Abstract
Equid alphaherpesvirus type 8 (EHV-8) is a contagious pathogen that causes reproductive disorders, respiratory diseases, and viral encephalitis in equids, resulting in significant economic losses for the global horse and donkey industries. Currently, there are no approved antiviral drugs or vaccines available for EHV-8 control. In this study, we investigated the antiviral efficacy of celastrol against EHV-8 both in vitro and in vivo. Our results demonstrated that celastrol significantly inhibited EHV-8 infection in Rabbit kidney (RK-13) and equine dermal cells (NBL-6) in a dose-dependent manner. Mechanistic studies revealed that celastrol interfered with viral replication at multiple stages of the infection cycle. Furthermore, we found that celastrol induced an antiviral interferon response through activation of the Nrf2/HO-1 signaling pathway. Importantly, celastrol treatment significantly reduced EHV-8 replication and ameliorated lung pathology in a mouse model. These findings suggest that celastrol may represent a promising therapeutic agent for the treatment of EHV-8 infections.