Identification of novel inhibitors of methionyl-tRNA synthetase (MetRS) by virtual screening

Multiple inhibitors of the antibacterial target, Staphylococcus aureus MetRS, were identified by virtual screening. The process consisted of building a Catalyst® pharmacophore from a ligand-S. aureus MetRS structure and using this pharmacophore to screen a commercial database. The top hits from this search were then docked into the S. aureus MetRS structure and this information was used to select compounds for testing. This resulted in a high hit rate of compounds that are in distinct structural classes from the known MetRS ligands.

Graphical abstractMultiple inhibitors of the antibacterial target, Staphylococcus aureus MetRS, were identified by virtual screening. The process consisted of building a Catalyst® pharmacophore from a ligand-S. aureus MetRS structure and using this pharmacophore to screen a commercial database. The top hits from this search were then docked into the S. aureus MetRS structure and this information was used to select compounds for testing. This resulted in a high hit rate of compounds that are in distinct structural classes from the known MetRS inhibitors.Figure optionsDownload full-size imageDownload as PowerPoint slide