Author: Yan Gao; Liming Yan; Yucen Huang; Fengjiang Liu; Yao Zhao; Lin Cao; Tao Wang; Qianqian Sun; Zhenhua Ming; Lianqi Zhang; Ji Ge; Litao Zheng; Ying Zhang; Haofeng Wang; Yan Zhu; Chen Zhu; Tianyu Hu; Tian Hua; Bing Zhang; Xiuna Yang; Jun Li; Haitao Yang; Zhijie Liu; Wenqing Xu; Luke W. Guddat; Quan Wang; Zhiyong Lou; Zihe Rao
Title: Structure of RNA-dependent RNA polymerase from 2019-nCoV, a major antiviral drug target Document date: 2020_3_17
ID: glfxrla9_3
Snippet: CoVs employ a multi-subunit replication/transcription machinery, being assembled by a set of non-structural proteins (nsp) produced as cleavage products of the ORF1a and ORF1ab viral polyproteins (5) to facilitate virus replication and transcription. A key component, the RNA-10 dependent RNA polymerase (nsp12), catalyzes the synthesis of viral RNA and thus plays a central role in the replication and transcription cycle of 2019-nCoV, possibly with.....
Document: CoVs employ a multi-subunit replication/transcription machinery, being assembled by a set of non-structural proteins (nsp) produced as cleavage products of the ORF1a and ORF1ab viral polyproteins (5) to facilitate virus replication and transcription. A key component, the RNA-10 dependent RNA polymerase (nsp12), catalyzes the synthesis of viral RNA and thus plays a central role in the replication and transcription cycle of 2019-nCoV, possibly with the assistance of nsp7 and nsp8 as co-factors (5, 6). Therefore, nsp12 is a primary target for the nucleotide analog antiviral inhibitors, e.g. remdesivir which shows potential to treat 2019-nCoV infections (7, 8) . To inform drug design we have determined the structure of nsp12, in complex with its cofactors nsp7 15 and nsp8 by cryo-Electron Microscopy (Cryo-EM) using two different protocols, one in the absence of DTT (Dataset-1) and the other in the presence of DTT (Dataset-2).
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