Targeting SARS-CoV-2 spike protein by stapled hACE2 peptides

Chem Commun (Camb). 2021 Apr 4;57(26):3283-3286. doi: 10.1039/d0cc08387a. Epub 2021 Mar 2.

Abstract

SARS-CoV-2 Spike protein RBD interacts with the hACE2 receptor to initiate cell entry and infection. We set out to develop lactam-based i,i + 4 stapled hACE2 peptides targeting SARS-CoV-2. In vitro screening demonstrates the inhibition of the Spike protein RBD-hACE2 complex formation by the hACE221-55A36K-F40E stapled peptide (IC50: 3.6 μM, Kd: 2.1 μM), suggesting that hACE2 peptidomimetics could form the basis for the development of anti-COVID-19 therapeutics.

MeSH terms

  • Amino Acid Sequence
  • Angiotensin-Converting Enzyme 2 / chemistry
  • Angiotensin-Converting Enzyme 2 / metabolism*
  • COVID-19 / metabolism*
  • COVID-19 / virology
  • Humans
  • Peptides / chemistry
  • Peptides / metabolism*
  • Peptidomimetics
  • SARS-CoV-2 / metabolism*
  • Spike Glycoprotein, Coronavirus / antagonists & inhibitors
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / metabolism*

Substances

  • Peptides
  • Peptidomimetics
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2