Most antibodies isolated from COVID-19 patients are specific to SARS-CoV-2. COVA1-16 is a relatively rare antibody that also cross-neutralizes SARS-CoV. Here we determined a crystal structure of COVA1-16 Fab with the SARS-CoV-2 RBD, and a negative-stain EM reconstruction with the spike glycoprotein trimer, to elucidate the structural basis of its cross-reactivity. COVA1-16 binds a highly conserved epitope on the SARS-CoV-2 RBD, mainly through a long CDR H3, and competes with ACE2 binding due to steric hindrance rather than epitope overlap. COVA1-16 binds to a flexible up conformation of the RBD on the spike and relies on antibody avidity for neutralization. These findings, along with structural and functional rationale for the epitope conservation, provide a blueprint for development of more universal SARS-like coronavirus vaccines and therapies.

中文翻译：

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SARS-CoV-2抗体与功能保守位点的交叉中和是通过亲和力介导的。

从COVID-19患者中分离出的大多数抗体对SARS-CoV-2具有特异性。COVA1-16是一种相对罕见的抗体，也可以交叉中和SARS-CoV。在这里，我们确定了具有SARS-CoV-2 RBD的COVA1-16 Fab的晶体结构，以及带有尖峰糖蛋白三聚体的负染色EM重建，以阐明其交叉反应的结构基础。COVA1-16主要通过长CDR H3结合SARS-CoV-2 RBD上高度保守的表位，并由于空间位阻而不是表位重叠而与ACE2竞争。COVA1-16结合到尖峰上RBD的柔性向上构象，并依赖于抗体亲和力进行中和。这些发现，以及表位保护的结构和功能原理，为开发更通用的SARS样冠状病毒疫苗和疗法提供了蓝图。