Computational insights into Anacardium occidentale bioactives targeting PBP2a in MRSA infections

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ABSTRACT Antibiotic treatment is still difficult owing to the emergence of multidrug-resistant strains, namely Methicillin-Resistant Staphylococcus aureus (MRSA). Vancomycin/daptomycin-resistant enterococci (VRE) spread quickly and have become a major issue, necessitating alternative therapies for MRSA. This study aimed to investigate the medicinal properties of Anacardium occidentale , a widely used plant with numerous indigenous medicinal applications. Our primary goal was to identify potent phytoconstituents of A. occidentale with promising activity against MRSA. These phytoconstituents were extracted from the Indian Medicinal Plants, Phytochemistry and Therapeutics (IMMPAT) database, and their binding affinities were determined using molecular docking techniques. Molecular Mechanics/Generalized Born Surface Area (MM-GBSA) calculations of Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) and stability were performed by MD simulations of the ligand-protein complexes at 100ns. The results showed that leucodelphidin (-8.739 kcal/mol) and leucocyanidol (-8.375 kcal/mol) had the highest MRSA affinity scores, outperforming the reference compounds. Furthermore, MM-GBSA calculations revealed favorable binding energies, and the compounds exhibited satisfactory ADMET properties. At 100 ns, the MD simulation showed that the ligand and complex were stable. All phyto-constituents are harmless, according to toxicological evaluation through the database. Leucodelphidin, a potential phytoconstituent of A. occidentale with strong binding affinities against MRSA, was found in this investigation. This all-encompassing strategy, which incorporates toxicological evaluations and molecular dynamics simulations, increases the legitimacy of the potential therapeutic uses of these compounds.