Authors:
Lu, Roujian and Lu, Roujian and Lu, Roujian and Lu, Roujian and Zhao, Xiang and Zhao, Xiang and Liu, Xiufan and Li, Juan and Li, Juan and Li, Juan and Niu, Peihua and Niu, Peihua and Yang, Bo and Yang, Bo and Wu, Honglong and Wu, Honglong and Wu, Honglong and Wang, Wenling and Wang, Wenling and Song, Hao and Song, Hao and Huang, Baoying and Huang, Baoying and Zhu, Na and Zhu, Na and Bi, Yang and Bi, Yuhai and Ma, Xuejun and Ma, Xuejun and Zhan, Faxian and Zhan, Faxian and Wang, Liang and Wang, Liang and Wang, Liang and Wang, Liang and Wang, Liang and Hu, Tao and Hu, Tao and Hu, Tao and Zhou, Hong and Zhou, Hong and Hu, Zhenhong and Hu, Zhenhong and Zhou, Weimin and Zhou, Weimin and Zhao, Li and Zhao, Li and Zhao, Li and Jing, Chen and Chen, Jing and Chen, Jing and Meng, Yujie and Meng, Yao and Wang, Ji and Wang, Ji and Yang, Lin and Lin, Yang and Yuan, Jianying and Yuan, Jianying and Xie, Zhenghua and Xie, Zhihao and Ma, Jinmin and Ma, Jinmin and Liu, William J. and Liu, William J. and Wang, Dayan and Wang, Dayan and Xu, Wenbo and Xu, Wenbo and Holmes, Edward C. and Holmes, Edward C. and Gao, George F. and Gao, George F. and Wu, Guizhen and Wu, Guizhen and Chen, Weijun and Chen, Weijun and Chen, Weijun and Shi, Weifeng and Shi, Weifeng and Tan, Wenjie and Tan, Wenjie and Tan, Wenjie and Tan, Wenjie
Abstract:
Summary Background In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed. Methods We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus. Findings The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99Β·98\% sequence identity. Notably, 2019-nCoV was closely related (with 88\% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79\%) and MERS-CoV (about 50\%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues. Interpretation 2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation. Funding National Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, Chinese Academy of Sciences, Shandong First Medical University.
