African swine fever (ASF), caused by ASF virus (ASFV) infection, is a highly contagious and severe hemorrhagic viral disease with significant economic implications for the global pig farming industry. Currently, there are no effective vaccines or antiviral drugs available for controlling ASF epidemics. Developing effective strategies to combat this epidemic has become imperative. In this study, by screening a chemical library with 400 small molecule compounds, we identified that hycanthone, a previously used anthelminthic drug, exhibits the most potent inhibition on ASFV replication in PAMs, with an IC₅₀ value of 0.57 μmol/L. Hycanthone showed dose-dependent antiviral activity, reducing the mRNA levels of ASFV p30 and p72 proteins and decreasing viral DNA synthesis. Mechanistically, hycanthone attenuates ASFV replication by suppressing the cellular AKT phosphorylation and inducing viral DNA damage through interacting with ASFV AP endonuclease. Our findings suggest that hycanthone could serve as a promising therapeutic candidate for controlling ASFV infections.

To Cite This Article: Liu Z, Liu Y, Su G, Li H, Ou W, Chen W, Huangd L, Weng C and Chen J 2025. Hycanthone inhibits african swine fever virus replication by inhibiting the cellular AKT phosphorylation and inducing viral DNA damage in porcine alveolar macrophage cultures. Pak Vet J. http://dx.doi.org/10.29261/pakvetj/2025.228