Virtual screening of plant‐derived molecules against zinc‐dependent imipenemases in class B metallo‐β‐lactamases of Acinetobacter baumannii

Abstract Metallo‐β‐lactamases (MBLs), enzymes of class B, employ zinc ions to degrade β‐lactam antibiotics such as penicillins, cephalosporins, carbapenems, and cephamycins. Carbapenem‐resistant Acinetobacter baumannii (CRAB) is linked to the existence of carbapenemase enzymes such as oxacillinase and MBL. The most prevalent resistance mechanisms include imipenemases (IMP), verona integron‐encoded MBL, and New Delhi MBL‐1. The effectiveness of current antibiotics against the MBL enzyme is limited due to the presence of metal ions, underscoring the need for new antimicrobial agents. Recent research has demonstrated that natural compounds can effectively inhibit MBL. This study aims to screen natural phytochemicals against IMP‐2 MBL using in silico virtual screening techniques via AutoDock Vina and molecular dynamic simulations with GROMACS for 200 ns, followed by molecular mechanics/Poisson‒Boltzmann surface area analysis. This procedure identified new lead molecules against A. baumannii that produce IMP. A total of 588 natural compounds were screened against IMP, along with the imipenem substrate and known inhibitors of L‐captopril. The top four compounds, N025‐0038 (NC1), N062‐0008 (NC2), eupalitin, and Rosmorinic acid, demonstrated binding affinities of ‒8.5, ‒8.4, ‒7.5, and ‒7.2 kcal/mol, respectively. The structural stability of these complexes was observed to be maintained throughout the simulation in a dynamic environment, as determined by molecular dynamics trajectory analysis, and all these compounds met the SWISS‐ADME (adsorption, distribution, metabolism, and excretion) properties. NC1 and NC2 compounds are considered potential drug molecules against IMP. However, while these selected compounds showed superior binding energy in computational analysis, further in vitro analysis is required to establish an effective drug regimen against A. baumannii that produces IMP.