In Silico and In Vitro Screening of Natural Compounds as Broad-Spectrum β -Lactamase Inhibitors against Acinetobacter baumannii New Delhi Metallo- β -lactamase-1 (NDM-1).

Antibiotic resistance is one of the significant problems globally; there is an increase in resistance with introducing every new class of antibiotics. Further, this has become one of the reasons for arising of new resistance mechanisms in Acinetobacter baumannii . In this study, we have screened natural compounds as a possible inhibitor against the NDM-1 β -lactamase enzyme from A. baumannii using a combination of in silico methods and in vitro evaluation. The database of natural compounds was screened against NDM-1 protein, using Glide docking, followed by QM-polarised ligand docking (QPLD). When the screened hits were validated in vitro , withaferin A and mangiferin had good IC 50 values in reducing the activity of NDM-1 enzymes, and their fractional inhibitory concentration index (FICI) was ascertained in combination with imipenem. The withaferin A and mangiferin-NDM-1 docking complexes were analyzed for structural stability by molecular dynamic simulation analysis using GROMACS for 100 ns. The molecular properties of the natural compounds were then calculated using density functional theory (DFT). Withaferin A and mangiferin showed promising inhibitory activity and can be a natural compound candidate inhibitor synergistically used along with carbapenems against NDM-1 producing A. baumannii .