Group A streptococcus inhibitors by high-throughput virtual screening

•Homology models of RNase J1/J2 were developed as targets for Group A streptococcus.•High-throughput virtual screening (HTVS) was performed against 2 compound libraries.•Two compounds with 10 μM MIC activity were identified and characterized.•The HTVS strategy lays the groundwork for an extensive scaffold-hopping campaign.

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.

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