Computational Identification of Phytochemical Inhibitors Against White Spot Syndrome Virus dUTPase: A Potential Antiviral Approach

Abstract

Background: White spot syndrome virus (WSSV) is a highly virulent pathogen threatening global shrimp populations, with no effective treatments available. Objectives: The present study aimed to identify antiviral compounds from Cyperus rotundus and Salvia rosmarinus targeting WSSV dUTPase using computational methods. Methods: A comprehensive analysis of phytochemicals included binding site prediction, protein structure validation, absorption, distribution, metabolism, and excretion (ADME) profiling, and compliance with the Lipinski rule. Molecular docking and dynamics simulations evaluated binding affinity and stability. Results: After screening 1103 compounds, 28 candidates qualified for docking. Notably, selinene, podolide, and zierone showed strong binding affinity to dUTPase with docking scores of -9.3, -8.8, and -7.8 kcal/mol, respectively, compared to the highest positive controls, 2’-deoxyuridine scored -6.6 kcal/mol. The ADME studies indicated favorable pharmacokinetic profiles. Molecular dynamics (MD) simulations over 100 ns confirmed stable binding interactions. Conclusions: The promising results from docking and dynamics simulations provide a foundation for advancing podolide and its analogs toward empirical validation. This research has potential for developing innovative phytochemical-derived antiviral interventions against WSSV, although in vivo validation is necessary to confirm efficacy and safety.