Unraveling the Molecular Mechanism of Curcumin Inhibition against White Spot Syndrome Virus VP۲۶: An Integrated Computational Study

Background: The White Spot Syndrome Virus (WSSV) poses a significant threat to global shrimp aquaculture, necessitating the development of effective antiviral agents. Among the structural proteins of WSSV, VP۲۶ plays a critical role in viral assembly and host-cell interactions, making it a promising target for therapeutic intervention. Curcumin, a bioactive compound derived from Curcuma longa, exhibits broad-spectrum antiviral potential, but its molecular mechanism of inhibition against WSSV remains unclear.Methods: An integrated computational approach combining molecular docking and molecular dynamics (MD) simulations was employed to elucidate the inhibitory interactions between curcumin and VP۲۶.Results: Docking results revealed a favorable binding affinity of –۶.۵۳ kcal/mol, indicating a spontaneous and stable interaction predominantly stabilized by van der Waals forces and hydrogen bonding, particularly involving Arg۱۳۶. Subsequent ۱۰۰ ns MD simulations demonstrated that the VP۲۶-curcumin complex maintained high structural stability, with consistent hydrogen bonding, short interatomic distances, and minimal deviation in the radius of gyration. Residue-specific flexibility analysis indicated localized increases in dynamics near the binding site, suggesting subtle conformational adaptation upon ligand binding. The MM/PBSA binding free energy (-۹۳.۴۶ kJ/mol) confirmed strong and stable complex formation.Conclusion: Collectively, these findings provide atomistic insights into the binding mechanism of curcumin with VP۲۶, supporting its potential as a natural antiviral inhibitor against WSSV and offering a foundation for the rational design of novel antiviral agents in aquaculture.Background: The White Spot Syndrome Virus (WSSV) poses a significant threat to global shrimp aquaculture, necessitating the development of effective antiviral agents. Among the structural proteins of WSSV, VP۲۶ plays a critical role in viral assembly and host-cell interactions, making it a promising target for therapeutic intervention. Curcumin, a bioactive compound derived from Curcuma longa, exhibits broad-spectrum antiviral potential, but its molecular mechanism of inhibition against WSSV remains unclear. Methods: An integrated computational approach combining molecular docking and molecular dynamics (MD) simulations was employed to elucidate the inhibitory interactions between curcumin and VP۲۶. Results: Docking results revealed a favorable binding affinity of –۶.۵۳ kcal/mol, indicating a spontaneous and stable interaction predominantly stabilized by van der Waals forces and hydrogen bonding, particularly involving Arg۱۳۶. Subsequent ۱۰۰ ns MD simulations demonstrated that the VP۲۶-curcumin complex maintained high structural stability, with consistent hydrogen bonding, short interatomic distances, and minimal deviation in the radius of gyration. Residue-specific flexibility analysis indicated localized increases in dynamics near the binding site, suggesting subtle conformational adaptation upon ligand binding. The MM/PBSA binding free energy (-۹۳.۴۶ kJ/mol) confirmed strong and stable complex formation. Conclusion: Collectively, these findings provide atomistic insights into the binding mechanism of curcumin with VP۲۶, supporting its potential as a natural antiviral inhibitor against WSSV and offering a foundation for the rational design of novel antiviral agents in aquaculture.

کلیدواژه ها:

White Spot Syndrome Virus ، Curcumin ، Molecular Docking ، Molecular Dynamics Simulations