In silico identification of organosulfur compounds from Allium ascalonicum L. as potential inhibitors of influenza A (H5N1): integrated DFT, docking, and molecular dynamics analysis
Influenza A (H5N1) remains a major public health concern due to its high pathogenicity and ongoing viral evolution, underscoring the need for novel antiviral candidates. In this study, we performed an integrated in silico evaluation of organosulfur compounds derived from Allium ascalonicum L. (shallot) cultivated in the Tolaki-Mekongga region, Sulawesi, Indonesia, targeting key viral proteins including polymerase (PB2), nucleoprotein (NP), and neuraminidase (NA). Density functional theory (DFT) analyses were conducted to characterize the electronic properties of the compounds, while PASS prediction indicated moderate potential antiviral activity for Propanethiol and Dipropyl disulfide. Pharmacokinetic profiling suggested acceptable ADMET properties for several candidates. Molecular docking revealed favorable binding conformations across all targets, with γ-glutamyl-S-propenylcysteine exhibiting the most favorable binding energies among the evaluated organosulfur compounds (PB2: -4.9 kcal/mol; NP: -5.8 kcal/mol; NA: -5.2 kcal/mol). These values were comparable to those of oseltamivir and favipiravir for NP and NA, although weaker binding was observed against PB2. Subsequent simulations of molecular dynamics demonstrated stable protein–ligand complexes over 100 ns, further supporting the predicted binding interactions. Consistently, MM-GBSA calculations indicated favorable binding free energies, particularly for γ-glutamyl-S-propenylcysteine (PB2: -30.52 ± 0.29 kcal/mol; NP: -22.76 ± 0.12 kcal/mol; NA: -26.13 ± 0.35 kcal/mol). Overall, these findings suggest that shallot-derived organosulfur compounds, especially γ-glutamyl-S-propenylcysteine, exhibit potential for interaction with H5N1 viral targets and may warrant further investigation as antiviral candidates. Experimental validation through in vitro and in vivo studies is required to confirm their biological activity and therapeutic potential.