Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding
Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding
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DOI：
10.1016/s0140-6736(20)30251-8
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发表时间：
2020-02-22
期刊：
影响因子：
168.9
通讯作者：
Tan, Wenjie
中科院分区：
文献类型：
--
作者：
Lu, Roujian;Zhao, Xiang;Tan, Wenjie
背景 2019 年 12 月下旬，中国武汉报告出现因不明微生物病原体导致病毒性肺炎的患者。随后，一种新型冠状病毒被确定为致病病原体，暂时命名为2019新型冠状病毒（2019-nCoV）。截至 2020 年 1 月 26 日，已确诊 2000 多例 2019-nCoV 感染病例，其中大多数涉及在武汉居住或访问过的人，并已确认人传人。 方法 我们对 9 名住院患者的支气管肺泡灌洗液样本和培养分离株进行了二代测序，其中 8 名患者曾到访过武汉华南海鲜市场。从这些人身上获得了完整和部分 2019-nCoV 基因组序列。使用桑格测序连接病毒重叠群以获得全长基因组，并通过 cDNA 末端的快速扩增确定末端区域。对这些 2019-nCoV 基因组和其他冠状病毒基因组的系统发育分析用于确定病毒的进化历史，并帮助推断其可能的起源。通过同源建模来探索该病毒可能的受体结合特性。研究结果从 9 名患者身上获得的 10 条 2019-nCoV 基因组序列极其相似，表现出超过 99.98% 的序列同一性。值得注意的是，2019-nCoV 与 2018 年在中国东部舟山收集的两种蝙蝠来源的严重急性呼吸综合征 (SARS) 样冠状病毒 bat-SL-CoVZC45 和 bat-SL-CoVZXC21 密切相关（具有 88% 的同一性），但与 SARS-CoV（约 79%）和 MERS-CoV（约 50%）的距离更远。系统发育分析显示，2019-nCoV属于乙型冠状病毒属的Sarbecovirus亚属，其分支长度与其最近亲bat-SL-CoVZC45和bat-SL-CoVZXC21相对较长，并且在遗传上与SARS-CoV不同。值得注意的是，同源模型显示，2019-nCoV 具有与 SARS-CoV 相似的受体结合域结构，尽管某些关键残基上存在氨基酸变化。 解释 2019-nCoV 与 SARS-CoV 完全不同，被认为是一种新的人类感染 β 冠状病毒。尽管我们的系统发育分析表明蝙蝠可能是这种病毒的原始宿主，但在武汉海鲜市场出售的一种动物可能代表了促进该病毒在人类中出现的中间宿主。重要的是，结构分析表明 2019-nCoV 可能能够与人类的血管紧张素转换酶 2 受体结合。这种病毒未来的进化、适应和传播值得紧急调查。
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 angiotensinconverting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation.