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Prospective mapping of viral mutations that escape antibodies used to treat COVID-19
Science ( IF 44.7 ) Pub Date : 2021-01-25 , DOI: 10.1126/science.abf9302
Tyler N Starr 1 , Allison J Greaney 1, 2, 3 , Amin Addetia 1, 4 , William W Hannon 1, 4 , Manish C Choudhary 5 , Adam S Dingens 1 , Jonathan Z Li 5 , Jesse D Bloom 1, 2, 6
Affiliation  

Antibodies are a potential therapy for SARS-CoV-2, but the risk of the virus evolving to escape them remains unclear. Here we map how all mutations to SARS-CoV-2's receptor-binding domain (RBD) affect binding by the antibodies in the REGN-COV2 cocktail and the antibody LY-CoV016. These complete maps uncover a single amino-acid mutation that fully escapes the REGN-COV2 cocktail, which consists of two antibodies targeting distinct structural epitopes. The maps also identify viral mutations that are selected in a persistently infected patient treated with REGN-COV2, as well as during in vitro viral escape selections. Finally, the maps reveal that mutations escaping the individual antibodies are already present in circulating SARS-CoV-2 strains. Overall, these complete escape maps enable interpretation of the consequences of mutations observed during viral surveillance.

中文翻译:


逃避用于治疗 COVID-19 的抗体的病毒突变的前瞻性图谱



抗体是 SARS-CoV-2 的潜在疗法,但病毒进化以逃避抗体的风险仍不清楚。在这里,我们绘制了 SARS-CoV-2 受体结合域 (RBD) 的所有突变如何影响 REGN-COV2 混合物中的抗体和抗体 LY-CoV016 的结合。这些完整的图谱揭示了一个完全逃脱 REGN-COV2 混合物的单个氨基酸突变,该混合物由两种针对不同结构表位的抗体组成。这些图谱还识别了在接受 REGN-COV2 治疗的持续感染患者以及体外病毒逃逸选择过程中选择的病毒突变。最后,这些图谱显示,逃避单个抗体的突变已经存在于循环的 SARS-CoV-2 毒株中。总的来说,这些完整的逃逸图能够解释病毒监测期间观察到的突变的后果。
更新日期:2021-01-25
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