Multi-target inhibitors of white spot syndrome virus envelope proteins (VP28, VP26, and VP24) to protect shrimp (Penaeus monodon): An integrated virtual screening, pharmacokinetic, and molecular dynamics study.

White Spot Syndrome Virus (WSSV) remains the most devastating pathogen in shrimp aquaculture worldwide, causing annual economic losses exceeding US$3 billion. To date, no effective prophylactic or therapeutic agents currently exist to mitigate the rapid, high-mortality outbreaks associated with WSSV. So, we employed an in silico framework, utilizing ClusPro 2.0, to map interactions between Penaeus monodon (host) receptors (Rab7, C-type lectin, GLUT-1, and β integrin) and the viral envelope proteins VP28, VP26, and VP24. The result of the protein-protein interactions guided to develop a multi-target strategy to inhibit the infection of WSSV. Then, a library of 2792 phytocompounds derived from 19 medicinal plant databases subjected to high-throughput virtual screening in PyRx-AutoDock Vina. Through a comprehensive investigation of the top hits using ADMET analysis and 100 ns molecular dynamics simulations, we identified 17α-hydroxywithanolide D and Withanolide G as the most promising compounds against VP28, VP26, and VP24. Both compounds demonstrated excellent multi-target binding affinity and thermodynamic stability. These findings provide a preliminary guide for a future sustainable, eco-friendly antiviral therapy. While these computational results are promising, further validation through in vitro and in vivo testing is necessary to confirm the efficacy of these candidates in aquaculture settings.