Identification of a Potential Peptide Inhibitor of SARS-CoV-2 Targeting its Entry into the Host Cells

Drugs R D. 2020 Sep;20(3):161-169. doi: 10.1007/s40268-020-00312-5.

Abstract

Background and objective: Coronavirus disease (COVID-19) is an ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to the incessant spread of the disease with substantial morbidity and mortality rates, there is an urgent demand for effective therapeutics and vaccines to control and diminish this pandemic. A critical step in the crosstalk between the virus and the host cell is the binding of SARS-CoV-2 spike protein to the angiotensin-converting enzyme 2 (ACE2) receptor present on the surface of the host cells. Hence, inhibition of this interaction could be a promising strategy to combat the SARS-CoV-2 infection.

Methods: Docking and Molecular Dynamics (MD) simulation studies revealed that designed peptide maintains their secondary structure and provide a highly specific and stable binding (blocking) to SARS-CoV-2.

Results: We have designed a novel peptide that could inhibit SARS-CoV-2 spike protein interaction with ACE2, thereby blocking the cellular entry of the virus.

Conclusion: Our findings suggest that computationally developed inhibitory peptide may be developed as an anti-SARS-CoV-2 agent for the treatment of SARS-CoV-2 infection. We further plan to pursue the peptide in cell-based assays and eventually for clinical trials.

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Antiviral Agents / pharmacology
  • Betacoronavirus / isolation & purification
  • Betacoronavirus / metabolism*
  • COVID-19
  • Coronavirus Infections / prevention & control*
  • Coronavirus Infections / virology
  • Humans
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Pandemics / prevention & control*
  • Peptides / pharmacology*
  • Peptidyl-Dipeptidase A / metabolism
  • Pneumonia, Viral / prevention & control*
  • Pneumonia, Viral / virology
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus / metabolism*
  • Viral Vaccines / pharmacology

Substances

  • Antiviral Agents
  • Peptides
  • Spike Glycoprotein, Coronavirus
  • Viral Vaccines
  • spike protein, SARS-CoV-2
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2