Abstract

African swine fever (ASF), caused by African swine fever virus (ASFV), is a highly contagious disease that has brought severe economic losses to the global swine industry. ASFV dUTPase is a key enzyme modulating viral nucleotide metabolism and genome stability, serving as a specific structural target for anti-ASF lead discovery. Based on the crystal structure of ASFV dUTPase (Georgia 2008/1 strain), we established a molecular docking model to virtually screen a Traditional Chinese Medicine (TCM) compound library following ADME-based filtration. We further conducted 100 ns molecular dynamics (MD) simulations via GROMACS and calculated binding free energies using the MM/PBSA method, followed by in vitro enzymatic inhibition assays for verification. Four candidate compounds, namely Salvianolic acid B, Kukoamine B, Ligustroflavone and 9′′′-Methyl salvianolic acid B, showed favorable structural accommodation and binding potential. In vitro tests indicated that Ligustroflavone and 9′′′-Methyl salvianolic acid B exhibited preliminary inhibitory activity against ASFV dUTPase, with IC50 values of 1.87 mM and 0.92 mM, respectively, while Kukoamine B showed no inhibitory effect. This study identified potential TCM-derived lead molecules targeting ASFV dUTPase, providing new references and candidate compounds for the development of anti-ASF therapeutics.

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