RT Journal Article
SR Electronic
T1 Amino acids 484 and 494 of SARS-CoV-2 spike are hotspots of immune evasion affecting antibody but not ACE2 binding
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.04.22.441007
DO 10.1101/2021.04.22.441007
A1 Marta Alenquer
A1 Filipe Ferreira
A1 Diana Lousa
A1 Mariana Valério
A1 Mónica Medina-Lopes
A1 Marie-Louise Bergman
A1 Juliana Gonçalves
A1 Jocelyne Demengeot
A1 Ricardo B. Leite
A1 Jingtao Lilue
A1 Zemin Ning
A1 Carlos Penha-Gonçalves
A1 Helena Soares
A1 Cláudio M. Soares
A1 Maria João Amorim
YR 2021
UL http://biorxiv.org/content/early/2021/05/14/2021.04.22.441007.abstract
AB 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, with the effect of mutation synergy still incompletely understood. We engineered 25 spike-pseudotyped lentiviruses containing individual and combined mutations, and 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 N501Y. Our analysis of synergic mutations provides a landscape for hotspots for immune evasion and for targets for therapies, vaccines and diagnostics.One-Sentence Summary Amino acids in SARS-CoV-2 spike protein implicated in immune evasion are biased for binding to neutralizing antibodies but dispensable for binding the host receptor angiotensin-converting enzymeCompeting Interest StatementThe authors have declared no competing interest.