Yan Gao 1 , 2 , Liming Yan 1 , Yucen Huang 1 , Fengjiang Liu 2 , Yao Zhao 2 , Lin Cao 3 , Tao Wang 1 , Qianqian Sun 2 , Zhenhua Ming 4 , Lianqi Zhang 1 , Ji Ge 1 , Litao Zheng 1 , Ying Zhang 1 , Haofeng Wang 2 , 5 , Yan Zhu 2 , Chen Zhu 2 , Tianyu Hu 2 , Tian Hua 2 , Bing Zhang 2 , Xiuna Yang 2 , Jun Li 2 , Haitao Yang 2 , Zhijie Liu 2 , Wenqing Xu 2 , Luke W. Guddat 6 , Quan Wang 2 , † , Zhiyong Lou 1 , † , Zihe Rao 1 , 2 , 3 , 7 , †
10 April 2020
A novel coronavirus (COVID-19 virus) 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) is the central component of coronaviral replication/transcription machinery and appears to be a primary target for the antiviral drug, remdesivir. We report the cryo-EM structure of COVID-19 virus full-length nsp12 in complex with cofactors nsp7 and nsp8 at 2.9-Å resolution. In addition to the conserved architecture of the polymerase core of the viral polymerase family, nsp12 possesses a newly identified β-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 targeting viral RdRp.