Marine fungal metabolites as antiviral agents: Computer-aided drug screening for selective inhibition of African swine fever virus dUTPase.

Introduction: African swine fever (ASF) continues to be a significant threat to the global livestock industry due to its severe impact on pig populations. Currently, there are no approved therapeutic agents for the virus, and biosecurity measures such as culling have led to substantial economic losses. In light of its effects on food security and the economy, our study aims to identify potential antiviral compounds from marine fungal metabolites that target the dUTPase enzyme of the African swine fever virus (ASFV). Methods: We screened 4,683 marine fungal metabolites using a series of virtual screening techniques. These included ADMET profiling to assess drug-likeness, consensus molecular docking to predict preferred docking poses and rank the docking scores, 300 ns molecular dynamics (MD) simulations to determine stability, principal component analysis (PCA) to verify simulation convergence, and MMPB(GB)SA analysis to estimate binding affinity. Results: Of the 4,683 compounds, 328 passed our ADMET filter, and the 10 highest-scoring ligands from molecular docking were evaluated for stability and binding affinity against both swine and ASFV dUTPase. Among the candidates, tricycloalternarene C (M1421), derived from Conclusion: Tricycloalternarene C holds potential as a selective inhibitor of ASFV dUTPase. We recommend further experimental validation to confirm its efficacy as an antiviral agent against African swine fever.