IDENTIFICATION OF ANTIBACTERIAL AGENTS AGAINST KLEBSIELLA PNEUMONIAE TARGETING THE CTX-M-15 PROTEIN USING INTEGRATED STRUCTURE MODEL-BASED VIRTUAL SCREENING METHODS
Al-Maaqar S.M. Al-Johny B.O. Alshammari F.A. AL-Farga A. Molla M.H. Rebezov M. Kian S. Yakutina N. Rodionova S. Shariati M.A.
2024Slovak University of Agriculture
Journal of Microbiology, Biotechnology and Food Sciences
2024#14Issue 2
Background: The spread of carbapenem-resistant Gram-negative bacteria, particularly those having the bla CTX-M-15 gene, has stimulated a global challenge for β-lactam antimicrobial effectiveness. This study aims to identify commercially available compounds that demonstrate strong antibacterial properties with high efficacy and low toxicity to combat the increasing problem of antibiotic resistance. Methods: Virtual screening and molecular docking techniques were employed to generate a pharmacophore model based on the molecular structure. Eleven potential compounds were selected based on their IC50 values. Subsequently, a molecular docking approach was employed to select the best three small molecules for further comprehensive investigation. Moreover, absorption, distribution, metabolism, and excretion (ADME) and toxicity analysis ensured that it can be used as a drug without the effect of health. Finally, molecular dynamic (MD) simulations and generalized Born model and solvent accessibility (MMGB/SA) were carried out to evaluate the stability of these compounds against the receptor. Results: Three selected compounds, specifically ZINCCID (ZINC94211493, ZINC20528448, and ZINC04331046), have exhibited strong binding affinities of -8.4, -8.1, and -7.7 kcal/mol, respectively. This has been predicted as a potential competitive inhibitor targeting CTX-M-15. However, further assessment through experimental lab studies is required to evaluate the efficacy of these compounds. Conclusion: Initially, a structure-based model was constructed, and subsequently, molecular docking, MD simulation, ADMET analysis, and MMGB/SA were performed. Through the A-to-Z virtual screening process, the top three natural compounds were identified as potential lead molecules in the development of novel drugs targeting CTX-M-15 for combating Klebsiella infections.
ADMET , CTX-M-15 protein , Klebsiella , MD simulation , MMGB/SA , Molecular docking , Pharmacophore modeling , Structure-based
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Department of Biological Sciences, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah, 21589, Saudi Arabia
Department of Biology, Faculty of Education, Albaydha University, Al-Baydha, Yemen
Department of Biology, College of Science, Northern Border University, Arar, 76312, Saudi Arabia
Department of Biological Sciences, Faculty of Science, University of Jeddah, P.O. Box 80203, Jeddah, 21589, Saudi Arabia
Department of Scientific Research, V.M. Gorbatov Federal Research Center for Food Systems, 26 Talalikhin Str., Moscow, 109316, Russian Federation
Faculty of Biotechnology and Food Engineering, Ural State Agrarian University, 42 Karl Liebknecht str., Yekaterinburg, 620075, Russian Federation
Founder of Kian Academy, Fara Azmoon Arisa Lab, Karaj, Iran
Department of Physical Education, Kosygin State University of Russia, 1 Malaya Kaluzhskaya Str., Moscow, 119071, Russian Federation
Department of Scientific Research, K.G. Razumovsky Moscow State University of technologies and management, The First Cossack University, 73 Zemlyanoy Val, Moscow, 109004, Russian Federation
Kazakh Research Institute of Processing and Food Industry, Semey Branch of the Institute, 238«G» Gagarin Ave., Almaty, 050060, Kazakhstan
Department of Biological Sciences
Department of Biology
Department of Biology
Department of Biological Sciences
Department of Scientific Research
Faculty of Biotechnology and Food Engineering
Founder of Kian Academy
Department of Physical Education
Department of Scientific Research
Kazakh Research Institute of Processing and Food Industry
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