A tethered ligand assay to probe SARS-CoV-2:ACE2 interactions.
AFM
SARS-CoV-2
force spectroscopy
host–pathogen interactions
magnetic tweezers
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
05 04 2022
05 04 2022
Historique:
entrez:
21
3
2022
pubmed:
22
3
2022
medline:
2
4
2022
Statut:
ppublish
Résumé
SignificanceIn the dynamic environment of the airways, where SARS-CoV-2 infections are initiated by binding to human host receptor ACE2, mechanical stability of the viral attachment is a crucial fitness advantage. Using single-molecule force spectroscopy techniques, we mimic the effect of coughing and sneezing, thereby testing the force stability of SARS-CoV-2 RBD:ACE2 interaction under physiological conditions. Our results reveal a higher force stability of SARS-CoV-2 binding to ACE2 compared to SARS-CoV-1, causing a possible fitness advantage. Our assay is sensitive to blocking agents preventing RBD:ACE2 bond formation. It will thus provide a powerful approach to investigate the modes of action of neutralizing antibodies and other agents designed to block RBD binding to ACE2 that are currently developed as potential COVID-19 therapeutics.
Identifiants
pubmed: 35312342
doi: 10.1073/pnas.2114397119
pmc: PMC9168514
doi:
Substances chimiques
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
e2114397119Subventions
Organisme : Deutsche Forschungsgemeinschaft (DFG)
ID : 386143268
Organisme : Deutsche Forschungsgemeinschaft (DFG)
ID : 111166240
Organisme : European Molecular Biology Organization (EMBO)
ID : ALTF 1047-2019
Organisme : Auburn University (AU)
Organisme : Spanish Ministry of Science, Innovation and Universities for the Spanish State Research Agency Retos Grant
ID : RTI2018-099318-B-I00
Organisme : Cofunded by the European Regional Development Fund (FEDER)
Organisme : Physics Department of the LMU Munich
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