Potential of Nephrolepis exaltata as a Promising Antibacterial Agent against Methicillin-Resistant Staphylococcus aureus (MRSA): A Comprehensive in silico and in vitro Study

Recently, the emergence of bacteria impenetrable to antibiotics has led to a devastating situation concerning international health. This study identified one of the most threatening bacteria, methicillin-resistant Staphylococcus aureus. The potential antibacterial properties of Neprolepis exaltata include its ability to inhibit the growth of Staphylococcus aureus. Methicillin-resistant Staphylococcus aureus (MRSA) is not effectively susceptible to methicillin antibiotics. Methanolic crude extracts of Neprolepis exaltata were tested against Methicillin-resistant Staphylococcus aureus at 30 μg/mL and 40 μg/mL concentrations using the agar disc diffusion technique; 18 mm and 20 mm inhibition zones were reported. Furthermore, the dilution method, the crude extract's minimum inhibitory concentration (MIC) was tested against Methicillin-resistant Staphylococcus aureus at concentrations of 20, 40, 60, 80, and 100 μg/mL. The MIC value of the crude extract was found to be 40 μg/mL. Furthermore, crude methanolic extracts of Neprolepis exaltata were subjected to GC-MS analysis, and 22 phytochemicals were identified. Compound 2, 3-Diazabicyclo [2.2.1] hept-2-ene, has shown the highest binding affinity of -6.6 kcal/mol based on molecular docking. Molecular dynamics (MD) simulations determine the structural dynamics of the sphingosine kinase 1 complex with ligands (2ME, BEN, ARC). Factors such as RMSD, RMSF, Rg, SASA, and H bonding were examined to investigate the dynamic changes in ligand binding. The RMSD revealed stable equilibration within 10 ns, illustrating stability throughout the 100 ns simulation. The RMSF results indicate that ligand binding influences the flexibility of the protein, as indicated by the lower fluctuations for 2ME and BEN. Ligand binding increased solvent accessibility, and the greater compactness of the complex systems was indicated by Rg and SASA values. The stable interactions of H bonds were examined, and principal component analysis confirmed the lower flexibility of the ligand-bound complexes. The MM-PBSA method revealed the binding affinity of van der Waal energy, electrostatic energy, polar solvation energy, and binding energy of 1MWS-2ME, 1MWS-BEN, and 1MWS-ARC.