In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 19, No. 5 ( 2023-5-1), p. e1011308-
Abstract:
The global spread of the SARS-CoV-2 virus has resulted in emergence of lineages which impact the effectiveness of immunotherapies and vaccines that are based on the early Wuhan isolate. All currently approved vaccines employ the spike protein S, as it is the target for neutralizing antibodies. Here we describe two SARS-CoV-2 isolates with unusually large deletions in the N-terminal domain (NTD) of the spike. Cryo-EM structural analysis shows that the deletions result in complete reshaping of the NTD supersite, an antigenically important region of the NTD. For both spike variants the remodeling of the NTD negatively affects binding of all tested NTD-specific antibodies in and outside of the NTD supersite. For one of the variants, we observed a P9L mediated shift of the signal peptide cleavage site resulting in the loss of a disulfide-bridge; a unique escape mechanism with high antigenic impact. Although the observed deletions and disulfide mutations are rare, similar modifications have become independently established in several other lineages, indicating a possibility to become more dominant in the future. The observed plasticity of the NTD foreshadows its broad potential for immune escape with the continued spread of SARS-CoV-2.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1011308
DOI:
10.1371/journal.ppat.1011308.g001
DOI:
10.1371/journal.ppat.1011308.g002
DOI:
10.1371/journal.ppat.1011308.g003
DOI:
10.1371/journal.ppat.1011308.g004
DOI:
10.1371/journal.ppat.1011308.g005
DOI:
10.1371/journal.ppat.1011308.g006
DOI:
10.1371/journal.ppat.1011308.s001
DOI:
10.1371/journal.ppat.1011308.s002
DOI:
10.1371/journal.ppat.1011308.s003
DOI:
10.1371/journal.ppat.1011308.s004
DOI:
10.1371/journal.ppat.1011308.s005
DOI:
10.1371/journal.ppat.1011308.s006
DOI:
10.1371/journal.ppat.1011308.s007
DOI:
10.1371/journal.ppat.1011308.s008
DOI:
10.1371/journal.ppat.1011308.s009
DOI:
10.1371/journal.ppat.1011308.s010
DOI:
10.1371/journal.ppat.1011308.s011
DOI:
10.1371/journal.ppat.1011308.s012
DOI:
10.1371/journal.ppat.1011308.s013
DOI:
10.1371/journal.ppat.1011308.s014
DOI:
10.1371/journal.ppat.1011308.s015
DOI:
10.1371/journal.ppat.1011308.s016
DOI:
10.1371/journal.ppat.1011308.r001
DOI:
10.1371/journal.ppat.1011308.r002
DOI:
10.1371/journal.ppat.1011308.r003
DOI:
10.1371/journal.ppat.1011308.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2205412-1
Bookmarklink