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《CELL，5月28日，Proteolytic cleavage of the SARS-CoV-2 spike protein and the role of the novel S1/S2 site》

  • 来源专题：COVID-19科研动态监测
  • 编译者： xuwenwhlib
  • 发布时间：2020-05-30

  • Proteolytic cleavage of the SARS-CoV-2 spike protein and the role of the novel S1/S2 site

    Javier A. Jaimes

    Jean K. Millet

    Gary R. Whittaker

    Open AccessPublished:May 28, 2020DOI:https://doi.org/10.1016/j.isci.2020.101212

    Abstract

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 19 (COVID-19) has rapidly spread to the entire world within a few months. The origin of SARS-CoV-2 has been related to the lineage B Betacoronavirus SARS-CoV and SARS-related coronaviruses found in bats. Early characterizations of the SARS-CoV-2 genome revealed the existence of a distinct 4 amino acid insert within the spike (S) protein (underlined, SPRRAR↓S), at the S1/S2 site located at the interface between the S1 receptor binding subunit and the S2 fusion subunit. Notably, this insert appears to be a distinguishing feature among SARS-related sequences and introduces a potential cleavage site for the protease furin. Here, we investigate the potential role of this novel S1/S2 cleavage site and present direct biochemical evidence for proteolytic processing by a variety of proteases. We discuss these findings in the context of the origin of SARS-CoV-2, viral stability and transmission.

  • 原文来源：https://www.cell.com/iscience/fulltext/S2589-0042(20)30397-7
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  • 《Cell，5月10日，A novel bat coronavirus closely related to SARS-CoV-2 contains natural insertions at the S1/S2 cleavage site of the spike protein》
    • 来源专题：COVID-19科研动态监测
    • 编译者：zhangmin
    • 发布时间：2020-05-12
    • A novel bat coronavirus closely related to SARS-CoV-2 contains natural insertions at the S1/S2 cleavage site of the spike protein Hong Zhou ,Xing Chen ,Tao Hu ,Alice C. Hughes, Yuhai Bi, Weifeng Shi Published:May 10, 2020DOI:https://doi.org/10.1016/j.cub.2020.05.023 Summary The unprecedented pandemic of pneumonia caused by a novel coronavirus, SARS-CoV-2, in China and beyond has had major public health impacts on a global scale [1,2]. Although bats are regarded as the most likely natural hosts for SARS-CoV-2 [3], the origins of the virus remain unclear. Here, we report a novel bat-derived coronavirus, denoted RmYN02, identified from a metagenomics analysis of samples from 227 bats collected from Yunnan Province in China between May and October, 2019. Notably, RmYN02 shares 93.3% nucleotide identity with SARS-CoV-2 at the scale of the complete virus genome and 97.2% identity in the 1ab gene, in which it is the closest relative of SARS-CoV-2 reported to date. In contrast, RmYN02 showed low sequence identity (61.3%) to SARS-CoV-2 in the receptor binding domain (RBD) and might not bind to angiotensin-converting enzyme 2 (ACE2). Critically, and in a similar manner to SARS-CoV-2, RmYN02 was characterized by the insertion of multiple amino acids at the junction site of the S1 and S2 subunits of the spike (S) protein. This provides strong evidence that such insertion events can occur naturally in animal betacoronaviruses.
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  • 《5月28日_康奈尔大学等研究SARS-CoV-2刺突蛋白的蛋白水解切割和新型S1 / S2位点的作用》
    • 来源专题：COVID-19科研动态监测
    • 编译者：zhangmin
    • 发布时间：2020-05-31
    • 1.时间：2020年5月28日 2.机构或团队：康奈尔大学、巴黎萨克雷大学 3.事件概要： Cell Press旗下iScience期刊于5月28日发表了康奈尔大学和巴黎萨克雷大学的研究文章“Proteolytic cleavage of the SARS-CoV-2 spike protein and the role of the novel S1/S2 site”。 文章指出，SARS-CoV-2的起源与蝙蝠中的B族β-冠状病毒SARS-CoV和SARS相关的冠状病毒有关。SARS-CoV-2基因组的早期特征表明，刺突（S）蛋白中存在明显的4个氨基酸插入（SPRRAR↓S），位于S1受体结合亚基和S2融合亚基之间的界面处的S1 / S2位点处。文章表示，值得注意的是，该插入片段似乎是SARS相关序列之间的区别特征，并为蛋白酶弗林蛋白酶引入了潜在的切割位点。在该文章中，研究人员利用生化肽裂解测定法测试了一系列可能参与刺突蛋白加工的蛋白酶，即前蛋白转化酶弗林蛋白酶和PC1、胰蛋白酶和II型跨膜丝氨酸蛋白酶（TTSP）、组织蛋白酶B和L，结果发现，弗林蛋白酶可以切割SARS-CoV-2，但不切割SARS-CoV。然而，除了弗林蛋白酶，其他蛋白酶也比SARS-CoV更容易切割SARS-CoV-2。文章表示，获得4个氨基酸的插入片段可将SARS-CoV-2 S1 / S2裂解位点的活化蛋白酶库显着拓宽至已知可能激活冠状病毒S蛋白的所有主要蛋白水解酶类别。研究人员调查了这种新型的S1 / S2裂解位点的潜在作用，并为各种蛋白酶的蛋白水解过程提供了直接的生化证据。研究人员在SARS-CoV-2的起源、病毒稳定性和传播的背景下讨论了这些发现。研究人员还建议，SARS-CoV-2 S1 / S2切割位点可能是由H9流感病毒的突变/重组引起的，而不是由H7和H5 HPAI中发现的更广泛的多碱基位点的聚合酶滑移引起的。术语“多碱基位点”是针对SARS-CoV-2的误称。文章指出，最近发现的与SARS-CoV-2密切相关的蝙蝠冠状病毒（BatCoV-RmYN02）加强了这一概念，该冠状病毒具有扩展的S1 / S2裂解环，缺少其他基本残基（SPAAR↓S）。BatCoV-RmYN02代表了SARS-CoV-2出现的良好候选者，缺乏弗林蛋白酶切割位点并可能利用独特的受体，但提供了SARS-CoV-2天然来源的证据。 文章百世，需要进一步研究以鉴定导致SARS-CoV-2出现的前体序列，并阐明该病毒获得其独特的S1 / S2位点的进化机制。 4.附件： 原文链接：https://www.cell.com/iscience/fulltext/S2589-0042(20)30397-7
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