis model shows how remdesivir binds to this polymerase. The structure provides a basis for the design of new antiviral therapeutics that target viral RdRp.