Severe acute respiratory syndrome coronaviruses 1 (SARS-CoV) and 2 (SARS-CoV-2), including SARS-CoV-2 variants of concern, can cause deadly infections. The mortality associated with sarbecovirus infection underscores the importance of developing broadly effective countermeasures against them, which could be key in the prevention and mitigation of current and future zoonotic events. Here, we demonstrate the neutralization of SARS-CoV; bat coronaviruses WIV-1 and RsSHC014; and SARS-CoV-2 variants D614G, B.1.1.7, B.1.351, P.1, B.1.429, B.1.526, B.1.617.1, and B.1.617.2 by a receptor binding domain (RBD)–specific human antibody, DH1047. Prophylactic and therapeutic treatment with DH1047 was protective against SARS-CoV, WIV-1, RsSHC014, and SARS-CoV-2 B.1.351 infection in mice. Binding and structural analysis showed high affinity binding of DH1047 to an epitope that is highly conserved among sarbecoviruses. Thus, DH1047 is a broadly protective antibody that can prevent infection and mitigate outbreaks caused by SARS-related strains and SARS-CoV-2 variants. Our results also suggest that the conserved RBD epitope bound by DH1047 is a rational target for a universal sarbecovirus vaccine.

中文翻译：

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一种广泛交叉反应的抗体可中和并防止小鼠受到 sarbecovirus 攻击

严重急性呼吸系统综合症冠状病毒 1 (SARS-CoV) 和 2 (SARS-CoV-2)，包括令人担忧的 SARS-CoV-2 变体，可导致致命感染。与 sarbecovirus 感染相关的死亡率凸显了针对它们制定广泛有效的对策的重要性，这可能是预防和减轻当前和未来人畜共患病事件的关键。在这里，我们展示了 SARS-CoV 的中和作用；蝙蝠冠状病毒 WIV-1 和 RsSHC014；和 SARS-CoV-2 变体 D614G、B.1.1.7、B.1.351、P.1、B.1.429、B.1.526、B.1.617.1 和 B.1.617.2 通过受体结合域（RBD )–特异性人类抗体，DH1047。用 DH1047 进行预防和治疗可防止小鼠感染 SARS-CoV、WIV-1、RsSHC014 和 SARS-CoV-2 B.1.351。结合和结构分析显示 DH1047 与在 sarbecoviruses 中高度保守的表位具有高亲和力结合。因此，DH1047 是一种广泛的保护性抗体，可以预防感染并减轻由 SARS 相关毒株和 SARS-CoV-2 变体引起的爆发。我们的结果还表明，由 DH1047 结合的保守 RBD 表位是通用 sarbecovirus 疫苗的合理目标。