SARS-CoV-2 Binding and Neutralization Properties of Peptides Derived from N-Terminus of Human ACE2

Int J Mol Sci. 2023 May 5;24(9):8269. doi: 10.3390/ijms24098269.

Abstract

The binding properties of synthetic and recombinant peptides derived from N-terminal part of ACE2, the main receptor for SARS-CoV-2, were evaluated. Additionally, the ability of these peptides to prevent virus entry in vitro was addressed using both pseudovirus particles decorated with the S protein, as well as through infection of Vero cells with live SARS-CoV-2 virus. Surprisingly, in spite of effective binding to S protein, all linear peptides of various lengths failed to neutralize the viral infection in vitro. However, the P1st peptide that was chemically "stapled" in order to stabilize its alpha-helical structure was able to interfere with virus entry into ACE2-expressing cells. Interestingly, this peptide also neutralized pseudovirus particles decorated with S protein derived from the Omicron BA.1 virus, in spite of variations in key amino acid residues contacting ACE2.

Keywords: coronavirus variants; decoy receptor; human angiotensin-converting enzyme 2; spike protein; viral entry inhibition.

MeSH terms

  • Angiotensin-Converting Enzyme 2 / metabolism
  • Animals
  • COVID-19*
  • Chlorocebus aethiops
  • Humans
  • Peptides / metabolism
  • Peptides / pharmacology
  • Protein Binding
  • SARS-CoV-2* / metabolism
  • Vero Cells

Substances

  • Angiotensin-Converting Enzyme 2
  • Peptides