A strong cocktail against SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is initiated by the trimeric spike protein that decorates the virus and binds the ACE2 receptor. Antibodies against the spike that neutralize viral infection have potential as therapeutics. Tortorici et al. describe two very potent antibodies, S2E12 and S2M11. Electron microscopy structures characterized the binding and showed that S2E12 traps the spike in a conformation that cannot bind ACE2. Both antibodies protected hamsters against SARS-CoV-2 challenge and may be useful in antibody cocktails to combat the virus and prevent the development of resistance. Science, this issue p. 950 A potent antibody cocktail blocks attachment of SARS-CoV-2 to the host receptor and activates a protective immune response. Efficient therapeutic options are needed to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has caused more than 922,000 fatalities as of 13 September 2020. We report the isolation and characterization of two ultrapotent SARS-CoV-2 human neutralizing antibodies (S2E12 and S2M11) that protect hamsters against SARS-CoV-2 challenge. Cryo–electron microscopy structures show that S2E12 and S2M11 competitively block angiotensin-converting enzyme 2 (ACE2) attachment and that S2M11 also locks the spike in a closed conformation by recognition of a quaternary epitope spanning two adjacent receptor-binding domains. Antibody cocktails that include S2M11, S2E12, or the previously identified S309 antibody broadly neutralize a panel of circulating SARS-CoV-2 isolates and activate effector functions. Our results pave the way to implement antibody cocktails for prophylaxis or therapy, circumventing or limiting the emergence of viral escape mutants.

中文翻译：

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超强人类抗体通过多种机制抵御 SARS-CoV-2 攻击

针对 SARS-CoV-2 严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 感染的强效混合物是由修饰病毒并结合 ACE2 受体的三聚刺突蛋白启动的。中和病毒感染的针对尖峰的抗体具有作为治疗药物的潜力。托托里奇等人。描述了两种非常有效的抗体：S2E12 和 S2M11。电子显微镜结构表征了这种结合，并表明 S2E12 将刺突捕获在无法结合 ACE2 的构象中。这两种抗体都能保护仓鼠免受 SARS-CoV-2 的攻击，并且可能可用于抗体混合物中来对抗病毒并防止耐药性的产生。科学，本期第 14 页。950 一种有效的抗体混合物可阻止 SARS-CoV-2 与宿主受体的附着并激活保护性免疫反应。需要有效的治疗方案来控制严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的传播，截至 2020 年 9 月 13 日，该病毒已导致超过 922,000 人死亡。我们报告了两种超强 SARS-CoV-2 的分离和表征人类中和抗体（S2E12 和 S2M11）可保护仓鼠免受 SARS-CoV-2 的攻击。冷冻电子显微镜结构显示，S2E12 和 S2M11 竞争性阻断血管紧张素转换酶 2 (ACE2) 附着，并且 S2M11 还通过识别跨越两个相邻受体结合域的四级表位，将刺突锁定在闭合构象中。包含 S2M11、S2E12 或先前鉴定的 S309 抗体的抗体混合物可广泛中和一组循环的 SARS-CoV-2 分离株并激活效应器功能。我们的结果为实施抗体鸡尾酒预防或治疗、规避或限制病毒逃逸突变体的出现铺平了道路。