title: Group A streptococcus inhibitors by high-throughput virtual screening.
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.
authors.affiliation: Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, GA 30322, USA.
authors.forename: Haipeng
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, GA 30322, USA.
authors.forename: Shuli
authors.initials: S
authors.lastname: Mao
authors.affiliation: Department of Microbiology and Immunology, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA.
authors.forename: Julia V
authors.initials: JV
authors.lastname: Bugrysheva
authors.affiliation: Yerkes National Primate Research Center, Emory University, 201 Dowman Drive, Atlanta, GA 30322, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Pruett
authors.affiliation: Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, GA 30322, USA.
authors.forename: Dennis C
authors.initials: DC
authors.lastname: Liotta
authors.affiliation: Department of Microbiology and Immunology, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA.
authors.forename: June R
authors.initials: JR
authors.lastname: Scott
authors.affiliation: Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, GA 30322, USA. Electronic address: jsnyder@emory.edu.
authors.forename: James P
authors.initials: JP
authors.lastname: Snyder
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D057166:High-Throughput Screening Assays; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008968:Molecular Conformation; D012260:Ribonucleases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*; D013297:Streptococcus pyogenes / Q000166:cytology / Q000187:drug effects*; D013329:Structure-Activity Relationship; D016963:Thermus thermophilus / Q000201:enzymology
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D054852:Small Molecule Libraries; D012260:Ribonucleases
keywords: Group A streptococcus; High-throughput virtual screening (HTVS); Homology model; RNase J1/J2