In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 17, No. 8 ( 2021-8-5), p. e1009772-
Abstract:
Understanding SARS-CoV-2 evolution and host immunity is critical to control COVID-19 pandemics. At the core is an arms-race between SARS-CoV-2 antibody and angiotensin-converting enzyme 2 (ACE2) recognition, a function of the viral protein spike. Mutations in spike impacting antibody and/or ACE2 binding are appearing worldwide, imposing the need to monitor SARS-CoV2 evolution and dynamics in the population. Determining signatures in SARS-CoV-2 that render the virus resistant to neutralizing antibodies is critical. We engineered 25 spike-pseudotyped lentiviruses containing individual and combined mutations in the spike protein, including all defining mutations in the variants of concern, to identify the effect of single and synergic amino acid substitutions in promoting immune escape. We confirmed that E484K evades antibody neutralization elicited by infection or vaccination, a capacity augmented when complemented by K417N and N501Y mutations. In silico analysis provided an explanation for E484K immune evasion. E484 frequently engages in interactions with antibodies but not with ACE2. Importantly, we identified a novel amino acid of concern, S494, which shares a similar pattern. Using the already circulating mutation S494P, we found that it reduces antibody neutralization of convalescent and post-immunization sera, particularly when combined with E484K and with mutations able to increase binding to ACE2, such as N501Y. Our analysis of synergic mutations provides a signature for hotspots for immune evasion and for targets of therapies, vaccines and diagnostics.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1009772
DOI:
10.1371/journal.ppat.1009772.g001
DOI:
10.1371/journal.ppat.1009772.g002
DOI:
10.1371/journal.ppat.1009772.g003
DOI:
10.1371/journal.ppat.1009772.g004
DOI:
10.1371/journal.ppat.1009772.s001
DOI:
10.1371/journal.ppat.1009772.s002
DOI:
10.1371/journal.ppat.1009772.s003
DOI:
10.1371/journal.ppat.1009772.s004
DOI:
10.1371/journal.ppat.1009772.s005
DOI:
10.1371/journal.ppat.1009772.s006
DOI:
10.1371/journal.ppat.1009772.s007
DOI:
10.1371/journal.ppat.1009772.s008
DOI:
10.1371/journal.ppat.1009772.s009
DOI:
10.1371/journal.ppat.1009772.s010
DOI:
10.1371/journal.ppat.1009772.s011
DOI:
10.1371/journal.ppat.1009772.s012
DOI:
10.1371/journal.ppat.1009772.s013
DOI:
10.1371/journal.ppat.1009772.s014
DOI:
10.1371/journal.ppat.1009772.s015
DOI:
10.1371/journal.ppat.1009772.s016
DOI:
10.1371/journal.ppat.1009772.s017
DOI:
10.1371/journal.ppat.1009772.s018
DOI:
10.1371/journal.ppat.1009772.r001
DOI:
10.1371/journal.ppat.1009772.r002
DOI:
10.1371/journal.ppat.1009772.r003
DOI:
10.1371/journal.ppat.1009772.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2205412-1
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