Computationally driven molecular strategies of FDA-approved medications as potential inhibitors for the MurA and MurB enzymes to overcome antimicrobial resistance
Year: 2026
Type: article
Abstract: Antimicrobial resistance (AMR) has the potential to emerge serious healthcare threat in left unchecked and could put into motion another pandemic. With the advancement of bioinformatics, computational algorithms have been created to analyses large amounts of experimental data and identify biological macromolecules that can serve as targets for treating certain diseases. The study utilized a comprehensive computational strategy to pinpoint and prioritize existing FDA-approved medications as potential inhibitors for the MurA and MurB enzymes found in Pseudomonas aeruginosa and Acinetobacter baumannii. These enzymes are critical targets in the fight against AMR. By applying methods such as virtual screening, molecular docking, ADME-T (absorption, distribution, metabolism, excretion, and toxicity) profiling, and structure-activity relationship analysis, the study discovered high-affinity ligands exhibiting desirable drug-like characteristics. AbMurA was identified as the most promising candidate due to its clearly structured active site and robust interactions with ligands. Key catalytic residues such as Asp120, which are evolutionarily conserved, played a pivotal role in facilitating high-affinity binding. Compounds like Midostaurin (−13.451 kcal/mol) and M_Entrectinib (−12.8 kcal/mol) demonstrated notably strong binding capabilities in comparison, AbMurB ligands exhibited moderate binding strength (−10.142 kcal/mol). PaMurA ligands (e.g., Etoposide, −10.8 kcal/mol) displayed less favorable pharmacokinetic properties. Swiss ADME-based clustering analysis highlighted distinct differences in drug-like properties among the ligand groups, Cluster 1 ligands, like Fosnetupitant, exhibited poor bioavailability (0.14) due to excessive molecular flexibility. Overall, this study lays the groundwork for rational drug discovery efforts targeting AMR, with the ultimate goal of developing effective therapies to combat drug-resistant bacterial infections.
Institutions: Gyan Vihar University, REVA University
Language: English
Subfield: Drug Discovery
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W7169733232