Molecular insights into receptor binding energetics and neutralization of SARS-CoV-2 variants.
Angiotensin-Converting Enzyme 2
/ chemistry
Antibodies, Neutralizing
/ immunology
COVID-19
/ therapy
Humans
Kinetics
Microscopy, Atomic Force
Molecular Dynamics Simulation
Mutation
Protein Binding
/ drug effects
Protein Interaction Domains and Motifs
Protein Stability
SARS-CoV-2
/ genetics
Spike Glycoprotein, Coronavirus
/ genetics
Thermodynamics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
30 11 2021
30 11 2021
Historique:
received:
06
08
2021
accepted:
15
11
2021
entrez:
1
12
2021
pubmed:
2
12
2021
medline:
15
12
2021
Statut:
epublish
Résumé
Despite an unprecedented global gain in knowledge since the emergence of SARS-CoV-2, almost all mechanistic knowledge related to the molecular and cellular details of viral replication, pathology and virulence has been generated using early prototypic isolates of SARS-CoV-2. Here, using atomic force microscopy and molecular dynamics, we investigated how these mutations quantitatively affected the kinetic, thermodynamic and structural properties of RBD-ACE2 complex formation. We observed for several variants of concern a significant increase in the RBD-ACE2 complex stability. While the N501Y and E484Q mutations are particularly important for the greater stability, the N501Y mutation is unlikely to significantly affect antibody neutralization. This work provides unprecedented atomistic detail on the binding of SARS-CoV-2 variants and provides insight into the impact of viral mutations on infection-induced immunity.
Identifiants
pubmed: 34848718
doi: 10.1038/s41467-021-27325-1
pii: 10.1038/s41467-021-27325-1
pmc: PMC8633007
doi:
Substances chimiques
Antibodies, Neutralizing
0
Spike Glycoprotein, Coronavirus
0
spike protein, SARS-CoV-2
0
ACE2 protein, human
EC 3.4.17.23
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6977Subventions
Organisme : EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)
ID : 758224
Organisme : Fonds De La Recherche Scientifique - FNRS (Belgian National Fund for Scientific Research)
ID : CR-2019S-01
Informations de copyright
© 2021. The Author(s).
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