In silico identification of multi-target inhibitors from medicinal fungal metabolites against the base excision repair pathway proteins of African swine fever virus

Abstract

African swine fever virus (ASFV) has emerged as a serious threat to the pork industry resulting in significant economic losses and heightened concerns about food security. With no known cure presently available, existing control measures center on animal quarantine and culling. Considering the severity and challenges posed by ASFV, it is imperative to discover new treatment strategies and implement additional measures to prevent its further spread. This study recognized the potential of 1830 fungal metabolites from medicinal fungi as antiviral compounds against base excision repair (BER) proteins of ASFV, specifically ASFVAP, ASFVPolX, and ASFVLig. A wide array of computer-aided drug discovery techniques were employed to carry out the virtual screening process: ADMET profiling revealed 319 molecules with excellent bioavailability and toxicity properties; consensus docking identified the 10 best-scoring ligands against all targets; molecular dynamics simulation elucidated the stability of the protein-ligand complexes; and MM/PB(GB)SA energy calculations predicted the binding energies of the compounds as well as the key residues integral to binding. Through in silico methods, we identified two theoretical lead candidates against ASFVAP, four against ASFVLig, and five against ASFVPolX. Two compounds, methyl ganoderate E and antcamphin M, exhibited potential multi-target inhibitory characteristics against ASFVPolX and ASFVLig, while compound cochlactone A showed promising antagonistic results against all three BER proteins. It is recommended to prioritize these hit compounds in future in vitro and in vivo studies to validate their potential as antiviral drugs against ASFV.