Background <p>This study investigates the antiviral potential of turmeric-derived compounds, particularly curcuminoids, against the Egyptian strain of Potato Virus Y (PVY^N-Egypt) using in silico molecular docking simulations. The binding interactions of five key compounds—curcumin, bisdemethoxycurcumin, demethoxycurcumin, isorhamnetin, and ribavirin (as a control)—were evaluated against three essential viral proteins: P1 protease, helper component proteinase (HCPro), and coat protein, to assess their therapeutic viability.</p> Results <p>Molecular docking results revealed that isorhamnetin exhibited the strongest binding affinity toward P1 protease. Curcumin and bisdemethoxycurcumin showed favorable binding to both HCPro and CP. ADMET profiling demonstrated that most tested ligands, except for curcuminol and ribavirin, had good oral bioavailability and favorable gastrointestinal absorption. Polar surface area (PSA), a key factor in membrane permeability and drug-likeness, was also considered—compounds with lower PSA values generally show better bioavailability. However, potential toxicity concerns were identified for curcuminol and ribavirin. Among the compounds, curcumin and its derivatives—particularly isorhamnetin—emerged as promising antiviral candidates, while bisdemethoxycurcumin showed potential to inhibit viral replication. Ribavirin displayed moderate binding but fewer favorable interactions compared to curcumin-based ligands.</p> Conclusion <p>This study provides new insights into the development of antiviral agents targeting PVY. The findings support the potential of curcumin derivatives, especially isorhamnetin and bisdemethoxycurcumin, as effective antiviral agents. Further experimental validation is recommended to explore their applications in agriculture and pharmaceutical biotechnology.</p>