Computational Design of ACE2-Based Peptide Inhibitors of SARS-CoV-2

ACS Nano. 2020 Apr 28;14(4):5143-5147. doi: 10.1021/acsnano.0c02857. Epub 2020 Apr 16.

Abstract

Peptide inhibitors against the SARS-CoV-2 coronavirus, currently causing a worldwide pandemic, are designed and simulated. The inhibitors are mostly formed by two sequential self-supporting α-helices (bundle) extracted from the protease domain (PD) of angiotensin-converting enzyme 2 (ACE2), which bind to the SARS-CoV-2 receptor binding domains. Molecular dynamics simulations revealed that the α-helical peptides maintain their secondary structure and provide a highly specific and stable binding (blocking) to SARS-CoV-2. To provide a multivalent binding to the SARS-CoV-2 receptors, many such peptides could be attached to the surfaces of nanoparticle carriers. The proposed peptide inhibitors could provide simple and efficient therapeutics against the COVID-19 disease.

Keywords: COVID-19; SARS-CoV-2; molecular dynamics simulations; peptide inhibitors; therapeutics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Betacoronavirus / drug effects*
  • COVID-19
  • COVID-19 Drug Treatment
  • Computational Chemistry*
  • Coronavirus Infections / drug therapy*
  • Drug Design*
  • Humans
  • Molecular Dynamics Simulation*
  • Pandemics
  • Peptides* / chemistry
  • Peptides* / therapeutic use
  • Peptidyl-Dipeptidase A / chemistry*
  • Peptidyl-Dipeptidase A / drug effects
  • Pneumonia, Viral / drug therapy*
  • Protein Conformation
  • Protein Conformation, alpha-Helical
  • SARS-CoV-2

Substances

  • Peptides
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2