A computational investigation of potential plant-based bioactive compounds against drug-resistant Staphylococcus aureus of multiple target proteins

Abstract

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)
• plant-based bioactive compounds
• molecular docking
• molecular dynamic simulation
• gROMACS
• pharmacokinetics studies
• binding free energy
• mMPBSA

Acknowledgement

The authors acknowledge their gratitude to the Department of Biological Science and Engineering at MANIT, Bhopal, India. This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

Author contributions

Dr. Khushhali M. Pandey provided supervision, conceptualised the study, and finalised the original draft. Dr. Pallavi Chauhan contributed to editing the draft. Sudeesh Warkare conducted data analysis and curation. Sarit Prabha wrote the original draft, conceptualised it, and performed simulation.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.