| Literature DB >> 33473140 |
Zhiqiang Ku1, Xuping Xie2, Edgar Davidson3, Xiaohua Ye1, Hang Su1, Vineet D Menachery4, Yize Li5, Zihao Yuan1, Xianwen Zhang2, Antonio E Muruato2, Ariadna Grinyo I Escuer3, Breanna Tyrell3, Kyle Doolan3, Benjamin J Doranz3, Daniel Wrapp6, Paul F Bates5, Jason S McLellan6, Susan R Weiss5, Ningyan Zhang7, Pei-Yong Shi8, Zhiqiang An9.
Abstract
Antibody cocktails represent a promising approach to prevent SARS-CoV-2 escape. The determinants for selecting antibody combinations and the mechanism that antibody cocktails prevent viral escape remain unclear. We compared the critical residues in the receptor-binding domain (RBD) used by multiple neutralizing antibodies and cocktails and identified a combination of two antibodies CoV2-06 and CoV2-14 for preventing viral escape. The two antibodies simultaneously bind to non-overlapping epitopes and independently compete for receptor binding. SARS-CoV-2 rapidly escapes from individual antibodies by generating resistant mutations in vitro, but it doesn't escape from the cocktail due to stronger mutational constraints on RBD-ACE2 interaction and RBD protein folding requirements. We also identified a conserved neutralizing epitope shared between SARS-CoV-2 and SARS-CoV for antibody CoV2-12. Treatments with CoV2-06 and CoV2-14 individually and in combination confer protection in mice. These findings provide insights for rational selection and mechanistic understanding of antibody cocktails as candidates for treating COVID-19.Entities:
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Year: 2021 PMID： 33473140 PMCID： PMC7817669 DOI： 10.1038/s41467-020-20789-7
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919