Many studies have examined the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on neutralizing antibody activity after they have become dominant strains. Here, we evaluate the consequences of further viral evolution. We demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, as opposed to the one to three found in previously studied variants of concern, are more resistant to neutralization by therapeutic antibodies and serum from vaccine recipients. We identify an antibody that binds the RBD core to neutralize pseudotypes for all tested variants but show that the RBD can acquire an N-linked glycan to escape neutralization. Our findings portend continued emergence of escape variants as SARS-CoV-2 adapts to humans.

中文翻译：

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SARS-CoV-2受体结合域持续逃避抗体的结构基础

许多研究探讨了严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 变种成为优势毒株后对中和抗体活性的影响。在这里，我们评估病毒进一步进化的后果。我们证明了 SARS-CoV-2 受体结合域 (RBD) 可以耐受大量同时发生的抗体逃逸突变的机制，并表明假型包含多达 7 个突变，而不是先前研究的相关变体中发现的 1 到 3 个突变，对治疗性抗体和疫苗接受者血清的中和作用具有更强的抵抗力。我们鉴定了一种结合 RBD 核心以中和所有测试变体的假型的抗体，但表明 RBD 可以获得 N 连接聚糖来逃避中和。我们的发现预示着随着 SARS-CoV-2 适应人类，逃逸变异将继续出现。