Molecular Docking and In-Silico Analysis of Natural Biomolecules against Dengue, Ebola, Zika, SARS-CoV-2 Variants of Concern and Monkeypox Virus

Int J Mol Sci. 2022 Sep 22;23(19):11131. doi: 10.3390/ijms231911131.

Abstract

The emergence and rapid evolution of human pathogenic viruses, combined with the difficulties in developing effective vaccines, underline the need to develop innovative broad-spectrum antiviral therapeutic agents. The present study aims to determine the in silico antiviral potential of six bacterial antimicrobial peptides (AMPs), two phytochemicals (silvestrol, andrographolide), and two bacterial secondary metabolites (lyngbyabellin A, hapalindole H) against dengue virus, Zika virus, Ebola virus, the major variants of SARS-CoV-2 and monkeypox virus. The comparison of docking scores obtained with natural biomolecules was performed with specific neutralizing antibodies (positive controls for ClusPro) and antiviral drugs (negative controls for Autodock Vina). Glycocin F was the only natural biomolecule tested to show high binding energies to all viral surface proteins and the corresponding viral cell receptors. Lactococcin G and plantaricin ASM1 also achieved high docking scores with all viral surface proteins and most corresponding cell surface receptors. Silvestrol, andrographolide, hapalindole H, and lyngbyabellin A showed variable docking scores depending on the viral surface proteins and cell receptors tested. Three glycocin F mutants with amino acid modifications showed an increase in their docking energy to the spike proteins of SARS-CoV-2 B.1.617.2 Indian variant, and of the SARS-CoV-2 P.1 Japan/Brazil variant, and the dengue DENV envelope protein. All mutant AMPs indicated a frequent occurrence of valine and proline amino acid rotamers. AMPs and glycocin F in particular are the most promising biomolecules for the development of broad-spectrum antiviral treatments targeting the attachment and entry of viruses into their target cell.

Keywords: Ebola; SARS-CoV-2; Zika; bacterial AMPs; biomolecules; dengue; molecular docking; monkeypox.

MeSH terms

  • Amino Acids
  • Antibodies, Neutralizing / therapeutic use
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • Benzofurans
  • COVID-19 Drug Treatment*
  • Dengue* / drug therapy
  • Diterpenes
  • Hemorrhagic Fever, Ebola* / drug therapy
  • Humans
  • Molecular Docking Simulation
  • Monkeypox virus / metabolism
  • Proline / therapeutic use
  • SARS-CoV-2 / genetics
  • Spike Glycoprotein, Coronavirus / metabolism
  • Valine / therapeutic use
  • Zika Virus* / genetics
  • Zika Virus* / metabolism

Substances

  • Amino Acids
  • Antibodies, Neutralizing
  • Antiviral Agents
  • Benzofurans
  • Diterpenes
  • Spike Glycoprotein, Coronavirus
  • silvestrol
  • spike protein, SARS-CoV-2
  • andrographolide
  • Proline
  • Valine

Supplementary concepts

  • SARS-CoV-2 variants

Grant support

This work has been supported by CNRS GDR 2088 “BIOMIM”.