Exploring antiviral strategies to combat African swine fever

African swine fever (ASF), caused by the highly contagious African swine fever virus (ASFV), poses a significant threat to domestic and wild pigs worldwide. Despite its limited host range and lack of zoonotic potential, ASF has severe socio-economic and environmental consequences. Current control strategies primarily rely on early detection and culling of infected animals, but these measures are insufficient given the rapid spread of the disease. Developing effective therapeutics against ASFV is crucial to prevent further spread and mitigate economic losses. Although vaccination remains critical, recent vaccine approvals in Vietnam have raised safety and efficacy concerns. Moreover, as challenges persist in vaccine development and deployment, particularly in complex field conditions, antiviral agents have emerged as a critical complementary approach. These agents have the potential to mitigate side effects and control viral spread when vaccines alone are insufficient or when animals face simultaneous exposure to vaccine strains and wild-type viruses. However, advancing them from proof-of-concept to widespread practical application entails a significant interdisciplinary effort, given the logistical and economic constraints of in vivo testing. In this review, we examine emerging antiviral approaches and highlight key ASFV replication mechanisms and therapeutic targets to guide rational drug design amidst an evolving viral landscape.