Mark Andrian B. Macalalad
1,2 
, Fredmoore L. Orosco
1,3,4* 1 Virology and Vaccine Research Program, Department of Science and Technology - Industrial Technology Development Institute, Taguig, Metro Manila, 1631, Philippines
2 Career Incentive Program, Department of Science and Technology – Science Education Institute, Taguig, Metro Manila, 1631, Philippines
3 S&T Fellows Program, Department of Science and Technology, Taguig, Metro Manila, 1631, Philippines
4 The UPLB Graduate School, University of the Philippines Los Baños, Los Baños, Laguna, 4031, Philippines
*Corresponding Author: Department of Biology, College of Arts and Sciences, University of the Philippines – Manila, Manila, Metro Manila, 1000, Philippines Email orosco.fredmoore@gmail.com
Abstract
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 Alternaria sp., emerged as a promising candidate. It exhibited excellent drug-likeness, stability, and binding affinity comparable to the three control compounds, while showing less affinity towards the swine dUTPase.
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.