Molecular interaction and inhibition of SARS-CoV-2 binding to the ACE2 receptor
Open accessPublished version of a preprint
Abstract
Study of the interactions established between the viral glycoproteins and their host receptors is of critical importance for a better understanding of virus entry into cells. The novel coronavirus SARS-CoV-2 entry into host cells is mediated by its spike glycoprotein (S-glycoprotein), and the angiotensin-converting enzyme 2 (ACE2) has been identified as a cellular receptor. Here, we use atomic force microscopy to investigate the mechanisms by which the S-glycoprotein binds to the ACE2 receptor. We demonstrate, both on model surfaces and on living cells, that the receptor binding domain (RBD) serves as the binding interface within the S-glycoprotein with the ACE2 receptor and extract the kinetic and thermodynamic properties of this binding pocket. Altogether, these results provide a picture of the established interaction on living cells. Finally, we test several binding inhibitor peptides targeting the virus early attachment stages, offering new perspectives in the treatment of the SARS-CoV-2 infection.
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Cardiomyocytes and pericytes express ACE2 and TMPRSS2, as well as other accessory proteins needed for viral infection by SARS-CoV-2.
“Thus, cardiomyocytes and pericytes express ACE2 and TMPRSS2, as well as other accessory proteins (ie, NRP1 [neuropilin-1 receptor], CD147 , integrin α 5 β 1, and cathepsin B/L) needed for viral infection by SARS-CoV-2”
From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [26]
The ‘Exploring the dynamics of S1 subunit–ACE2 interaction’ section reports spike binding to ACE2 on A549 lung-derived cells and discusses a possible role for integrins. It does not establish that cardiomyocytes or pericytes express ACE2, TMPRSS2, or the listed accessory proteins; nor does it identify integrin α5β1 specifically. Page numbers are unavailable in our copy. (LLM, conf=0.82)
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Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation
Wrapp, D., Wang, N., Corbett, K. S., Goldsmith, J. A., Hsieh, C.-L., Abiona, O., Graham, B. S., & McLellan, J. S. (2020) · Science · doi:10.1126/science.abb2507 · Cited by 8,897 · see citing works
Virus entry: molecular mechanisms and biomedical applications
Dimitrov, D. S. (2004) · Nature Reviews Microbiology · doi:10.1038/nrmicro817 · Cited by 701 · see citing works
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COVID-19 and pulmonary fibrosis: a potential role for lung epithelial cells and fibroblasts
John, A. E., Joseph, C., Jenkins, G., & Tatler, A. L. (2021) · Immunological Reviews · doi:10.1111/imr.12977 · Cited by 219 · see citing works
COVID-19, Myocarditis and Pericarditis
Fairweather, D., Beetler, D. J., Di Florio, D. N., Musigk, N., Heidecker, B., & Cooper, L. T. (2023) · Circulation Research · doi:10.1161/circresaha.123.321878 · Cited by 181 · see citing works
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- Authors
- Yang, J., Petitjean, S. J. L., Koehler, M., Zhang, Q., Dumitru, A. C., Chen, W., Derclaye, S., Vincent, S. P., Soumillion, P., & Alsteens, D.
- Affiliations
- UCLouvain (BE)
- University of Namur (BE)
- Walloon Excellence in Lifesciences and Biotechnology (BE)
- Corresponding author
- Alsteens, David
- ORCID
- Venue
- Nature Communications
- Published
- 2020-09-11
- Volume
- 11
- Issue
- 1
- Pages
- 4541-4541
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC7486399
- OpenAlex
- W3086712138
- Cited by
- 615
- References
- 2
- Citations by year
- 2026: 22 · 2025: 40 · 2024: 72 · 2023: 102 · 2022: 183 · 2021: 182 · 2020: 13 · 2019: 1
- FWCI
- 15.75
- Type
- journal article
- Language
- en
- Update notices
- correction (2021-05-14)
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Research Square (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Repository of the University of Namur (publishedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- European Commission (HORIZON2020)
- Fonds De La Recherche Scientifique - FNRS (CR-2019S-01)
- China Scholarship Council
- H2020 European Research Council (758224)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Physical Sciences › Physics and Astronomy › Atomic and Molecular Physics, and Optics › Force Microscopy Techniques and Applications
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 detection and testing
- Keywords
- SARS-CoV-2, ACE2 receptor, spike protein, receptor binding domain, viral entry, host receptor binding, binding kinetics, binding thermodynamics, peptide inhibitors, host-virus interaction
- MeSH terms
- A549 Cells, Betacoronavirus, Angiotensin-Converting Enzyme 2, COVID-19, SARS-CoV-2, Binding Sites, Humans, Peptidyl-Dipeptidase A, Models, Molecular, Pneumonia, Viral, Protein Binding, Receptors, Virus, Coronavirus Infections, Virus Attachment, Virus Internalization, Protein Interaction Domains and Motifs, Pandemics, Spike Glycoprotein, Coronavirus
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