Synthetic lipophilic antioxidant BO-653 suppresses HCV replication

• Published in: Journal of medical virology 2013-02, Vol.85 (2), p.241-249
• Main Authors: Yasui, Fumihiko, Sudoh, Masayuki, Arai, Masaaki, Kohara, Michinori
• Format: Article
• Language: English
• Subjects: Animals; antioxidant activity; Antioxidants; Antioxidants - administration & dosage; Antioxidants - pharmacology; Antiviral Agents - administration & dosage; Antiviral Agents - pharmacology; Benzofurans - administration & dosage; Benzofurans - pharmacology; Biological and medical sciences; BO-653; Cell Line; chemical structure; chimeric mice; Disease Models, Animal; Drug Therapy, Combination - methods; Fundamental and applied biological sciences. Psychology; HCV replication; Hepacivirus - drug effects; Hepacivirus - physiology; Hepatitis; Hepatitis C - drug therapy; Hepatitis C virus; Hepatocytes - virology; Human viral diseases; Humans; Infectious diseases; Interferon-alpha - administration & dosage; Medical sciences; Mice; Microbiology; Miscellaneous; RNA, Viral - blood; Treatment Outcome; Viral diseases; Viral Load; Virology; Virus Replication - drug effects
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/jmv.23466

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.