title: Virtual Screening for Potential Inhibitors of CTX-M-15 Protein of Klebsiella pneumoniae.
abstract: The Gram-negative bacterium Klebsiella pneumoniae, responsible for a wide variety of nosocomial infections in immuno-deficient patients, involves the respiratory, urinary and gastrointestinal tract infections and septicemia. Extended spectrum β-lactamases (ESBL) belong to β-lactamases capable of conferring antibiotic resistance in Gram-negative bacteria. CTX-M-15, a prevalent ESBL reported from Enterobacteriaceae including K. pneumoniae, was selected as a potent anti-bacterial target. To identify the novel drug-like compounds, structure-based screening procedure was employed against downloaded drug-like compounds from ZINC database. An acronym for "ZINC" is not commercial. The docking free energy values were investigated and compared to the known inhibitor Avibactam. Six best novel drug-like compounds were selected and their hydrogen bindings with the receptor were determined. Based on the binding efficiency mode, three among these six identified most potential inhibitors, ZINC21811621, ZINC93091917 and ZINC19488569, were predicted as potential competitive inhibitors against CTX-M-15 compared to Avibactam. These three inhibitors may provide a framework for the experimental studies to develop anti-Klebsiella novel drug candidates targeting CTX-M-15.
authors.affiliation: Chronic Respiratory Diseases Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, P.O.Box 19569-44413, Tehran, Iran.
authors.forename: Tayebeh
authors.initials: T
authors.lastname: Farhadi
authors.affiliation: Chronic Respiratory Diseases Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, P.O.Box 19569-44413, Tehran, Iran. fakharian_2005@yahoo.com.
authors.forename: Atefeh
authors.initials: A
authors.lastname: Fakharian
authors.affiliation: Microbiology Group, Department of Bioactive Nanostructures, Federal Research Centre for Microbiology and Epidemiology, n.a. N.F. Gamaleya, Moscow, Russia.
authors.forename: Roman S
authors.initials: RS
authors.lastname: Ovchinnikov
mesh_terms: D053961:Azabicyclo Compounds / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000032:analysis* / Q000737:chemistry / Q000494:pharmacology*; D007711:Klebsiella pneumoniae / Q000201:enzymology*; D008024:Ligands; D062105:Molecular Docking Simulation; D008970:Molecular Weight; D001618:beta-Lactamases / Q000737:chemistry / Q000378:metabolism*
chemical_list: D053961:Azabicyclo Compounds; D004791:Enzyme Inhibitors; D008024:Ligands; C543519:avibactam; C473109:beta-lactamase CTX-M-15; D001618:beta-Lactamases
keywords: CTX-M-15; Klebsiella pneumoniae; Molecular docking; Virtual screening; β-Lactamase