Inhibitory Effects of Enoxolone on Porcine Epidemic Diarrhea Virus In Vitro and In Vivo

Porcine epidemic diarrhea (PED) is characterized as an acute and highly contagious intestinal ailment induced by the PED virus (PEDV), presenting clinical symptoms such as emesis, diarrhea, and dehydration. The occurrence of PED has imposed a substantial economic burden on the global swine farming industry. The PEDV strain exhibits a proclivity for mutations, and the immune response elicited by traditional vaccines may prove ineffective against the virus. Meanwhile, given concerns about the tolerance to existing drugs. Consequently, there is an urgent necessity to develop novel anti PEDV drugs. As a natural compound, studies have demonstrated that enoxolone possesses multiple pharmacological attributes, encompassing antitumor, antiulcer, antiviral, and anti-inflammatory activities both in vivo and in vitro. In this study, we investigated the antiviral efficacy of enoxolone against PEDV. Enoxolone inhibits the proliferation of PEDV through multiple pathways. Initially, it degrades the nucleocapsid (N) protein via the lysosomal-autophagy pathway. Additionally, in vitro experiments have demonstrated that Enoxolone suppresses the NF-κB signaling pathway activated by PEDV, indicating its anti-inflammatory properties and its ability to inhibit the inflammatory response triggered by PEDV in vitro. Furthermore, in vivo results show that enoxolone effectively alleviates the symptoms and intestinal damage caused by PEDV in piglets. Briefly speaking, our research verifies that enoxolone can inhibit the replication of PEDV both in vivo and in vitro, providing a novel direction for the development of antiviral drugs against PED.