A tethered ligand assay to probe SARS-CoV-2:ACE2 interactions-Reference-Cited by-同舟云学术

A tethered ligand assay to probe SARS-CoV-2:ACE2 interactions

Published:2022-03-21 Issue:14 Volume:119 Page:
ISSN:0027-8424
Container-title:Proceedings of the National Academy of Sciences
language:en
Short-container-title:Proc. Natl. Acad. Sci. U.S.A.

Author:

Bauer Magnus S.¹²³^ORCID,Gruber Sophia¹²,Hausch Adina¹²,Gomes Priscila S. F. C.⁴^ORCID,Milles Lukas F.⁵⁶^ORCID,Nicolaus Thomas¹²,Schendel Leonard C.¹²^ORCID,Navajas Pilar López⁷,Procko Erik⁸⁹^ORCID,Lietha Daniel⁷^ORCID,Melo Marcelo C. R.⁴^ORCID,Bernardi Rafael C.⁴^ORCID,Gaub Hermann E.¹²^ORCID,Lipfert Jan¹²^ORCID

Affiliation:

1. Department of Physics, LMU Munich, 80799 Munich, Germany

2. Center for NanoScience, LMU Munich, 80799 Munich, Germany

3. Department of Chemical Engineering, Stanford University, Stanford, CA 94305

4. Department of Physics, Auburn University, Auburn, AL 36849

5. Department of Biochemistry, University of Washington, Seattle, WA 98195

6. Institute for Protein Design, University of Washington, Seattle, WA 98195

7. Centro de Investigaciones Biológicas Margarita Salas, Spanish National Research Council, 28040 Madrid, Spain

8. Department of Biochemistry, University of Illinois, Urbana, IL 61801

9. Cancer Center at Illinois, University of Illinois, Urbana, IL 61801

Abstract

Significance In 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.

Funder

Deutsche Forschungsgemeinschaft

European Molecular Biology Organization

Auburn University

Spanish Ministry of Science, Innovation and Universities for the Spanish State Research Agency Retos Grant

Cofunded by the European Regional Development Fund

Physics Department of the LMU Munich

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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