title: Antiviral activity of glycyrrhizin against hepatitis C virus in vitro.
abstract: Glycyrrhizin (GL) has been used in Japan to treat patients with chronic viral hepatitis, as an anti-inflammatory drug to reduce serum alanine aminotransferase levels. GL is also known to exhibit various biological activities, including anti-viral effects, but the anti-hepatitis C virus (HCV) effect of GL remains to be clarified. In this study, we demonstrated that GL treatment of HCV-infected Huh7 cells caused a reduction of infectious HCV production using cell culture-produced HCV (HCVcc). To determine the target step in the HCV lifecycle of GL, we used HCV pseudoparticles (HCVpp), replicon, and HCVcc systems. Significant suppressions of viral entry and replication steps were not observed. Interestingly, extracellular infectivity was decreased, and intracellular infectivity was increased. By immunofluorescence and electron microscopic analysis of GL treated cells, HCV core antigens and electron-dense particles had accumulated on endoplasmic reticulum attached to lipid droplet (LD), respectively, which is thought to act as platforms for HCV assembly. Furthermore, the amount of HCV core antigen in LD fraction increased. Taken together, these results suggest that GL inhibits release of infectious HCV particles. GL is known to have an inhibitory effect on phospholipase A2 (PLA2). We found that group 1B PLA2 (PLA2G1B) inhibitor also decreased HCV release, suggesting that suppression of virus release by GL treatment may be due to its inhibitory effect on PLA2G1B. Finally, we demonstrated that combination treatment with GL augmented IFN-induced reduction of virus in the HCVcc system. GL is identified as a novel anti-HCV agent that targets infectious virus particle release.
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Matsuura
authors.forename: Haruyo
authors.initials: H
authors.lastname: Aoyagi
authors.forename: Mami
authors.initials: M
authors.lastname: Matsuda
authors.forename: Su Su
authors.initials: SS
authors.lastname: Hmwe
authors.forename: Tomoko
authors.initials: T
authors.lastname: Date
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Watanabe
authors.forename: Koichi
authors.initials: K
authors.lastname: Watashi
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Suzuki
authors.forename: Shizuko
authors.initials: S
authors.lastname: Ichinose
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Wake
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Suzuki
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Miyamura
authors.forename: Takaji
authors.initials: T
authors.lastname: Wakita
authors.forename: Hideki
authors.initials: H
authors.lastname: Aizaki
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002460:Cell Line; D018274:Electroporation; D004721:Endoplasmic Reticulum / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D054500:Group IB Phospholipases A2 / Q000378:metabolism; D016174:Hepacivirus / Q000187:drug effects*; D006801:Humans; D046529:Microscopy, Electron, Transmission; D034622:RNA Interference; D053586:Virus Internalization / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D019695:Glycyrrhizic Acid; D054500:Group IB Phospholipases A2; C516202:PLA2G1B protein, human