Antiviral Potential of Brown Algal Metabolites Against A179L Anti-apoptotic Protein: A Computational Strategy for...

African swine fever virus poses a persistent threat to the global pork industry owing to its severe impact on animal welfare, the economy, and food security. Currently, no antiviral medicines are available, and biosecurity measures, such as quarantine and culling, have proven insufficient, often resulting in further economic losses. Given the widespread impact of ASFV, there is an urgent need to explore and develop new treatment strategies to mitigate its spread.

1,212 secondary metabolites from brown algae were screened using ADMET profiling. Compounds with favorable properties were selected for molecular docking against A179L, an antiapoptotic protein of ASFV. The top-scoring metabolites were further analyzed through molecular dynamics simulations, principal component analysis (PCA), and binding energy calculations.

ADMET profiling identified compounds with drug-like pharmacokinetic properties. Consensus molecular docking using two docking programs predicted the binding poses of the metabolites, and the top ten candidate ligands with the strongest docking scores were selected. We then performed 300 ns molecular dynamics simulations to assess the stability of the protein-ligand complexes, which were further validated through Principal Component Analysis (PCA). Finally, binding energies were estimated using both MMPBSA and MMGBSA approaches, and the key residues involved during binding were identified. All ten final candidate ligands demonstrated stability and favorable binding affinity (-27.78 kcal/mol to -38.58 kcal/mol).

Five compounds (CID: 24796376, sargachromanol G, strictaepoxide, CID: 163107957, and saringosterone) with the strongest binding energies are recommended for in vitro and in vivo testing to validate their potential as therapeutic agents against ASFV.