Premium
Synthetic lipophilic antioxidant BO‐653 suppresses HCV replication
Author(s) -
Yasui Fumihiko,
Sudoh Masayuki,
Arai Masaaki,
Kohara Michinori
Publication year - 2013
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.23466
Subject(s) - hepatitis c virus , interferon , intracellular , antioxidant , virology , chemistry , viral replication , hela , subgenomic mrna , cell culture , virus , microbiology and biotechnology , biology , rna , cell , biochemistry , gene , genetics
The influence of the intracellular redox state on the hepatitis C virus (HCV) life cycle is poorly understood. This study demonstrated the anti‐HCV activity of 2,3‐dihydro‐5‐hydroxy‐2,2‐dipentyl‐4,6‐di‐ tert ‐butylbenzofuran (BO‐653), a synthetic lipophilic antioxidant, and examined whether BO‐653's antioxidant activity is integral to its anti‐HCV activity. The anti‐HCV activity of BO‐653 was investigated in HuH‐7 cells bearing an HCV subgenomic replicon (FLR3‐1 cells) and in HuH‐7 cells infected persistently with HCV (RMT‐tri cells). BO‐653 inhibition of HCV replication was also compared with that of several hydrophilic and lipophilic antioxidants. BO‐653 suppressed HCV replication in FLR3‐1 and RMT‐tri cells in a concentration‐dependent manner. The lipophilic antioxidants had stronger anti‐HCV activities than the hydrophilic antioxidants, and BO‐653 displayed the strongest anti‐HCV activity of all the antioxidants examined. Therefore, the anti‐HCV activity of BO‐653 was examined in chimeric mice harboring human hepatocytes infected with HCV. The combination treatment of BO‐653 and polyethylene glycol‐conjugated interferon‐α (PEG‐IFN) decreased serum HCV RNA titer more than that seen with PEG‐IFN alone. These findings suggest that both the lipophilic property and the antioxidant activity of BO‐653 play an important role in the inhibition of HCV replication. J. Med. Virol. 85:241–249, 2013. © 2012 Wiley Periodicals, Inc.