High-throughput screening of natural antiviral drug candidates against white spot syndrome virus targeting VP28 in Penaeus monodon: Computational drug design approaches

[Display omitted] •A virtual library of 187 bioactive constituents from Azadirachta indica and Bacopa monnieri was created to fight WSSV.•Identified four potential antiviral compounds inhibiting the interaction between VP28 and PmRab7 in the endocytic pathway.•Epicatechin, kaempferol, luteolin, and apigenin showed strong binding affinities and favorable pharmacokinetic properties.•MD simulation and binding free energy analysis were conducted to confirm and elucidate intermolecular interactions.•Promising antiviral agents against WSSV, mitigating economic damage. The white spot syndrome virus (WSSV), considered the deadliest pathogen impacting Penaeid shrimp (Penaeus monodon), remains worrisome for the global shrimp industry due to its extreme virulence and mortality rate of up to 100%. To date, there has been no breakthrough in effective antivirals or vaccines that can mitigate the financial damage caused by the pathogen. The distinctive structure of VP28 facilitates its role as a trimer, serving as the primary envelope protein of WSSV. It anchors to the viral envelope, directly interacts with PmRab7, a membrane protein in P. monodon, and aids in entry into the host. This research aims to discover antiviral drug candidates targeting VP28 trimer by screening a virtual library of 187 bioactive compounds derived from the medicinal herbs Azadirachta indica and Bacopa monnieri. To evaluate the drug ability of compounds in restricting VP28 trimer interaction within the endocytic pathway, a computational strategy was employed, including virtual screening, pharmacokinetics and toxicity analysis, and molecular dynamics (MD) simulation. The four strongest compounds, epicatechin, luteolin, kaempferol, and apigenin, exhibited binding affinities of −8.8, −8.8, −8.7, and −8.5 Kcal/mol, respectively, and demonstrated excellent pharmacokinetic properties. Furthermore, we employed 100 nanoseconds MD simulations and MM-PBSA binding free energy calculations to examine intermolecular interactions and confirmed the structural stability of the compounds at the VP28 binding site. The findings of this research suggest that these compounds hold promise in combating WSSV infection, reducing economic losses, and contributing to the sustainability of the shrimp industry.