Repurposing FDA approved drug molecules against A B C classes of β-lactamases: a computational biology and molecular dynamics simulations study

β-lactamase are the main resistance factor for β-lactam Antibiotics in Gram-negative bacteria. Since β-lactam Antibiotics are being utilised as an antimicrobial agents extensively for the past 70 years, a large number of β-lactam-inactivating β-lactamases have been produced by bacteria. Here, we employed a structure-based drug discovery approach to identify and assess the efficacy of a potential medication that might block the β-lactamases which hydrolyse Antibiotics. The FDA-approved medications were subjected to virtual screening, molecular docking, molecular dynamics simulations, density functional theory, and covalent docking against the β-lactamases. We identified diosmin, hidrosmin, monoxuritin and solasulfone as β-lactamase inhibitors which are authorised for therapeutic use in humans. These medications interact in a remarkable variety of non-covalent ways with the conserved residues in the substrate-binding pocket of the β-lactamases. Diosmin has been identified as an inhibitor that binds covalently to the NDM-1 a class B metallo-betalactamase. After experimental validation and clinical demonstration, this study offers adequate evidence for the therapeutic use of these drugs for controlling multidrug resistance.Communicated by Ramaswamy H. Sarma.