Ginsenoside Rh1 Suppresses Vesicular Stomatitis Virus Replication by Inhibiting Autophagy to Promote Immune Responses

Vesicular stomatitis virus (VSV), a member of the Vesiculovirus genus within the Rhabdoviridae family, is a widespread pathogen affecting all hoofed livestock species, leading to reduced animal growth and productivity. To date, no effective therapeutic treatment for VSV infection has been developed. Natural medicinal compounds with immunomodulatory properties represent a promising supportive strategy for infection control. Ginsenoside Rh1, a primary bioactive component of ginseng plants, has been reported to possess broad pharmacological and immunoregulatory activities. Nevertheless, its potential antiviral effects against VSV remain unexplored. In this study, we demonstrate that Ginsenoside Rh1 exhibits considerable antiviral activity against VSV in cellular models. Mechanistically, its antiviral effect is primarily mediated through the inhibition of VSV-induced autophagy, thereby enhancing interferon-mediated antiviral responses. Collectively, our findings identify Ginsenoside Rh1 as a novel antiviral agent active against VSV and potentially related vesiculoviruses, clarify its mechanism of action, and highlight an autophagy-dependent immunomodulatory approach that could be critical for confronting existing and emerging RNA viral infections.