Drug-resistant Staphylococcus aureus (DRSA) poses a significant global health threat, like bacteremia, endocarditis, skin, soft tissue, bone, and joint infections. Nowadays, the resistance against conventional drugs has been a prompt and focused medical concern. The present study aimed to explore the inhibitory potential of plant-based bioactive compounds (PBBCs) against effective target proteins using a computational approach. We retrieved and verified 22 target proteins associated with DRSA and conducted a screening process that involved testing 87 PBBCs. Molecular docking was performed between screened PBBCs and reference drugs with selected target proteins via AutoDock. Subsequently, we filtered the target proteins and top PBBCs based on their binding affinity scores. Furthermore, molecular dynamic simulation was carried out through GROMACS for a duration of 100 ns, and the binding free energy was calculated using the gmx_MMPBSA. The result showed consistent hydrogen bonding interactions among the amino acid residues Ser 149, Arg 151, Thr 165, Thr 216, Glu 239, Ser 240, Ile 14, as well as Asn 18, Gln 19, Lys 45, Thr 46, Tyr 109, with their respective target proteins of the penicillin-binding protein and dihydrofolate reductase complex. Additionally, we assessed the pharmacokinetic properties of screened PBBCs via SwissADME and AdmetSAR. The findings suggest that β-amyrin, oleanolic acid, kaempferol, quercetin, and friedelin have the potential to inhibit the selected target proteins. In future research, both in vitro and in vivo, experiments will be needed to establish these PBBCs as potent antimicrobial drugs for DRSA.Communicated by Ramaswamy H. Sarma.
Keywords: Drug-resistant Staphylococcus aureus (DRSA); binding free energy; gROMACS; mMPBSA; molecular docking; molecular dynamic simulation; pharmacokinetics studies; plant-based bioactive compounds.