Mechanistic insights and therapeutic advances in antiviral strategies against African swine fever virus

African swine fever virus (ASFV) causes a highly contagious and lethal disease in domestic and wild pigs, posing a significant threat to global swine production. The lack of effective vaccines or antiviral therapies underscores the urgent need for alternative intervention strategies. In recent years, notable progress has been made in developing antiviral agents that target both viral components and host-dependent pathways. This review provides a comprehensive summary of recent advances in ASFV antiviral research, with a focus on therapeutic interventions aimed at viral-encoded proteins and host factors, particularly small-molecule inhibitors and their mechanisms of action. In addition, the review highlights target-agnostic and multifaceted antiviral strategies, including physical inactivation, early life cycle disruption, and gene-level interference, which act through broad or partially understood mechanisms. By integrating mechanistic insights with emerging therapeutic approaches, this review supports the rational design of antiviral interventions against ASFV and informs the subsequent exploration of candidate drugs with clinical translational potential. The graphical abstract depicts contemporary encompassing direct-acting viral protein inhibitors, host-targeted therapeutic approaches, and emerging non-classical or target‒agnostic interventions.