Molecular interaction and inhibition of SARS-CoV-2 binding to the ACE2 receptor

Yang, Jinsung; Petitjean, Simon J. L.; Koehler, Melanie; Zhang, Qingrong; Dumitru, Andra C.; Chen, Wenzhang; Derclaye, Sylvie; Vincent, Stéphane P.; Soumillion, Patrice; Alsteens, David

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.