<i>In Silico</i> Evaluation of Anti-<i>SARS-CoV-2</i> Bioactive Compounds from <i>Jatropha curcas</i>

<i>Jatropha curcas</i> L., a medicinal shrub renowned for its diverse phytochemicals, has been traditionally used to treat various ailments, including ulcers, neoplasms, and dermatological conditions. Despite its pharmacological promise, its potential against <i>Severe Acute Respiratory Syndrome Coronavirus 2</i> (<i>SARS-CoV-2</i>) remains unexplored. This study investigates the antiviral efficacy of <i>J. curcas</i> phytochemicals targeting the <i>SARS-CoV</i>-2 main protease (M<sup>pro</sup>), a critical enzyme for viral replication, using advanced computational approaches. Molecular docking was employed to evaluate the binding affinity of 76 phytochemicals to M<sup>pro</sup>, with 47 compounds meeting stringent selection criteria. The stability of top-ranking complexes was assessed through 100-ns molecular dynamics simulations, analyzing parameters such as root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration, hydrogen bonding, solvent-accessible surface area (SASA), and interaction energies. Binding free energies were quantified using the Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) method, complemented by principal component analysis to elucidate dynamic behavior. The M<sup>pro</sup>-3-O-(Z)-coumaroyl oleanolic acid complex exhibited superior stability and favorable binding energetics. These findings highlight <i>J. curcas</i> as a promising source of novel inhibitors against <i>SARS-CoV-2</i> M<sup>pro</sup>, offering a foundation for future experimental validation and therapeutic development.