L-2-aminoadipic acid inhibits porcine epidemic diarrhea virus replication by targeting and reducing cellular...

Porcine epidemic diarrhea caused by porcine epidemic diarrhea virus (PEDV) is an acute and highly contagious intestinal infectious disease. The metabolic alterations during PEDV infection remain largely unexplored. In this study, LLC-PK1 cells infected with PEDV were subjected to non-targeted metabolomics analysis. Notably, the amino acid metabolite L-2-aminoadipic acid (L-2AA) was significantly upregulated, while indole-3-acetic acid (3-IAA) exhibited a marked downregulation following PEDV infection. Subsequent investigations revealed that both L-2AA and 3-IAA significantly hindered the late stage of viral propagation. Mechanistically, aldehyde dehydrogenase 7A1 (ALDH7A1), a key enzyme involved in the biosynthesis of L-2AA, mediates the PEDV-induced upregulation of L-2AA and functions to negatively regulate viral replication. Detailed analysis indicated that L-2AA mitigates PEDV infection via reducing autophagic activity. These data support a novel mechanism used by L-2AA to downregulate autophagic activity to block viral replication and provide potential anti-PEDV drug targets.