Design, synthesis and molecular docking of novel triazole derivatives as potential CoV helicase inhibitors

Acta Pharm. 2020 Jun 1;70(2):145-159. doi: 10.2478/acph-2020-0024.

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) had emerged and spread because of the worldwide travel and inefficient healthcare provided for the infected patients in several countries. Herein we investigated the anti-MERS-CoV activity of newly synthesized sixteen halogenated triazole compounds through the inhibition of helicase activity using the FRET assay. All new compounds underwent justification for their target structures via microanalytical and spectral data. SAR studies were performed. Biological results revealed that the most potent compounds were 4-(cyclopent-1-en-3-ylamino)-5-(2-(4-iodophenyl)hydrazinyl)-4H-1,2,4-triazole-3-thiol (16) and 4-(cyclopent-1-en-3-ylamino)-5-[2-(4-chlorophenyl)hydrazinyl]-4H-1,2,4-triazole-3-thiol (12). In silico molecular docking of the most potent compounds was performed to the active binding site of MERS-CoV helicase nsp13. Molecular docking results are in agreement with experimental findings.

Keywords: MERS-CoV helicase; anti-MERS-CoV activity; docking; triazole derivatives.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / metabolism
  • Antiviral Agents / pharmacology*
  • Computer-Aided Design*
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / virology
  • DNA Helicases / antagonists & inhibitors*
  • DNA Helicases / chemistry
  • DNA Helicases / metabolism
  • Drug Design*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Middle East Respiratory Syndrome Coronavirus / drug effects*
  • Middle East Respiratory Syndrome Coronavirus / enzymology
  • Middle East Respiratory Syndrome Coronavirus / growth & development
  • Molecular Docking Simulation*
  • Molecular Structure
  • Protein Binding
  • Structure-Activity Relationship
  • Triazoles / chemical synthesis
  • Triazoles / metabolism
  • Triazoles / pharmacology*
  • Viral Proteins / antagonists & inhibitors*
  • Viral Proteins / chemistry
  • Viral Proteins / metabolism
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Enzyme Inhibitors
  • Triazoles
  • Viral Proteins
  • DNA Helicases