This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Hwang, D.-R. Articles by Hsu, J. T.-A. Search for Related Content PubMed PubMed Citation Articles by Hwang, D.-R. Articles by Hsu, J. T.-A.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, October 2005, p. 4197-4202, Vol. 49, No. 10
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.10.4197-4202.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Inhibition of Hepatitis C Virus Replication by Antimonial Compounds

Der-Ren Hwang ,^1,, Ren-Kuo Lin,^1, Guang-Zhou Leu,^2, Tiao-Yin Lin,² Tzu-Wen Lien,¹ Ming-Chen Yu,¹ Chau-Ting Yeh,³ and John T.-A. Hsu^1,4*

Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, Taiwan, Republic of China,¹ Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan, Republic of China,² Liver Research Unit, Chang Gung Memorial Hospital, Taipei, Taiwan, Republic of China,³ Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan, Republic of China⁴

Received 13 September 2004/ Returned for modification 8 November 2004/ Accepted 25 April 2005

Chronic hepatitis C virus (HCV) infection is a worldwide health problem causing serious complications, such as liver cirrhosis and hepatoma. Alpha interferon (IFN-) or its polyethylene glycol-modified form combined with ribavirin is the only recommended therapy. However, an alternative therapy is needed due to the unsatisfactory cure rate of the IFN-based therapy. Using a modified reporter assay based on the HCV subgenomic-replicon system, we found that sodium stibogluconate (SSG), a compound used for leishmania treatment, suppressed HCV replication. We have previously reported that SSG is effective at inhibiting HCV replication in a cell line permissive for HCV infection/replication and in an ex vivo assay using fresh human liver slices obtained from patients infected with HCV (26). In this study, we show that the SSG 50% inhibitory dose for HCV replication is 0.2 to 0.3 mg/ml (equivalent to 345 to 517 µM of Sb) in the HCV subgenomic-replicon system. We also found that SSG and IFN- exert a strong synergistic anti-HCV effect in both the traditional isobologram analysis and the median effect principle (CalcuSyn analysis). The combination of SSG and IFN- could sustain the antiviral response better than SSG or IFN- alone. The results suggest that SSG may be a good drug candidate for use in combination with other therapeutics, such as IFN- and ribavirin, to treat HCV infection.

D.-R.H., R.-K.L., and G.-Z.L. contributed equally to this study.

Present address: The Scripps Research Institutes (TSRI), 10550 Torrey Pines Road, La Jolla, CA 92037.