Structure of the RNA-dependent RNA polymerase from COVID-19 virus

Gao, Yan; Yan, Liming; Huang, Yucen; Liu, Fengjiang; Zhao, Yao; Cao, Lin; Wang, Tao; Sun, Qianqian; Ming, Zhenhua; Zhang, Lianqi; Ge, Ji; Zheng, Litao; Zhang, Ying; Wang, Haofeng; Zhu, Yan; Zhu, Chen; Hu, Tianyu; Hua, Tian; Zhang, Bing; Yang, Xiuna; Li, Jun; Yang, Haitao; Liu, Zhijie; Xu, Wenqing; Guddat, Luke W.; Wang, Quan; Lou, Zhiyong; Rao, Zihe

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.