RT Journal Article
SR Electronic
T1 Structure of RNA-dependent RNA polymerase from 2019-nCoV, a major antiviral drug target
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.03.16.993386
DO 10.1101/2020.03.16.993386
A1 Yan Gao
A1 Liming Yan
A1 Yucen Huang
A1 Fengjiang Liu
A1 Yao Zhao
A1 Lin Cao
A1 Tao Wang
A1 Qianqian Sun
A1 Zhenhua Ming
A1 Lianqi Zhang
A1 Ji Ge
A1 Litao Zheng
A1 Ying Zhang
A1 Haofeng Wang
A1 Yan Zhu
A1 Chen Zhu
A1 Tianyu Hu
A1 Tian Hua
A1 Bing Zhang
A1 Xiuna Yang
A1 Jun Li
A1 Haitao Yang
A1 Zhijie Liu
A1 Wenqing Xu
A1 Luke W. Guddat
A1 Quan Wang
A1 Zhiyong Lou
A1 Zihe Rao
YR 2020
UL http://biorxiv.org/content/early/2020/03/17/2020.03.16.993386.abstract
AB A novel coronavirus (2019-nCoV) outbreak has caused a global pandemic resulting in tens of thousands of infections and thousands of deaths worldwide. The RNA-dependent RNA polymerase (RdRp, also named nsp12), which catalyzes the synthesis of viral RNA, is a key component of coronaviral replication/transcription machinery and appears to be a primary target for the antiviral drug, remdesivir. Here we report the cryo-EM structure of 2019-nCoV full-length nsp12 in complex with cofactors nsp7 and nsp8 at a resolution of 2.9-Å. Additional to the conserved architecture of the polymerase core of the viral polymerase family and a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) domain featured in coronaviral RdRp, nsp12 possesses a newly identified β-hairpin domain at its N-terminal. Key residues for viral replication and transcription are observed. A comparative analysis to show how remdesivir binds to this polymerase is also provided. This structure provides insight into the central component of coronaviral replication/transcription machinery and sheds light on the design of new antiviral therapeutics targeting viral RdRp.One Sentence Summary Structure of 2019-nCov RNA polymerase.