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《MedRxiv，3月13日，Virus strain of a mild COVID-19 patient in Hangzhou representing a new trend in SARS-CoV-2 evolution related to Furin cleavage site》

  • 来源专题：COVID-19科研动态监测
  • 编译者： zhangmin
  • 发布时间：2020-03-14

  • Virus strain of a mild COVID-19 patient in Hangzhou representing a new trend in SARS-CoV-2 evolution related to Furin cleavage site

    Jin Xi, Kangli Xu, Penglei Jiang, Jiangshan Lian, Shaorui Hao, Hongyu Jia, Hangping Yao, Yimin Zhang, Ruoheng Zheng, Dong Chen, Jinmei Yao, Jianhua Hu, Jianguo Gao, Jian Shen, Liang Wen, Yue Ren, Guodong Yu, Xiaoyan Wang, Yingfeng Lu, Xiaopeng Yu, Liang Yu, Dairong Xiang, Lin Zheng, Nanping Wu, Xiangyun Lu, Linfang Cheng, Fumin Liu, Haibo Wu, Changzhong Jin, Xiaofeng Yang, Pengxu Qian, Yunqing Qiu, Jifang Sheng, Tingbo Liang, Lanjuan Li, Yida Yang

    doi: https://doi.org/10.1101/2020.03.10.20033944

    Abstract

    We found, in our 788 confirmed COVID-19 patients, the decreased rate of severe/critical type, increased liver/kidney damage and prolonged period of nuclear acid positivity during virus dissemination, when compared with Wuhan. To investigate the underlining mechanism, we isolated one strain of SARS- CoV-2 (ZJ01) in mild COVID-19 patient and found the existence of 35 specific gene mutation by gene alignment. Further phylogenetic analysis and RSCU heat map results suggested that ZJ01 may be a potential evolutionary branch of SARS-CoV-2. We classified 54 strains of viruses worldwide (C/T type) based on the base (C or T) at positions 8824 and 28247.

    *注，本文为预印本论文手稿，是未经同行评审的初步报告，其观点仅供科研同行交流，并不是结论性内容，请使用者谨慎使用.

  • 原文来源：https://www.medrxiv.org/content/10.1101/2020.03.10.20033944v1
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  • 《Nature，1月25日，Loss of furin cleavage site attenuates SARS-CoV-2 pathogenesis》
    • 来源专题：COVID-19科研动态监测
    • 编译者：zhangmin
    • 发布时间：2021-02-22
    • Loss of furin cleavage site attenuates SARS-CoV-2 pathogenesis Bryan A. Johnson, Xuping Xie, […]Vineet D. Menachery Nature (2021) Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—a new coronavirus that has led to a worldwide pandemic1—has a furin cleavage site (PRRAR) in its spike protein that is absent in other group-2B coronaviruses2. To explore whether the furin cleavage site contributes to infection and pathogenesis in this virus, we generated a mutant SARS-CoV-2 that lacks the furin cleavage site (ΔPRRA). Here we report that replicates of ΔPRRA SARS-CoV-2 had faster kinetics, improved fitness in Vero E6 cells and reduced spike protein processing, as compared to parental SARS-CoV-2. However, the ΔPRRA mutant had reduced replication in a human respiratory cell line and was attenuated in both hamster and K18-hACE2 transgenic mouse models of SARS-CoV-2 pathogenesis. Despite reduced disease, the ΔPRRA mutant conferred protection against rechallenge with the parental SARS-CoV-2. Importantly, the neutralization values of sera from patients with coronavirus disease 2019 (COVID-19) and monoclonal antibodies against the receptor-binding domain of SARS-CoV-2 were lower against the ΔPRRA mutant than against parental SARS-CoV-2, probably owing to an increased ratio of particles to plaque-forming units in infections with the former. Together, our results demonstrate a critical role for the furin cleavage site in infection with SARS-CoV-2 and highlight the importance of this site for evaluating the neutralization activities of antibodies.
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  • 《3月13日_杭州某轻度COVID-19患者的病毒株代表的SARS-CoV-2中与弗林蛋白酶切割位点有关的进化新趋势》
    • 来源专题：COVID-19科研动态监测
    • 编译者：xuwenwhlib
    • 发布时间：2020-03-15
    • 3月13日_杭州某轻度COVID-19患者的病毒株代表的SARS-CoV-2中与弗林蛋白酶切割位点有关的进化新趋势 1.时间：2020年3月13日 2.机构或团队：浙江大学，杭州医学院 3.事件概要： medRxiv预印平台于3月13日发表了浙江大学等的题为“Virus strain of a mild COVID-19 patient in Hangzhou representing a new trend in SARS-CoV-2 evolution related to Furin cleavage site”的文章。 研究人员发现，与武汉市相比，浙江省的788例确诊的COVID-19患者中，重症/危重型病毒的发病率降低，肝/肾损伤增加，核酸检测阳性时间延长。研究人员为了探明其机制，在轻度COVID-19患者中分离出了一株SARS-CoV-2（ZJ01），并通过基因比对发现了35个特异性基因突变的存在。进一步的系统发育分析和RSCU热图结果表明，ZJ01可能是SARS-CoV-2的潜在进化分支。研究人员根据8824和28247位点的碱基（C或T）对全球54个病毒株（C/T类型）进行了分类。研究人员发现ZJ01在这两个位置均为T，成为目前世界上唯一鉴定出的TT类型。此前，对弗林蛋白酶切割位点（FCS）的预测和病毒家族的序列比对表明，FCS可能是冠状病毒进化的重要位点。ZJ01在FCS（F1-2）附近存在突变，导致S蛋白表面的结构和静电分布发生变化，进一步影响了弗林蛋白酶的结合能力。研究人员单细胞测序和ACE2-Furin共表达的结果证实，整个人体内，尤其是在腺体、肝脏、肾脏和结肠中，Furin的含量较高，而FCS可能有助于SARS-CoV-2感染这些器官。而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OC43（FCS序列-PRRA序列的来源）引起的流感，进一步显示了分化为轻度COVID-19亚型的潜力。 *注，本文为预印本论文手稿，是未经同行评审的初步报告，其观点仅供科研同行交流，并不是结论性内容，请使用者谨慎使用。 4.附件： 原文链接：https://www.medrxiv.org/content/10.1101/2020.03.10.20033944v1
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