Zn²⁺ inhibits PEDV replication by inducing autophagy through the Akt-mTOR pathway

Porcine epidemic diarrhea virus (PEDV) is a coronavirus that induces diarrhea in pigs, leading to severe economic losses in the global pig industry. Currently, effective antiviral treatments for porcine epidemic diarrhea (PED) are rarely available for clinical use. Zinc (Zn²⁺), an essential mineral, is known to reduce diarrhea in piglets transitioning from milk to solid feed by modulating immune system activity. In this study, the role of Zn²⁺ in regulating PEDV infection was investigated to explore its potential for reducing diarrhea. Our findings show that Zn²⁺ inhibits PEDV replication in Vero-E6 cells by inducing autophagy. Notably, we demonstrated that autophagy negatively regulates PEDV infection, as confirmed by the use of autophagy inhibitor (3-MA) and activator (RAPA). Further analysis revealed that PEDV infection activates the Akt-mTOR signaling pathway, while Zn²⁺ inhibits this pathway in Vero-E6 cells. Additionally, overexpression of Akt and Akt_Ser473 plasmids in Vero-E6 cells highlights the role of Akt phosphorylation in the Zn²⁺ induced autophagy that inhibits PEDV replication. In summary, this study identifies a mechanism by which Zn²⁺ suppresses PEDV infection through the Akt-mTOR pathway by mediating autophagy. These findings provide valuable insights into the potential use of Zn²⁺ as an effective antiviral agent in vivo.