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
N1 - Funding Information:
This work was supported by the Université catholique de Louvain, the Foundation Louvain, and the Fonds National de la Recherche Scientifique (FRS-FNRS). This project received funding from the European Research Council under the European Union’s Horizon 2020 research and innovation program (grant agreement No. 758224) and from the FNRS-Welbio (Grant # CR-2019S-01). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the paper. S.P., A.C.D., and D.A. are research fellow, postdoctoral researcher, and research associate at the FNRS, respectively. Q.Z., W.C., and S.P.V. are grateful to China Scholarship Council.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85090904541&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-18319-6
DO - 10.1038/s41467-020-18319-6
M3 - Article
C2 - 32917884
AN - SCOPUS:85090904541
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 4541
ER -
