Ellagic acid inhibits bovine rotavirus in vitro and in vivo

Abstract Bovine rotavirus (BRV) causes neonatal diarrhea in calves, which leads to high mortality and economic losses globally and poses a risk for zoonotic transmission. There are no currently available effective antiviral drugs for managing BRV infections. This study aimed to evaluate the antiviral efficacy of ellagic acid against BRV in vitro and in vivo and to elucidate its underlying mechanisms of action. The findings revealed that ellagic acid significantly inhibited BRV replication in a dose-dependent manner in MA-104 cells by suppressing RNA synthesis, protein expression, and progeny virion production ( P < 0.001 ). In addition, ellagic acid alleviated the intestinal pathogenic effects of BRV infection in newborn Kunming mice and reduced the viral load in vivo. Transcriptomic analysis revealed that ellagic acid selectively regulated 115 differentially expressed genes (DEGs) ( P < 0.05 ); the main enriched and relevant pathways were the PPAR signaling pathway, thyroid hormone synthesis, salivary secretion, and the insulin secretion signaling pathway. Importantly, 44 DEGs, including Akp3 , St6galnac1 , and Gal3st2 , were restored after ellagic acid treatment, indicating modulation of the host response to BRV infection. Overall, ellagic acid demonstrated significant antiviral activity against BRV both in vitro and in vivo, highlighting its potential as a candidate treatment for BRV infection.