In silico evaluation and therapeutic targeting of LVDD9B protein for WSSV inhibition: molecular and ecological insights for aquaculture solutions.

Unlabelled: This study aimed to investigate structural dynamics, binding interactions, stability, pharmacokinetics, ecological risks, and bioactivity of shrimp receptor protein LVDD9B to identify potential therapeutic candidates against White Spot Syndrome Virus (WSSV). LVDD9B protein's 3D structure was predicted using SWISS-MODEL and validated with ProSA and Ramachandran plots. Protein-protein docking between LVDD9B and VP26 (WSSV protein) was performed using HADDOCK 2.4 server. Molecular docking, dynamics simulations, binding-free energy calculations, principal component analysis (PCA), electrostatic, and vibrational frequency analyses evaluated binding affinity, stability and polarity of complexes. The 128-amino-acid LVDD9B protein was predominantly localized in the cytoplasm and extracellular with stable, and hydrophilic, with structural analysis identified key secondary structures and conserved chitin-binding sites. Docking studies revealed strong interactions between LVDD9B and VP26, supported by hydrogen-bonds and salt bridges. Molecular dynamics simulations demonstrated stable complexes with minimum fluctuating RMSF values, and MM/GBSA calculations indicated favourable binding free energies. Pharmacokinetic analysis highlighted promising bioavailability and drug-like properties for Luteolin and Quercetin from , while ecological assessment identified Cosmosiin as least hazardous, with Quercetin and Luteolin showing higher toxicity. PCA revealed stable protein-ligand complexes with flexibility in Apo form. Isorhoifolin exhibited the lowest internal energy (-2099.4722 Hartree) and highest dipole moment (8.1833 Debye). Frontier orbital analysis showed HOMO-LUMO gaps (4.05-4.34 eV) influencing reactivity, while MEP and vibrational frequency analyses supported compound stability and bioactivity. This study explores LVDD9B's structural and interaction dynamics for developing antiviral therapy against WSSV, highlighting therapeutic potential of Cosmosiin, Isorhoifolin and Afzelin based on their pharmacokinetic and ecological profiles.

Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-025-00390-w.