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Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody

机译：通过人单克隆SARS-COV抗体的SARS-COV-2交叉中和

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摘要

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly emerged coronavirus that is responsible for the current pandemic of coronavirus disease 2019 (COVID-19), which has resulted in more than 3.7 million infections and 260,000 deaths as of 6 May 2020 12 . Vaccine and therapeutic discovery efforts are paramount to curb the pandemic spread of this zoonotic virus. The SARS-CoV-2 spike (S) glycoprotein promotes entry into host cells and is the main target of neutralizing antibodies. Here we describe several monoclonal antibodies that target the Sglycoprotein of SARS-CoV-2, which we identified from memory B cells of an individual who was infected with severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003. One antibody (named S309) potently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2, by engaging the receptor-binding domain of the S glycoprotein. Using cryo-electron microscopy and binding assays, we show that S309 recognizes an epitope containing a glycan that is conserved within the Sarbecovirus subgenus, without competing with receptor attachment. Antibody cocktails that include S309 in combination with other antibodiesthat we identified further enhanced SARS-CoV-2 neutralization, and may limit the emergence of neutralization-escape mutants. These results pave the way for using S309 and antibody cocktails containing S309 for prophylaxis in individuals at a high risk of exposure or as a post-exposure therapy to limit or treat severe disease.
机译：严重的急性呼吸综合征冠状病毒2（SARS-COV-2）是一种新出现的冠状病毒，该冠状病毒是对2019年（Covid-19）的目前的冠状病毒疾病大会，这导致了超过370万的感染和260,000人死亡6 5月2020年12月12日。疫苗和治疗性的发现努力是抑制这种动物园病毒的大流行蔓延。 SARS-COV-2穗糖蛋白促进进入宿主细胞，是中和抗体的主要靶标。在这里，我们描述了靶向SARS-COV-2的甘蔗糖蛋白的几种单克隆抗体，我们从2003年感染严重急性呼吸综合征冠状病毒（SARS-COV）的个体内存中鉴定的。一抗（名为S309）通过接合S糖蛋白的受体结合结构域来易于中和SARS-COV-2和SARS-COV伪病毒以及真实的SARS-COV-2。使用低温电子显微镜和结合测定，我们表明S309识别出含有在Sarbecovirus亚因子内保守的甘草的表位，而不与受体附着竞争。包括S309与其他抗体组合的抗体鸡尾酒我们鉴定了进一步增强的SARS-COV-2中和，并且可能限制中和逃逸突变体的出现。这些结果铺平了使用S309和含有S309的抗体鸡尾酒的方法，以在暴露的高风险或作为暴露后疗法以限制或治疗严重疾病的情况下的个体中的预防。

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  • 来源
    《Nature》 |2020年第7815期|290-295|共6页
  • 作者

    Pinto Dora; Park Young-Jun; Beltramello Martina; Walls Alexandra C.; Tortorici M. Alejandra; Bianchi Siro; Jaconi Stefano; Culap Katja; Zatta Fabrizia; De Marco Anna; Peter Alessia; Guarino Barbara; Spreafico Roberto; Cameroni Elisabetta; Case James Brett; Chen Rita E.; Havenar-Daughton Colin; Snell Gyorgy; Telenti Amalio; Virgin Herbert W.; Lanzavecchia Antonio; Diamond Michael S.; Fink Katja; Veesler David; Corti Davide;

  • 作者单位

    Humabs BioMed SA Vir Biotechnol Bellinzona Switzerland;

    Univ Washington Dept Biochem Seattle WA 98195 USA;

    Humabs BioMed SA Vir Biotechnol Bellinzona Switzerland;

    Univ Washington Dept Biochem Seattle WA 98195 USA;

    Univ Washington Dept Biochem Seattle WA 98195 USA|Inst Pasteur Paris France|CNRS UMR 3569 Unite Virol Struct Paris France;

    Humabs BioMed SA Vir Biotechnol Bellinzona Switzerland;

    Humabs BioMed SA Vir Biotechnol Bellinzona Switzerland;

    Humabs BioMed SA Vir Biotechnol Bellinzona Switzerland;

    Humabs BioMed SA Vir Biotechnol Bellinzona Switzerland;

    Humabs BioMed SA Vir Biotechnol Bellinzona Switzerland;

    Humabs BioMed SA Vir Biotechnol Bellinzona Switzerland;

    Humabs BioMed SA Vir Biotechnol Bellinzona Switzerland;

    Vir Biotechnol San Francisco CA USA;

    Humabs BioMed SA Vir Biotechnol Bellinzona Switzerland;

    Washington Univ Sch Med Dept Med St Louis MO 63110 USA;

    Washington Univ Sch Med Dept Med St Louis MO 63110 USA|Washington Univ Sch Med Dept Pathol & Immunol St Louis MO USA;

    Vir Biotechnol San Francisco CA USA;

    Vir Biotechnol San Francisco CA USA;

    Vir Biotechnol San Francisco CA USA;

    Vir Biotechnol San Francisco CA USA;

    Humabs BioMed SA Vir Biotechnol Bellinzona Switzerland|Univ Svizzera Italiana Inst Res Biomed Bellinzona Switzerland;

    Washington Univ Sch Med Dept Med St Louis MO 63110 USA|Washington Univ Sch Med Dept Pathol & Immunol St Louis MO USA|Washington Univ Sch Med Dept Mol Microbiol St Louis MO 63110 USA;

    Humabs BioMed SA Vir Biotechnol Bellinzona Switzerland;

    Univ Washington Dept Biochem Seattle WA 98195 USA;

    Humabs BioMed SA Vir Biotechnol Bellinzona Switzerland;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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