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.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Ku Z,Xie X,Davidson E,Ye X,Su H,Menachery VD,Li Y,Yuan Z,Zhang X,Muruato AE,I Escuer AG,Tyrell B,Doolan K,Doranz BJ,Wrapp D,Bates PF,McLellan JS,Weiss SR,Zhang N,Shi PY,An Zdoi
10.1038/s41467-020-20789-7subject
Has Abstractpub_date
2021-01-20 00:00:00pages
469issue
1issn
2041-1723pii
10.1038/s41467-020-20789-7journal_volume
12pub_type
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