Group A streptococcus inhibitors by high-throughput virtual screening

Eur J Med Chem. 2014 Jul 23:82:120-6. doi: 10.1016/j.ejmech.2014.05.006. Epub 2014 May 4.

Abstract

Group A streptococcus (GAS) is a Gram-positive bacterium, which can cause multiple types of disease from mild infections of skin and throat to invasive and life-threatening infections. Recently RNase J1 and J2 were found to be essential for the growth of GAS. In order to identify inhibitors against RNase J1/J2, homology models of both the ligand-free apo-form and the ligand-bound holo-form complexes were constructed as templates for high-throughput virtual screening (HTVS). A focused small molecule library and the commercially available Maybridge database were employed as sources for potential inhibitors. A cell-based biological assay identified two compounds with 10 μM MIC activity.

Keywords: Group A streptococcus; High-throughput virtual screening (HTVS); Homology model; RNase J1/J2.

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • High-Throughput Screening Assays*
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Conformation
  • Ribonucleases / antagonists & inhibitors*
  • Ribonucleases / chemistry
  • Ribonucleases / metabolism
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Streptococcus pyogenes / cytology
  • Streptococcus pyogenes / drug effects*
  • Structure-Activity Relationship
  • Thermus thermophilus / enzymology

Substances

  • Anti-Bacterial Agents
  • Enzyme Inhibitors
  • Small Molecule Libraries
  • Ribonucleases