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Molecular interaction and inhibition of SARS-CoV-2 binding to the ACE2 receptor.
Nat Commun. 2020 Sep 11; 11(1):4541.NC

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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Authors+Show Affiliations

Louvain Institute of Biomolecular Science and Technology, Université Catholique de Louvain, Louvain-la-Neuve, Belgium.

Louvain Institute of Biomolecular Science and Technology, Université Catholique de Louvain, Louvain-la-Neuve, Belgium.

Louvain Institute of Biomolecular Science and Technology, Université Catholique de Louvain, Louvain-la-Neuve, Belgium.

Louvain Institute of Biomolecular Science and Technology, Université Catholique de Louvain, Louvain-la-Neuve, Belgium.

Louvain Institute of Biomolecular Science and Technology, Université Catholique de Louvain, Louvain-la-Neuve, Belgium.

Départment de Chimie, Laboratoire de Chimie Bio-Organique, University of Namur, Namur, Belgium.

Louvain Institute of Biomolecular Science and Technology, Université Catholique de Louvain, Louvain-la-Neuve, Belgium.

Départment de Chimie, Laboratoire de Chimie Bio-Organique, University of Namur, Namur, Belgium.

Louvain Institute of Biomolecular Science and Technology, Université Catholique de Louvain, Louvain-la-Neuve, Belgium.

Louvain Institute of Biomolecular Science and Technology, Université Catholique de Louvain, Louvain-la-Neuve, Belgium. david.alsteens@uclouvain.be. Walloon Excellence in Life sciences and Biotechnology (WELBIO), 1300, Wavre, Belgium. david.alsteens@uclouvain.be.

MeSH

A549 CellsAngiotensin-Converting Enzyme 2BetacoronavirusBinding SitesCOVID-19Coronavirus InfectionsHumansModels, MolecularPandemicsPeptidyl-Dipeptidase APneumonia, ViralProtein BindingProtein Interaction Domains and MotifsReceptors, VirusSARS-CoV-2Spike Glycoprotein, CoronavirusVirus AttachmentVirus Internalization

Pub Type(s)

Journal Article

Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32917884

Citation

Yang, Jinsung, et al. "Molecular Interaction and Inhibition of SARS-CoV-2 Binding to the ACE2 Receptor." Nature Communications, vol. 11, no. 1, 2020, p. 4541.

Yang J, Petitjean SJL, Koehler M, et al. Molecular interaction and inhibition of SARS-CoV-2 binding to the ACE2 receptor. Nat Commun. 2020;11(1):4541.

Yang, J., Petitjean, S. J. L., Koehler, M., Zhang, Q., Dumitru, A. C., Chen, W., Derclaye, S., Vincent, S. P., Soumillion, P., & Alsteens, D. (2020). Molecular interaction and inhibition of SARS-CoV-2 binding to the ACE2 receptor. Nature Communications, 11(1), 4541. https://doi.org/10.1038/s41467-020-18319-6

Yang J, et al. Molecular Interaction and Inhibition of SARS-CoV-2 Binding to the ACE2 Receptor. Nat Commun. 2020 Sep 11;11(1):4541. PubMed PMID: 32917884.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - Molecular interaction and inhibition of SARS-CoV-2 binding to the ACE2 receptor. AU - Yang,Jinsung, AU - Petitjean,Simon J L, AU - Koehler,Melanie, AU - Zhang,Qingrong, AU - Dumitru,Andra C, AU - Chen,Wenzhang, AU - Derclaye,Sylvie, AU - Vincent,Stéphane P, AU - Soumillion,Patrice, AU - Alsteens,David, Y1 - 2020/09/11/ PY - 2020/7/9/received PY - 2020/8/18/accepted PY - 2020/9/12/entrez PY - 2020/9/13/pubmed PY - 2020/9/24/medline SP - 4541 EP - 4541 JF - Nature communications JO - Nat Commun VL - 11 IS - 1 N2 - 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. SN - 2041-1723 UR - https://www.unboundmedicine.com/medline/citation/32917884/Molecular_interaction_and_inhibition_of_SARS_CoV_2_binding_to_the_ACE2_receptor_ DB - PRIME DP - Unbound Medicine ER -