A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike.
Cell
; 186(6): 1263-1278.e20, 2023 03 16.
Article
in English
| MEDLINE | ID: covidwho-2229215
ABSTRACT
A major challenge in understanding SARS-CoV-2 evolution is interpreting the antigenic and functional effects of emerging mutations in the viral spike protein. Here, we describe a deep mutational scanning platform based on non-replicative pseudotyped lentiviruses that directly quantifies how large numbers of spike mutations impact antibody neutralization and pseudovirus infection. We apply this platform to produce libraries of the Omicron BA.1 and Delta spikes. These libraries each contain â¼7,000 distinct amino acid mutations in the context of up to â¼135,000 unique mutation combinations. We use these libraries to map escape mutations from neutralizing antibodies targeting the receptor-binding domain, N-terminal domain, and S2 subunit of spike. Overall, this work establishes a high-throughput and safe approach to measure how â¼105 combinations of mutations affect antibody neutralization and spike-mediated infection. Notably, the platform described here can be extended to the entry proteins of many other viruses.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
RNA Viruses
/
COVID-19
Topics:
Variants
Limits:
Humans
Language:
English
Journal:
Cell
Year:
2023
Document Type:
Article
Affiliation country:
J.cell.2023.02.001
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