The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic continues, with devasting consequences for human lives and the global economy 1 , 2 . The discovery and development of virus-neutralizing monoclonal antibodies could be one approach to treat or prevent infection by this coronavirus. Here we report the isolation of sixty-one SARS-CoV-2-neutralizing monoclonal antibodies from five patients infected with SARS-CoV-2 and admitted to hospital with severe coronavirus disease 2019 (COVID-19). Among these are nineteen antibodies that potently neutralized authentic SARS-CoV-2 in vitro, nine of which exhibited very high potency, with 50% virus-inhibitory concentrations of 0.7 to 9 ng ml −1 . Epitope mapping showed that this collection of nineteen antibodies was about equally divided between those directed against the receptor-binding domain (RBD) and those directed against the N-terminal domain (NTD), indicating that both of these regions at the top of the viral spike are immunogenic. In addition, two other powerful neutralizing antibodies recognized quaternary epitopes that overlap with the domains at the top of the spike. Cryo-electron microscopy reconstructions of one antibody that targets the RBD, a second that targets the NTD, and a third that bridges two separate RBDs showed that the antibodies recognize the closed, ‘all RBD-down’ conformation of the spike. Several of these monoclonal antibodies are promising candidates for clinical development as potential therapeutic and/or prophylactic agents against SARS-CoV-2. A diverse collection of potent neutralizing antibodies against the SARS-CoV-2 spike protein have been isolated from five patients with severe COVID-19 and high serum neutralization titres.

中文翻译：

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针对 SARS-CoV-2 尖峰上多个表位的强效中和抗体

严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 大流行仍在继续，对人类生活和全球经济造成毁灭性后果 1 、 2 。病毒中和单克隆抗体的发现和开发可能是治疗或预防这种冠状病毒感染的一种方法。在这里，我们报告了从 5 名感染 SARS-CoV-2 并因 2019 年严重冠状病毒病 (COVID-19) 入院的患者中分离出的 61 种 SARS-CoV-2 中和单克隆抗体。其中有 19 种抗体可在体外有效中和真正的 SARS-CoV-2，其中 9 种表现出非常高的效力，50% 的病毒抑制浓度为 0.7 至 9 ng ml -1 。表位作图显示，这 19 种抗体的集合大致相等地分为针对受体结合域 (RBD) 的抗体和针对 N 端结构域 (NTD) 的抗体，表明这两个区域都位于病毒的顶部穗是免疫原性的。此外，另外两种强大的中和抗体识别了与尖峰顶部结构域重叠的四级表位。一种针对 RBD 的抗体、第二种针对 NTD 的抗体和第三种连接两个独立 RBD 的抗体的冷冻电子显微镜重建表明，这些抗体识别出封闭的、“全 RBD 向下”的尖峰构象。这些单克隆抗体中的一些是临床开发的有希望的候选者，作为针对 SARS-CoV-2 的潜在治疗和/或预防剂。