18 -glycyrrhetinic acid inhibits rotavirus replication in culture

Abstract

Background: Glycyrrhizin (GA) and primary metabolite 18Á- glycyrrhetinic acid (GRA) are pharmacologically active components of the medicinal licorice root, and both have been shown to have antiviral and immunomodulatory properties. Although these properties are well established, the mechanisms of action are not completely understood. In this study, GA and GRA were tested for the ability to inhibit rotavirus replication in cell culture, toward a long term goal of discovering natural compounds that may complement existing vaccines. Methods: Epithelial cells were treated with GA or GRA various times pre- or post-infection and virus yields were easured by immunofluorescent focus assay. Levels of viral proteins VP2, VP6, and NSP2 in GRA treated cells weremeasured by immunoblot to determine if there was an effect of GRA treatment on the accumulation of viral protein. Results: GRA treatment reduced rotavirus yields by 99% when added to infected cultures post- virus adsorption, whereas virus yields in GA treated cultures were similar to mock treated controls. Time of addition experiments indicated that GRA-mediated replication inhibition likely occurs at a step or steps subsequent to virus entry. The amounts of VP2, VP6 and NSP2 were substantially reduced when GRA was added to cultures up to two hours postentry. Conclusions: GRA, but not GA, has significant antiviral activity against rotavirus replication in vitro, and studies to determine whether GRA attenuates rotavirus replication in vivo are underway. © 2012 Hardy et al.; licensee BioMed Central Ltd.