In silico evaluation of Eugenol binding to COX-2 and TRPV1: Supporting traditional use in toothache relief

Clove (Syzygium aromaticum) is commonly used in traditional remedies for tooth pain, mainly because of eugenol-a key active compound it contains. Although studies show eugenol can reduce pain and swelling, how exactly it affects major pain-related proteins isn't fully clear yet. This research looks at how eugenol binds to two vital signaling proteins linked to inflammation and pain perception: COX-2 and TRPV1 channels. Computational docking methods were applied to explore these interactions in detail. Instead of ibuprofen, which served as control substance, eugenol was processed following routine ligand preparation steps. Protein structures (COX-2 from PDB ID 5IKR; TRPV1 from PDB ID 7LPB) underwent refinement before being analyzed. Active binding pockets within them were detected using Molegro Virtual Docker software tools. Docking results showed eugenol binds moderately-but meaningfully-to COX-2 (score: −74.46), mainly via contacts with Arg120, Tyr355, and Ser530. Meanwhile, it also engaged strongly with the TRPV1 site (score: −61.07), where Glu684, Ala680, and Gly683 helped stabilize the complex. By contrast, ibuprofen achieved a deeper binding effect on COX-2 (−99.99), aligning with its known therapeutic strength. Because eugenol affects both inflammation-related targets and pain signaling routes, it may explain its historical use in easing toothaches. Overall, these data position eugenol as a viable plant-derived candidate for pain relief, warranting future studies using refined simulations, energy analysis, along with lab testing.