Structure of RNA-dependent RNA polymerase from 2019-nCoV, a major antiviral drug target

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

The structure of the 2019-nCoV nsp12 contains a "right hand" polymerase domain (residues S367-F920), and a nidovirus-unique N-terminal extension domain (residues D60-R249) adopting a nidovirus RdRp-associated nucleotidyltransferase (NiRAN)(9) architecture, being connected by 30 an interface domain (residues A250-F369) (Figs. 1, A and B). An additional N-terminal β-hairpin (V31-K50) was built with the guidance of an unambiguous cryo-EM map ( fig. S3A ), inserting into the groove clamped by the NiRAN domain and the palm subdomain in the RdRp domain (Fig. 2) . The nsp7-nsp8 pair shows a conserved structure similar to the SARS-CoV nsp7-nsp8 pair (6, 10). The orientation of the N-terminal helix of another individual nsp8 bound to nsp12 is shifted 35 compared with that in the nsp7-nsp8 pair ( fig. S4 ). The polypeptides of nsp12 can be traced in the map, except for S1-V30, T51-S68, H75, K103-V111, D336, T896-S904, F921-Q932, which cannot be observed.