Many neutralizing antibodies (nAbs) elicited to ancestral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through natural infection and vaccination have reduced effectiveness to SARS-CoV-2 variants. Here, we show that therapeutic antibody ADG20 is able to neutralize SARS-CoV-2 variants of concern (VOCs) including Omicron (B.1.1.529) as well as other SARS-related coronaviruses. We delineate the structural basis of this relatively escape-resistant epitope that extends from one end of the receptor binding site (RBS) into the highly conserved CR3022 site. ADG20 can then benefit from high potency through direct competition with ACE2 in the more variable RBS and interaction with the more highly conserved CR3022 site. Importantly, antibodies that are able to target this site generally neutralize a broad range of VOCs, albeit with reduced potency against Omicron. Thus, this conserved and vulnerable site can be exploited for the design of universal vaccines and therapeutic antibodies.

中文翻译：

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SARS 相关冠状病毒中广泛而有效的中和表位


许多通过自然感染和疫苗接种引起的针对祖先严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的中和抗体 (nAb) 降低了对 SARS-CoV-2 变种的有效性。在这里，我们证明治疗性抗体 ADG20 能够中和 SARS-CoV-2 相关变体 (VOC)，包括 Omicron (B.1.1.529) 以及其他 SARS 相关冠状病毒。我们描述了这种相对难以逃逸的表位的结构基础，该表位从受体结合位点（RBS）的一端延伸到高度保守的 CR3022 位点。然后，ADG20 可以通过与变异性更大的 RBS 中的 ACE2 直接竞争以及与更高度保守的 CR3022 位点相互作用，从而获得高效能。重要的是，能够靶向该位点的抗体通常可以中和多种 VOC，尽管针对 Omicron 的效力有所降低。因此，这个保守且脆弱的位点可用于设计通用疫苗和治疗抗体。