A natural mutation between SARS-CoV-2 and SARS-CoV determines neutralization by a cross-reactive antibody.
PLoS Pathog
; 16(12): e1009089, 2020 12.
Article
in English
| MEDLINE | ID: covidwho-961466
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
ABSTRACT
Epitopes that are conserved among SARS-like coronaviruses are attractive targets for design of cross-reactive vaccines and therapeutics. CR3022 is a SARS-CoV neutralizing antibody to a highly conserved epitope on the receptor binding domain (RBD) on the spike protein that is able to cross-react with SARS-CoV-2, but with lower affinity. Using x-ray crystallography, mutagenesis, and binding experiments, we illustrate that of four amino acid differences in the CR3022 epitope between SARS-CoV-2 and SARS-CoV, a single mutation P384A fully determines the affinity difference. CR3022 does not neutralize SARS-CoV-2, but the increased affinity to SARS-CoV-2 P384A mutant now enables neutralization with a similar potency to SARS-CoV. We further investigated CR3022 interaction with the SARS-CoV spike protein by negative-stain EM and cryo-EM. Three CR3022 Fabs bind per trimer with the RBD observed in different up-conformations due to considerable flexibility of the RBD. In one of these conformations, quaternary interactions are made by CR3022 to the N-terminal domain (NTD) of an adjacent subunit. Overall, this study provides insights into antigenic variation and potential cross-neutralizing epitopes on SARS-like viruses.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Severe Acute Respiratory Syndrome
/
Severe acute respiratory syndrome-related coronavirus
/
Antibodies, Neutralizing
/
SARS-CoV-2
/
COVID-19
/
Antibodies, Viral
Type of study:
Randomized controlled trials
Topics:
Vaccines
Limits:
Humans
Language:
English
Journal:
PLoS Pathog
Year:
2020
Document Type:
Article
Affiliation country:
Journal.ppat.1009089
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