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TitleComplete Mapping of Mutations to the SARS-CoV-2 Spike Receptor-Binding Domain that Escape Antibody Recognition.
Journal, issue, pagesCell Host Microbe, Vol. 29, Issue 1, Page 44-57.e9, Year 2021
Publish dateJan 13, 2021
AuthorsAllison J Greaney / Tyler N Starr / Pavlo Gilchuk / Seth J Zost / Elad Binshtein / Andrea N Loes / Sarah K Hilton / John Huddleston / Rachel Eguia / Katharine H D Crawford / Adam S Dingens / Rachel S Nargi / Rachel E Sutton / Naveenchandra Suryadevara / Paul W Rothlauf / Zhuoming Liu / Sean P J Whelan / Robert H Carnahan / James E Crowe / Jesse D Bloom /
PubMed AbstractAntibodies targeting the SARS-CoV-2 spike receptor-binding domain (RBD) are being developed as therapeutics and are a major contributor to neutralizing antibody responses elicited by infection. Here, ...Antibodies targeting the SARS-CoV-2 spike receptor-binding domain (RBD) are being developed as therapeutics and are a major contributor to neutralizing antibody responses elicited by infection. Here, we describe a deep mutational scanning method to map how all amino-acid mutations in the RBD affect antibody binding and apply this method to 10 human monoclonal antibodies. The escape mutations cluster on several surfaces of the RBD that broadly correspond to structurally defined antibody epitopes. However, even antibodies targeting the same surface often have distinct escape mutations. The complete escape maps predict which mutations are selected during viral growth in the presence of single antibodies. They further enable the design of escape-resistant antibody cocktails-including cocktails of antibodies that compete for binding to the same RBD surface but have different escape mutations. Therefore, complete escape-mutation maps enable rational design of antibody therapeutics and assessment of the antigenic consequences of viral evolution.
External linksCell Host Microbe / PubMed:33259788 / PubMed Central
MethodsEM (single particle)
Resolution25.0 - 28.0 Å
Structure data

EMDB-22148:
Negative stain EM map of SARS-COV-2 spike protein open RBD (trimer) with Fab COV2-2096
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-22149:
Negative stain EM map of SARS-COV-2 spike protein (trimer) with Fab COV2-2832
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-22627:
Negative stain EM map of SARS-COV-2 spike protein (trimer) with Fab COV2-2082
Method: EM (single particle) / Resolution: 28.0 Å

EMDB-22628:
Negative stain EM map of SARS-COV-2 spike protein (trimer) with Fab COV2-2479
Method: EM (single particle) / Resolution: 25.0 Å

Source
  • Severe acute respiratory syndrome coronavirus 2
  • Homo sapiens (human)

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