<i>In Silico</i> Exploration of Flavonoids as SPPV14 Inhibitors: Potential Antiviral Agents for Sheep Pox Virus

Sheep pox virus (SPPV) presents considerable economic and health challenges, in particular for agricultural areas relying on sheep farming. SPPV encodes for SPPV14, a strong inhibitor of BCL-2-mediated apoptosis, which has sparked interest in identifying and developing multifaceted therapeutics. The SPPV14 protein is currently noticed as a crucial viral aspect that facilitates infection and advances the progression of the disease. Recent studies indicate that flavonoids, which are naturally occurring compounds known for their strong antiviral properties, could offer a promising strategy to inhibit SPPV infection. The current study attempted to explore the inhibitory ability of specific flavonoids on the SPPV14 protein utilizing an in silico molecular docking approach. A selection of ten flavonoids was made for virtual screening and docking studies aimed at the active site of the SPPV14 protein, emphasizing interactions at the Arg84 residue, which is essential for the stability of the viral protein. Using AutoDock Vina, molecular docking simulations were run to assess the binding affinities and possible inhibitory effects of flavonoids. All examined flavonoids exhibited significant binding affinities to SPPV14, with isoxanthohumol showing a remarkable interaction with the Arg84 residue, indicating increased stability in binding and possible inhibitory effects. The chosen flavonoids eliminated the canonical ionic interaction observed in all sheep pox disease SPPV14:BH3 motif complex resulting in apoptosis in SPPV14 docking investigation. These interactions suggest that flavonoids may have the ability to interfere with viral protein function, which may hinder the development of SPPV. &lt;i&gt;In silico&lt;/i&gt; analysis suggests that specific flavonoids could act as effective antiviral agents against SPPV, with a particular focus on SPPV14. The findings establish a basis for following in vitro and in vivo investigations with the purpose of confirming the potential of flavonoids as alternative therapeutic agents for the management of sheep pox.