In Silico Analysis of an Antidiabetic Drug Canagliflozin as a Potential Inhibitor of Penicillin‐Binding Protein 3 in Acinetobacter baumannii

ABSTRACT

Acinetobacter baumannii ( A. baumannii ) stands as a critical priority pathogen, rapidly developing resistance against the currently available antibiotic treatments, including last‐resort antibiotics. This nosocomial pathogen is responsible for alarmingly high mortality rates across the world. The drug repurposing approach may aid effectively in this crucial situation as the pharmacokinetic profile and safety details of currently available drugs are already well known, thereby taking comparatively less time than the traditional drug development process. In this study, the Food and Drug Administration (FDA) sanctioned drugs with structural similarity to ampicillin were screened, followed by pharmacokinetic and antimicrobial activity evaluations via in silico analysis. Further, the binding affinity of the drugs toward penicillin‐binding protein 3 (PBP3) and its prevalent mutants was evaluated via molecular docking and simulation studies. Based on results, the antidiabetic drug canagliflozin has been found to possess good binding affinity with wild type penicillin‐binding protein 3 (PBP3 _WT) (−8.01 kcal/mol), as well as its clinically prevalent mutants, PBP3 _A515V (−7.76 kcal/mol), PBP3 _T526S (−7.26 kcal/mol). According to our results, the drug possesses stable molecular dynamics interactions with PBP3 _WT , as well as its mutants, PBP3 _A515V and PBP3 _T526S . Based on our observations, we suggest canagliflozin as a potent PBP3‐binding drug against the A. baumannii pathogen.