Virtual Screening of Novel Non-Lactam Inhibitors Against CTX-M-15 β-Lactamase for Enhancement and Remodeling of Antibiotic Efficiency

Virtual Screening of Novel Non-Lactam Inhibitors

Abstract

Background & Objective: The CTX-M-15 are beta-lactamases that break down practically all the antibiotics that belong to the beta-lactam group resulting in antibiotic resistance in bacteria. Several beta-lactam inhibitors can be used in combination with different cephalosporin antibiotics to treat infections caused by microbes that produce the CTX-M-15 enzyme. This study aims to use a multi-step virtual screening strategy to screen three new non—lactam inhibitors against CTX-M-15.

Methods: A study was designed and conducted in the Department of Biotechnology at the University of Central Punjab.  A multi-step virtual screening strategy was used to screen three new non—lactam inhibitors against CTX-M-15. The CTX-M-15 binding sites were explored to determine the possible target sites of the inhibitors. Compounds from the E-LEA3D were subjected to virtual screening, and their performance was evaluated based on the binding energies and various other factors. Using Auto Dock Vina, the docking complexes were formed and visualized in Pymol where their RMSD values and binding energies were compared.

Results: The best results were found in the case of Isoproterenol as it inhibited the lactamase activity of CTX-M 15 by forming a stable docked complex. The molecular docking simulations using Autodock Vina revealed favorable binding interactions, indicating the ability of Isoproterenol to bind to the active site.

Conclusion: The lactamase activity of CTX-M 15 was inhibited by Isoproterenol as they form a stable docked complex. Designing inhibitors against the CTX-M-15 type β-lactamase represents a promising avenue for combating drug-resistant bacteria.