Identification of quinone analogues as potential inhibitors of picornavirus 3C protease in vitro

Bioorg Med Chem Lett. 2018 Aug 1;28(14):2533-2538. doi: 10.1016/j.bmcl.2018.05.046. Epub 2018 May 29.

Abstract

Picornaviruses are non-enveloped viruses that represent a large family of positive-sense single-stranded RNA viruses including a number of causative agents of many human and animal diseases such as coxsackievirus B3 (CVB3) and rhinoviruses (HRV). In this study, we performed a high-throughput screening of a compound library composed of ∼6000 small molecules in search of potential picornavirus 3C protease (3Cpro) inhibitors. As results, we identified quinone analogues that effectively inhibited both CVB3 3Cpro and HRV 3Cpro with IC50 values in low micromolar range. Together with predicted binding modes of these compounds to the active site of the viral protease, it is implied that structural features of these non-peptidic inhibitors may act as useful scaffold for further anti-picornavirus drug design and development.

Keywords: 3C protease inhibitors; Antivirals; Coxsackievirus B3; Picornavirus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3C Viral Proteases
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Benzoquinones / chemical synthesis
  • Benzoquinones / chemistry
  • Benzoquinones / pharmacology*
  • Cysteine Endopeptidases / metabolism
  • Dose-Response Relationship, Drug
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Protease Inhibitors / chemical synthesis
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology*
  • Rhinovirus / drug effects*
  • Rhinovirus / enzymology
  • Structure-Activity Relationship
  • Viral Proteins / antagonists & inhibitors*
  • Viral Proteins / metabolism

Substances

  • Antiviral Agents
  • Benzoquinones
  • Protease Inhibitors
  • Viral Proteins
  • quinone
  • Cysteine Endopeptidases
  • 3C Viral Proteases