A virtual library of 388 marine bioactive compounds extracted from literatures published in Marine drugs Journal published by MDPI was used in this study.

The top ranking compounds from docking were chosen from the flexible docking based on the binding affinities (ΔGb).

In addition, the MD simulation and binding free energy analysis were implemented to validate and capture intermolecular interactions.

The results suggested that two compounds obtained a negative binding free energy with −40.453 KJ/mol and −31.031 KJ/mol for compounds with ids 30797199 and 144162 respectively.

The RMSD curve indicates 30797199 moves into the hydrophobic core, while the position of 144162 atoms changes abruptly during the simulation and is mostly stabilized by water bridges.

The shift in RMSD values of VP28 corresponding to ligand RMSD gives an insight into the ligand induced conformational changes in the protein.

This study is first of its kind to elucidate the explicit binding of chemical inhibitor to WSSV major structural protein VP28.