Virtual Screening for Potential Inhibitors of CTX-M-15 Protein of Klebsiella pneumoniae
- 131 Downloads
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.
KeywordsKlebsiella pneumoniae β-Lactamase CTX-M-15 Molecular docking Virtual screening
Compliance with Ethical Standards
Conflict of interest
The authors declare no competing financial interests in the findings of this study.
- 1.Brisse S, Grimont F, Grimont PAD (2006) The genus Klebsiella. Prokaryotes 6:159–196Google Scholar
- 7.Coque TM, Baquero F, Canton R (2008) Increasing prevalence of ESBL producing Enterobacteriaceae in Europe. Euro Surveill 13(47):pii_19044. http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId_19044
- 15.Farhadi T, Ranjbar MM (2017) Designing and modeling of complex DNA vaccine based on MOMP of Chlamydia trachomatis: an in silico approach. Netw Model Anal Health Inf Bioinf 6(1). doi: 10.1007/s13721-016-0142-5
- 16.Farhadi T, Ovchinnikov RS, Ranjbar MM (2016) In silico designing of some agonists of toll-like receptor 5 as a novel vaccine adjuvant candidates. Netw Model Anal Health Inform Bioinforma 5(31). doi: 10.1007/s13721-016-0138-1
- 28.Wolf LK (2009) New software and websites for the chemical enterprise. Chem Eng News 87:31Google Scholar
- 40.Podlogar BL, Muegge I, Brice LJ (2001) Computational methods to estimate drug development parameters. Curr Opin Drug Discov Dev 4:102–109Google Scholar