Identification of Natural Compounds as CTX-M-15 Inhibitors for the Management of Multidrug-Resistant Bacteria: An in-silico study

Mohammad Zubair Alam, Absarul Haque

Abstract


Background: Antibiotic resistance is a major global threat to the efficacy of bacterial infection treatment. Resistance to beta-lactam antibiotics in bacteria is primarily caused by the production of extended-spectrum-lactamases, with the CTX-M variant, particularly CTX-M-15, being the most common. The need for an effective CTX-M-15 inhibitor is currently pressing.

Methods: This study screened a library of natural compounds from the ZINC database against the CTX-M-15 protein using the PyRx 0.8 tool. The SwissADME web platform was used to predict the ADMET properties of the five most promising compounds.

Result: The identified hits compounds, ZINC1857626342, ZINC403692, ZINC408773, ZINC57926, and ZINC790938591 exhibited strong binding with CTX-M-15. These compounds interacted with crucial catalytic site residues in the CTX-M-15 protein, particularly Ser70 and Ser130. Notably, the binding energies of these compounds were higher than those of the reference compound avibactam. Furthermore, they exhibited pharmacologically favorable characteristics.

Conclusion: These compounds show promise as potential CTX-M-15 inhibitors to combat bacterial resistance. However, more experimental research is needed to optimize these compounds for their role as CTX-M-15 inhibitors.

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References


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DOI: http://dx.doi.org/10.62940/als.v10i4.2615

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