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Lancet. 2020 Jan 30. pii: S0140-6736(20)30251-8. doi: 10.1016/S0140-6736(20)30251-8. [Epub ahead of print]

Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding.

Author information

1
NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
2
Key Laboratory of Etiology and Epidemiology of Emerging Infectious Diseases in Universities of Shandong, Shandong First Medical University and Shandong Academy of Medical Sciences, Tai'an, China.
3
Division for Viral Disease Detection, Hubei Provincial Center for Disease Control and Prevention, Wuhan, China.
4
BGI PathoGenesis Pharmaceutical Technology, Shenzhen, China.
5
Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China.
6
Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China; Center for Influenza Research and Early-warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Diseases (CEEID), Chinese Academy of Sciences, Beijing, China.
7
Central Theater, People's Liberation Army General Hospital, Wuhan, China.
8
Key Laboratory of Laboratory Medicine, Ministry of Education, and Zhejiang Provincial Key Laboratory of Medical Genetics, Institute of Medical Virology, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China.
9
Marie Bashir Institute for Infectious Diseases and Biosecurity, School of Life and Environmental Sciences and School of Medical Sciences, University of Sydney, Sydney, NSW, Australia.
10
NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China; Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China; Center for Influenza Research and Early-warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Diseases (CEEID), Chinese Academy of Sciences, Beijing, China.
11
Key Laboratory of Etiology and Epidemiology of Emerging Infectious Diseases in Universities of Shandong, Shandong First Medical University and Shandong Academy of Medical Sciences, Tai'an, China; The First Affiliated Hospital of Shandong First Medical University (Shandong Provincial Qianfoshan Hospital), Jinan, China. Electronic address: wfshi@sdfmu.edu.cn.
12
NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China; Central Theater, People's Liberation Army General Hospital, Wuhan, China; Center for Biosafety Mega-Science, Chinese Academy of Sciences, Beijing, China. Electronic address: tanwj@ivdc.chinacdc.cn.

Abstract

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 99·98% 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.

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