Molecular Docking Study of Small Plant-based Molecules for Inhibiting PBP2a Protein in Methicillin-Resistant Staphylococcus aureus (MRSA)

Abstract

Background: Antibiotic resistance, particularly in multidrug-resistant bacteria like Methicillin-Resistant Staphylococcus aureus (MRSA), poses a significant global health risk. The PBP2a protein is the major cause of MRSA resistance to beta-lactam antibiotics. This research was conducted in an "in silico" manner with the aim of identifying novel compounds with putative inhibitory activity against the PBP2a protein to overcome this resistance. The main goal of the article is to use molecular docking to find plant-based compounds that can serve as an alternative to antibiotics and help overcome MRSA bacterial resistance. Materials and Methods: This study was carried out using a descriptive-analytical method and molecular docking. First, the structure of the PBP2a protein and seven plant-based ligands were downloaded from the PDB and PubChem databases, respectively. The ligands included Allicin, Carvacrol, Thymol, Curcumin, Eugenol, Quercetin, and Terpinen-4-ol. For the docking simulation and visualization of the interaction between PBP2a and the ligands, we used Molegro Virtual Docker 6.0 and Molegro Molecular Viewer 2.5 software. Results and Conclusion: The results showed that Curcumin (ligand ID 969516) was bound to the protein with the best MolDock score of -281.131 kJ/mol. Based on its correct positioning and structural analysis, this compound can inhibit the enzymatic activity of PBP2a by binding to its active site. Accordingly, after further clinical studies, this compound is suggested as a suitable candidate for the treatment of MRSA infections. Quercetin (ligand ID 5280343) is also a strong candidate due to its high score of -279.218 kJ/mol. Conflict of interest: The authors declare no conflict of interest