Saikosaponin C as an antiviral agent inhibits the largemouth bass ranavirus in vitro and in vivo

Abstract

Largemouth bass ranavirus (LMBRaV) is a highly lethal virus that has devastated the largemouth bass aquaculture sector. Therefore, it is imperative to develop therapeutic strategies for the control of this pathogen. In this work, the antiviral activity of Saikosaponin C was examined both in vitro and in vivo. According to the results of the in vitro antiviral activity assay, 30 mg/L of Saikosaponin C significantly down-regulated the expression of the LMBRaV major coat protein (MCP) gene in epithelioma papilloma cyprinid (EPC) cells, with an inhibitory rate exceeding 84%, and prevented LMBRaV replication in a dose-dependent manner. It also significantly limited its cytopathic effect (CPE), thereby playing a protective role on infected cells. Notably, Saikosaponin C has a certain preventative impact on the virus by influencing the mechanisms by which viral particles connect to cell receptors, which prevents LMBRaV from adsorbing on EPC cells. Simultaneously, Saikosaponin C also directly inactivated LMBRaV. The results of exploring the viral invasion cycle demonstrated that Saikosaponin C primarily exerted its antiviral effect during the middle stage (2–6 h) of viral infection. In addition, Saikosaponin C inhibited LMBRaV-induced apoptosis of EPC cells, maintained physiological cellular morphology and structure, and protected cells from loss of cellular morphology, formation of apoptotic vesicles, and cell fragmentation. Moreover, Saikosaponin C considerably improved the survival of virus-infected largemouth bass, according to the findings of in vivo investigations. In summary, Saikosaponin C demonstrated excellent anti-LMBRaV activity and holds considerable promise for development in the field of aquaculture.