Background:The global spread of Strongyloides stercoralis has escalated public
health concerns, affecting over 600 million people worldwide. The rise in global migration has
heightened the risk of transmission, underscoring the urgent need for effective treatment options.Objective:This study aimed to investigate ten polyphenolic phytochemicals derived from Mangifera
indica as potential alternatives to combat S. stercoralis.Methods:The efficacy of these compounds was evaluated using computational techniques, including
density functional theory (DFT) analysis, molecular docking, adsorption, distribution,
metabolism, excretion, and toxicity (ADMET) assessment, and molecular dynamics (MD) simulations.Results:DFT calculations revealed significant chemical reactivity in compounds such as
kaempferol, ellagic acid, quercetin, norathyriol, mangiferin, and ferulic acid. Molecular docking
identified mangiferin, quercetin, kaempferol, and norathyriol as top candidates for targeting S.
stercoralis. A 200-ns MD simulation of the protein-ligand complex demonstrated the stability
and binding behavior of these compounds compared to the reference drug, thiabendazole. ADMET
screening confirmed their drug-likeness. Notably, quercetin and mangiferin exhibited
strong binding affinities (ΔGbind = -42.35 and -54.57 kcal/mol, respectively), outperforming
thiabendazole (ΔGbind = -28.94 kcal/mol).Conclusion:Quercetin and mangiferin emerge as promising alternatives to thiabendazole, offering
favorable chemical reactivity, potent inhibition constants, and strong biological activity for
the treatment of S. stercoralis.