ERAD inhibitor Eeyarestatin I (EerI) suppresses duck plague virus by restoring STING-mediated antiviral immunity

Duck plague (DP), caused by the duck plague virus (DPV), is a highly contagious disease characterized by high morbidity and mortality, causing significant economic losses and biosecurity risks to the duck farming industry. Since current vaccines do not provide complete protection, the development of antiviral drugs is urgently needed. In this study, we evaluated the anti-DPV activity of the ER-associated degradation (ERAD) pathway inhibitor Eeyarestatin I (EerI) in vitro. Our results demonstrated that EerI suppressed DPV proliferation in duck embryo fibroblast (DEF) cells in a dose-dependent manner, with the antiviral effect persisting for over 96 hours. Further investigation revealed that EerI inhibits viral genome replication and cell-to-cell spread, thereby exerting a therapeutic antiviral effect. Mechanistically, DPV infection activates endoplasmic reticulum stress (ERS) and the ERAD pathway, promoting the degradation of STING via ERAD to suppress antiviral immunity. EerI counteracts this process by blocking the ERAD pathway, thereby restoring STING stability and function and ultimately inhibiting DPV infection. In conclusion, EerI is a candidate antiviral agent against DPV.