In silico Identification of Potential Quorum-Sensing Inhibitors Against the AgrA of Staphylococcus aureus

AgrA (Accessory gene regulator) plays a crucial role as a regulator in the agr quorum-sensing system by controlling the production of virulence factors, including exotoxins and enzymes involved in the pathogenesis of Staphylococcus aureus. The emergence of resistant strains highlights the urgent need for alternative therapeutic agents. Therefore, in this study, molecular docking of potential phytochemicals was performed against AgrA, followed by the evaluation of pharmacokinetic properties, allergenicity, and toxicity. Binding free energies were predicted using AutoDock Vina 1.5.6. Diosgenin, stigmasterol, hypericin, and betulin exhibited strong binding interactions with critical residues of AgrA, while colchicine, procyanidin B2, and quinine interacted with the transcriptional activation site of AgrA with high binding affinities, forming significant hydrogen bond interactions. The non-toxic, non-allergenic, and favorable pharmacokinetic properties of these compounds suggest that these phytochemicals could be developed into drugs for use in combination with antibiotics as adjuvants or synergists, pending further in vitro and in vivo evaluation.