Discovery of a novel compound against BmNPV using virtual screening based on the protein structure of the viral whole genome.

Currently, effective antiviral drugs against Bombyx mori nucleopolyhedrovirus (BmNPV) are still lacking, which has caused significant economic damage to the sericulture industry. Virtual screening and artificial intelligence provide opportunities for the discovery of antiviral drugs. To identify potential antiviral compounds against BmNPV through virtual screens, AlphaFold3-modelled viral proteins served as the targets. Among the tested compounds, octenidine dihydrochloride (OCT) was found to be a potential inhibitor that significantly inhibited BmNPV replication. Microscale thermophoresis and transmission electron microscopy revealed that OCT could bind with the BmNPV GP64 protein and inhibit the virus invasion. OCT could significantly improve the survival rate of B. mori larvae and exhibit promising therapeutic effects against BmNPV infection in vivo and field trials. Our findings have demonstrated the capacity to obtain antiviral drugs targeting the BmNPV genome through artificial intelligence-based prediction of protein structure and virtual screening. This serves as an important avenue for the development of effective antiviral drugs for veterinary use.