Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding.
2019 新型冠状病毒的基因组特征流行病学学: 病毒起源和受体结合的意义。
- 作者列表："Lu R","Zhao X","Li J","Niu P","Yang B","Wu H","Wang W","Song H","Huang B","Zhu N","Bi Y","Ma X","Zhan F","Wang L","Hu T","Zhou H","Hu Z","Zhou W","Zhao L","Chen J","Meng Y","Wang J","Lin Y","Yuan J","Xie Z","Ma J","Liu WJ","Wang D","Xu W","Holmes EC","Gao GF","Wu G","Chen W","Shi W","Tan W
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.
背景: 在 2019 年 12 月下旬，中国武汉报道了因一种不明微生物导致病毒性肺炎的患者。一个新型冠状病毒随后被确定为致病病原体，暂时命名为 2019新型冠状病毒(2019-nCoV) 的新型冠状病毒 (2019-nCoV)。截至 2020 年 1 月 26 日，已确诊 2000 例nCoV感染病例超过 2019 例，其中大部分涉及居住或访问武汉的人群，已确诊人传人。 方法: 我们对 9 例住院患者的支气管肺泡灌洗液标本和培养分离株进行了新一代测序，其中 8 例曾去过武汉华南海鲜市场。从这些个体获得了完整和部分 2019-nCoV基因组序列。使用Sanger测序连接病毒contigs，获得全长基因组，通过cDNA末端快速扩增确定末端区域。系统发育分析的这 2019 新型冠状病毒基因组和其他电晕病毒es确定进化史的病毒，并帮助推测它可能起源.进行了同源建模，以探索病毒可能的受体结合特性。 结果: 从 9 例患者中获得的 2019-nCoV的 10 个基因组序列极其相似，表现出 99 · 98% 以上的序列同源性。值得注意的是，2019-nCoV与 2018 年在舟山收集的两种蝙蝠衍生的严重急性呼吸综合征 (传染性非典型肺炎) 样冠状病毒bat-SL-CoVZC45 和bat-SL-CoVZXC21 密切相关 (88% 同一性)，中国东部，但更远离传染性非典型肺炎冠状病毒 (约 79%) 和中东呼吸综合征冠状病毒 (约 50%).系统发育分析表明，2019 的新型冠状病毒属于亚属Sarbecovirus属的Betacoronavirus，具有相对长的枝条长度与其近亲bat-SL-CoVZC45 和bat-SL-CoVZXC21，在遗传上不同的从传染性非典型肺炎-CoV.值得注意的是，同源建模揭示了 2019-nCoV具有与传染性非典型肺炎-CoV相似的受体结合域结构，尽管在一些关键残基上存在氨基酸变异。 解释: 2019-nCoV与传染性非典型肺炎-CoV有足够的差异，被认为是一种新的人类感染的 β 病毒。虽然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，但武汉海鲜市场出售的一种动物可能代表了促进病毒在人类中出现的中间宿主。重要的是，结构分析表明 2 019-nCoV可能能够与人类的血管紧张素转换酶 2 受体结合。这种病毒的未来进化、适应和传播需要紧急调查。 基金资助: 国家重点研发计划，国家传染病防控重大专项，中国科学院，山东第一医科大学。
METHODS::Since mid-December of 2019, coronavirus disease 2019 (COVID-19) infection has been spreading from Wuhan, China. The confirmed COVID-19 patients in South Korea are those who came from or visited China. As secondary transmissions have occurred and the speed of transmission is accelerating, there are rising concerns about community infections. The 54-year old male is the third patient diagnosed with COVID-19 infection in Korea. He is a worker for a clothing business and had mild respiratory symptoms and intermittent fever in the beginning of hospitalization, and pneumonia symptoms on chest computerized tomography scan on day 6 of admission. This patient caused one case of secondary transmission and three cases of tertiary transmission. Hereby, we report the clinical findings of the index patient who was the first to cause tertiary transmission outside China. Interestingly, after lopinavir/ritonavir (Kaletra, AbbVie) was administered, β-coronavirus viral loads significantly decreased and no or little coronavirus titers were observed.
METHODS::In December 2019, a novel coronavirus (2019-nCoV) caused an outbreak in Wuhan, China, and soon spread to other parts of the world. It was believed that 2019-nCoV was transmitted through respiratory tract and then induced pneumonia, thus molecular diagnosis based on oral swabs was used for confirmation of this disease. Likewise, patient will be released upon two times of negative detection from oral swabs. However, many coronaviruses can also be transmitted through oral-fecal route by infecting intestines. Whether 2019-nCoV infected patients also carry virus in other organs like intestine need to be tested. We conducted investigation on patients in a local hospital who were infected with this virus. We found the presence of 2019-nCoV in anal swabs and blood as well, and more anal swab positives than oral swab positives in a later stage of infection, suggesting shedding and thereby transmitted through oral-fecal route. We also showed serology test can improve detection positive rate thus should be used in future epidemiology. Our report provides a cautionary warning that 2019-nCoV may be shed through multiple routes.
METHODS::There is a current worldwide outbreak of a new type of coronavirus (2019-nCoV), which originated from Wuhan in China and has now spread to 17 other countries. Governments are under increased pressure to stop the outbreak spiraling into a global health emergency. At this stage, preparedness, transparency, and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak sites and from laboratories supporting the investigation. This paper aggregates and consolidates the virology, epidemiology, clinical management strategies from both English and Chinese literature, official news channels, and other official government documents. In addition, by fitting the number of infections with a single-term exponential model, we report that the infection is spreading at an exponential rate, with a doubling period of 1.8 days.