In vitro and in vivo evaluation of the antiviral activity of arctigenin, ribavirin, and ivermectin against viral hemorrhagic septicemia virus infection

Viral hemorrhagic septicemia virus (VHSV) causes a severe and often lethal infection in olive flounder (Para-lichthys olivaceus) in Korea, resulting in mass mortality and substantial economic loss. As a potential prevention strategy for infectious viral diseases, this study aimed to evaluate the antiviral activity of three compounds (arctigenin [ARG], ribavirin [RBV], and ivermectin [IVM]) against VHSV infection in vitro and in vivo. In epithelioma papulosum cyprini cells, the expression of both VHSV glycoprotein (G) and nucleoprotein (N) genes were significantly suppressed by the three compounds in a dose-dependent manner (P < 0.05). Also, cell morphology and viability were maintained at the following concentrations: ARG 1.5 mg/L, RBV 2.5 mg/L, and IVM 10 mg/L. The fish that were treated with RBV (8.33 mg/kg) and IVM (0.25 mg/kg) before VHSV infection and those treated with IVM (0.25 mg/kg) after VHSV infection showed significant improvements in the survival rate, a reduction in the viral shedding rate, and downregulation of viral gene expression compared to those seen in fish with naive VHSV infections. Furthermore, among the innate immune genes studied, persistent expression of Mx and upregulation of tumor necrosis factor-alpha gene expression in VHSV-infected fish treated with RBV and IVM revealed that these compounds might induce an immunostimulatory effect as one of their antiviral activities. Overall, this study supports the use of RBV and IVM as antiviral agents to control VHSV infections in olive flounder.

Automated summary

This study evaluated the antiviral activity of three compounds against VHSV infection in olive flounder. The results showed that the compounds significantly suppressed the expression of VHSV genes and maintained cell morphology and viability. Treatment with the compounds improved survival rate and reduced viral shedding in VHSV-infected fish, indicating their potential as antiviral agents.