Evaluating anti-viral effect of Ivermectin on porcine epidemic diarrhea virus and analyzing the related genes and signaling pathway by RNA-seq in vitro

Porcine epidemic diarrhea virus (PEDV) has catastrophic impacts on the global pig industry. However, there remains no effective drugs for PEDV infection. Ivermectin is an FDA-approved anthelmintic drug used to treat worm infections. In this study, we reported the broad-spectrum antiviral activity of Ivermectin in vitro. Ivermectin can inhibit PEDV infections of different genotypes. Avermectin derivatives can also inhibit PEDV infections. A time of addition assay showed that Ivermectin exhibited potent anti-PEDV activity when added simultaneously with or post virus infection. Furthermore, Ivermectin significantly inhibited the late stage of viral infection by affecting viral release. RNA sequencing indicates Ivermectin induces cell cycle arrest, which may be related to its ability to inhibit viral release. Interestingly, when combined with Niclosamide, Ivermectin demonstrated an enhanced anti-PEDV effect. These findings highlight Ivermectin as a novel antiviral agent with potential for the development of drugs against PEDV infection.