1. Group A streptococcus inhibitors by high-throughput virtual screening
- Author
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Sarah T. Pruett, Julia V. Bugrysheva, Dennis C. Liotta, June R. Scott, Haipeng Hu, Shuli Mao, and James P. Snyder
- Subjects
Models, Molecular ,Streptococcus pyogenes ,RNase P ,Molecular Conformation ,Microbial Sensitivity Tests ,medicine.disease_cause ,Group A ,Microbiology ,Small Molecule Libraries ,Structure-Activity Relationship ,Ribonucleases ,Drug Discovery ,medicine ,Bioassay ,Homology modeling ,Enzyme Inhibitors ,Pharmacology ,Virtual screening ,Dose-Response Relationship, Drug ,biology ,Chemistry ,Streptococcus ,Thermus thermophilus ,Organic Chemistry ,General Medicine ,biology.organism_classification ,Small molecule ,Anti-Bacterial Agents ,High-Throughput Screening Assays ,Bacteria - 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. more...
- Published
- 2014
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