Discovery of Novel Red Algal Inhibitors Targeting African Swine Fever Virus dUTPase through Integrated Computational...

African swine fever virus (ASFV) is the causative agent of African swine fever, a highly lethal disease affecting domestic pigs and wild boars. Despite its first identification in East Africa in the early 1900s, no effective therapeutic drugs or vaccines are currently available. This study investigates the inhibitory potential of red algae-derived compounds against ASFV dUTPase, a key enzyme that prevents uracil misincorporation during viral DNA synthesis and maintains ge-nome fidelity.

Red algal compounds were curated from an extensive database and subjected to ADMET analysis to evaluate their pharmacokinetic properties. Binding interactions with ASFV dUTPase were analyzed using a consensus docking approach. Molecular dynamics simulations and binding free en-ergy calculations were then conducted to assess the stability and energetic favorability under swine physiological conditions. Off-target docking was performed to identify potential interactions with swine dUTPase and evaluate safety.

Among the compounds tested, thyrsenol A and 14-keto-dehydro-thyrsiferol, isolated from two Laurencia species, were identified as promising inhibitors of ASFV dUTPase. Both compounds demonstrated stable binding interactions with the target protein and strong binding affinities. Analy-sis of RMSD, RMSF, and hydrogen bond profiles further supported their stability. Off-target analysis indicated a low likelihood of interfering with swine dUTPase function.

These findings highlight red algae as a potential source for developing anti-ASFV ther-apeutics and pig feed supplements. Further in vitro and in vivo studies are warranted to validate these results and explore their practical applications in disease control.