Computational Studies on the Exploration of Potential Metallo‐beta‐Lactamase Inhibitors From <i>Arrhenatherum elatius</i> : A Problematic Weed With Medicinal Properties

ABSTRACT Metallo‐beta‐lactamases (MBLs) are the Ambler class B beta‐lactam hydrolyzing enzymes, which can lead to the emergence of antimicrobial resistance. The rapid spreading of MBL‐mediated antimicrobial resistance in clinical bacterial isolates globally poses a serious challenge to most existing antimicrobial chemotherapies. There are very few clinically approved inhibitors against MBL enzymes, as most are still in the clinical trial stage. Thus, there is a highly urgent clinical need for developing effective new inhibitor drugs that specifically target the MBL‐producing bacteria. This work was conducted to explore potential inhibitors from the leaves of Arrhenatherum elatius for inhibiting MBL enzymes using bioinformatics. Molecular docking results showed that Cynaroside and Thermopsoside strongly bound to the MBL enzyme with the lowest binding energies of −5.9 and −6.0 kcal/mol, respectively, compared to the reference standard MBL substrate (Imipenem, −5.4 kcal/mol) and known inhibitor ( l ‐Captopril, −4.7 kcal/mol). Analysis of the molecular dynamics (MD) simulation trajectories predicted the stable conformation of Cynaroside and Thermopsoside in the presence of the MBL enzyme throughout the 200‐ns simulation time, confirming the observation made during molecular docking. This study noted that Cynaroside and Thermopsoside potentially have high affinities toward the MBL enzyme, which may act as competitive inhibitors of bacterial MBLs.