Virus strain from a mild COVID-19 patient in Hangzhou represents a new trend in SARS-CoV-2 evolution potentially related to Furin cleavage site
Virus strain from a mild COVID-19 patient in Hangzhou represents a new trend in SARS-CoV-2 evolution potentially related to Furin cleavage site
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DOI：
10.1080/22221751.2020.1781551
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发表时间：
2020-01-01
影响因子：
13.2
通讯作者：
Yang, Yida
中科院分区：
文献类型：
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作者：
Jin, Xi;Xu, Kangli;Yang, Yida
SARS-CoV-2病毒基因组在COVID-19传播过程中的突变尚不清楚。在来自浙江省的788名COVID-19患者中，我们观察到与武汉患者相比，重症/危重病例的比例有所下降。为了探索机制，我们从一名轻度COVID-19患者中分离出一株SARS-CoV-2（ZJ 01）。发现了35个特异性基因突变。系统发育分析和相对同义密码子使用分析表明ZJ 01可能是SARS-CoV-2的一个潜在进化分支。我们根据8824和28247位的碱基（C或T）对54个全球病毒株进行了分类，而ZJ 01在两个位点都有T。对Furin裂解位点的预测和序列比对表明，Furin裂解位点可能是冠状病毒进化的重要位点。ZJ 01在FCS（F1-2）附近的突变引起S表面蛋白的结构和静电分布的变化，进一步影响Furin的结合能力。单细胞测序和ACE 2-Furin共表达结果证实，Furin表达尤其在腺体、肝脏、肾脏和结肠中更高。SARS-CoV-2向FCS形成的进化模式可能导致其临床症状更接近HKU-1和OC 43引起的轻度流感样症状，进一步显示其分化为轻度COVID-19亚型的潜力。
The mutations in the SARS-CoV-2 virus genome during COVID-19 dissemination are unclear. In 788 COVID-19 patients from Zhejiang province, we observed decreased rate of severe/critical cases compared with patients in Wuhan. For mechanisms exploration, we isolated one strain of SARS-CoV-2 (ZJ01) from a mild COVID-19 patient. Thirty-five specific gene mutations were identified. Phylogenetic and relative synonymous codon usage analysis suggested that ZJ01 may be a potential evolutionary branch of SARS-CoV-2. We classified 54 global virus strains based on the base (C or T) at positions 8824 and 28247 while ZJ01 has T at both sites. The prediction of the Furin cleavage site (FCS) and sequence alignment indicated that the FCS may be an important site of coronavirus evolution. ZJ01 mutations identified near the FCS (F1-2) caused changes in the structure and electrostatic distribution of the S surface protein, further affecting the binding capacity of Furin. Single-cell sequencing and ACE2-Furin co-expression results confirmed that the Furin expression was especially higher in glands, liver, kidneys, and colon. The evolutionary pattern of SARS-CoV-2 towards FCS formation may result in its clinical symptom becoming closer to HKU-1 and OC43 caused mild flu-like symptoms, further showing its potential in differentiating into mild COVID-19 subtypes.