Green silver nanoparticles of Khaya senegalensis as dual inhibitors of viral thymidine kinase and 3 C protease: metabolomics, and computational insights

To the best of our knowledge, this is the first study to evaluate green synthesized silver nanoparticles loaded Khaya senegalensis (Desr.) A. Juss. against HSV-1 and Coxsackie B4, while providing mechanistic insights through enzyme inhibition and in silico analyses. FTIR, HRTEM, UV–visible spectroscopy, particle size, and zeta potential analyses further characterized the nanoparticles, which exhibited colloidal stability (− 20.7 ± 5.26 mV), predominantly spherical morphology, and a core size of 8–38 nm by HRTEM. The larger hydrodynamic diameter observed by DLS (~ 463 nm) reflects the core plus capping biomolecules and solvation layer, consistent with effective nanoparticle stabilization. KS-AgNPs leaves showed the strongest antiviral effect against HSV-1 and Coxsackie B4, with an IC₅₀ of 99.65 ± 1.84 µg/mL. This was better than the crude leaf extract (116.26 ± 1.28 µg/mL) but less potent than the standard drug acyclovir (79.25 ± 0.14 µg/mL). Metabolomic profiling identified thirty secondary metabolites, with molecular docking and dynamics highlighting myricetin as a key antiviral compound (binding energies: −10.98 kcal/mol for thymidine kinase, − 9.42 kcal/mol for 3 C protease). Furthermore, pharmacokinetics, and ADME studies for myricetin was performed. In vitro enzyme inhibition assays confirmed suppression of thymidine kinase (IC₅₀ = 0.249 ± 0.007 µg/mL) and 3 C protease (IC₅₀ = 0.732 ± 0.028 µg/mL). The results indicate that biogenic KS-AgNPs have notable antiviral effects, and that metabolites from Khaya senegalensis may serve as potential candidates for future antiviral therapies.