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Virtual Screening for Potential Inhibitors of CTX-M-15 Protein of Klebsiella pneumoniae

  • Tayebeh Farhadi
  • Atefeh Fakharian
  • Roman S. Ovchinnikov
Original Research Article

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.

Keywords

Klebsiella pneumoniae β-Lactamase CTX-M-15 Molecular docking Virtual screening 

Notes

Compliance with Ethical Standards

Conflict of interest

The authors declare no competing financial interests in the findings of this study.

Supplementary material

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Copyright information

© Springer-Verlag 2017

Authors and Affiliations

  • Tayebeh Farhadi
    • 1
  • Atefeh Fakharian
    • 1
  • Roman S. Ovchinnikov
    • 2
  1. 1.Chronic Respiratory Diseases Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD)Shahid Beheshti University of Medical SciencesTehranIran
  2. 2.Microbiology Group, Department of Bioactive NanostructuresFederal Research Centre for Microbiology and EpidemiologyMoscowRussia

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