Antiviral mechanism of glycyrrhizic acid against BVDV: suppression of viral replication and immune regulation

Introduction Bovine viral diarrhea virus (BVDV), a globally prevalent pathogen in cattle, causes severe economic losses through acute diarrhea, immunosuppression, and reproductive failure, with mortality rates reaching 20%–30% in persistently infected herds. This study investigated glycyrrhizic acid (GA), a bioactive triterpenoid glycoside derived from licorice root with known anti-inflammatory and broad-spectrum antiviral properties, as a potential inhibitor of BVDV replication. Methods Using in vitro (MDBK cells) and in vivo (BALB/c mice) models, we evaluated the antiviral and immunomodulatory effects of GA. Cells were treated with 10 μM GA, and mice received 20 mg/kg/day GA. Viral replication, cytokine expression, hepatic histopathology, and gut microbiota were assessed. Results GA treatment significantly reduced BVDV replication, decreasing 5’UTR and NS5B mRNA expression by >80% ( P < 0.01) and viral titers by 2.3-log in liver tissue. GA concurrently modulated host immune responses, suppressing pro-inflammatory cytokines (TNF-α by 68%, IL-6 by 54%) while elevating IL-10 (2.1-fold), and substantially improved hepatic histopathology scores ( P < 0.05 versus infected controls). ELISA revealed GA-mediated downregulation of IFN-β during infection. Analysis of gut microbiota at 7 days post-infection revealed that both GA and ribavirin (RBV) treatments modulated microbial community structure, with RBV showing profiles more closely resembling uninfected controls. Discussion These findings establish GA’s dual antiviral mechanism—direct suppression of viral RNA synthesis and immunomodulation—positioning this natural compound as a promising therapeutic candidate against BVDV infection in livestock.