In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 16, No. 12 ( 2020-12-4), p. e1009089-
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.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1009089
DOI:
10.1371/journal.ppat.1009089.g001
DOI:
10.1371/journal.ppat.1009089.g002
DOI:
10.1371/journal.ppat.1009089.g003
DOI:
10.1371/journal.ppat.1009089.g004
DOI:
10.1371/journal.ppat.1009089.g005
DOI:
10.1371/journal.ppat.1009089.s001
DOI:
10.1371/journal.ppat.1009089.s002
DOI:
10.1371/journal.ppat.1009089.s003
DOI:
10.1371/journal.ppat.1009089.s004
DOI:
10.1371/journal.ppat.1009089.s005
DOI:
10.1371/journal.ppat.1009089.s006
DOI:
10.1371/journal.ppat.1009089.s007
DOI:
10.1371/journal.ppat.1009089.s008
DOI:
10.1371/journal.ppat.1009089.s009
DOI:
10.1371/journal.ppat.1009089.s010
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2020
detail.hit.zdb_id:
2205412-1
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