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

Nat Commun. 2020 Sep 11;11(1):4541. doi: 10.1038/s41467-020-18319-6.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Angiotensin-Converting Enzyme 2
  • Betacoronavirus / metabolism
  • Betacoronavirus / physiology*
  • Binding Sites
  • COVID-19
  • Coronavirus Infections / metabolism
  • Coronavirus Infections / virology*
  • Humans
  • Models, Molecular
  • Pandemics
  • Peptidyl-Dipeptidase A / chemistry
  • Peptidyl-Dipeptidase A / metabolism*
  • Pneumonia, Viral / metabolism
  • Pneumonia, Viral / virology*
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Receptors, Virus / metabolism
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / metabolism*
  • Virus Attachment*
  • Virus Internalization*

Substances

  • Receptors, Virus
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2