Abstract
Staphylococcus aureus, a prevalent component of the human microbiota, is associated with skin infections to life-threatening diseases, presenting challenges in treatment options and necessitating the development of effective treatments. This study integrated computational and in vitro approaches to identify promising phytocompounds with therapeutic potential. Staphopain B emerged as a target protein for its role in immune evasion, exhibiting stability during molecular dynamic simulation (MDS) with a root mean square deviation value of 2.376 Å. Screening 115 phytocompounds with antibacterial properties from the PubChem database identified 12 with drug-like properties, nine of which showed superior binding affinity to Staphopain B compared to a commercial antibiotic, doxycycline (-7.8 kcal mol(-1)). Notably, epoxyazadiradione and nimbolide displayed higher estimated free energy of binding scores (-7.91 and -7.93 kcal mol(-1), respectively), indicating strong protein-ligand interactions. The root mean square fluctuation values for epoxyazadiradione and nimbolide were 1.097 and 1.034 Å, respectively, which was confirmed through MDS. Crude ethanolic extracts (100% and 70%) of neem (Azadirachta indica) leaves demonstrated narrow inhibition against the bacteria in comparison to doxycycline in the disc-diffusion assay. This study underscores the potential of phytocompounds as therapeutic agents against S. aureus; however, further in vitro experiments and testing of the phytocompounds in vivo are required.