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HERO ID
8786181
Reference Type
Journal Article
Title
Signatures in SARS-CoV-2 spike protein conferring escape to neutralizing antibodies
Author(s)
Alenquer, M; Ferreira, F; Lousa, D; Valério, M; Medina-Lopes, M; Bergman, ML; Gonçalves, J; Demengeot, J; Leite, RB; Lilue, J; Ning, Z; Penha-Gonçalves, C; Soares, H; Soares, CM; Amorim, MJ
Year
2021
Is Peer Reviewed?
1
Journal
P L o S Pathogens
ISSN:
1553-7366
Volume
17
Issue
8
Page Numbers
e1009772
Language
English
PMID
34352039
DOI
10.1371/journal.ppat.1009772
Web of Science Id
WOS:000685263100002
URL
http://WOS:000685263100002
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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.
Keywords
RECEPTOR-BINDING DOMAIN; PARTICLE MESH EWALD; MOLECULAR-DYNAMICS; MUTATIONS; ACE2; EVOLUTIONARY; INFECTION; COVID-19
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