Epigallocatechin Gallate (EGCG) Inhibits African Swine Fever Virus Replication by Targeting Key Viral Proteins and Regulating Host Lipid Metabolism.

AbstractAfrican swine fever (ASF) is a highly pathogenic swine infectious disease caused by African swine fever virus (ASFV), with a mortality rate approaching 100% in domestic pigs and causing severe economic losses to the global pig industry. Despite the recent approval of live-attenuated ASF vaccines in limited regions such as Vietnam, universally safe, globally authorized commercial vaccines and effective antiviral therapeutics remain unavailable, creating an urgent demand for innovative anti-ASFV intervention strategies. In this study, epigallocatechin gallate (EGCG) was identified to exert prominent inhibitory effects on ASFV proliferation in vitro. Viral life cycle assays indicated that EGCG mainly targets the internalization and post-entry genome replication stages. Molecular docking combined with bio-layer interferometry (BLI) confirmed high-affinity direct binding between EGCG and two indispensable ASFV proteins, p72 and p1192R. Furthermore, EGCG dose-dependently activates the AMP-activated protein kinase (AMPK) signaling pathway, downregulates lipid synthesis-related genes, and reverses ASFV-induced lipid droplet accumulation and abnormal increases in total cholesterol (TC), triglycerides (TG), and free fatty acids (FFAs), thereby disrupting the lipid metabolic microenvironment required for viral replication. Collectively, EGCG suppresses ASFV replication through dual mechanisms: targeting key viral proteins and regulating host lipid metabolism. This study highlights EGCG as a promising anti-ASFV candidate and offers a novel theoretical basis for the development of anti-ASFV agents.