標題: Inhibition of hepatitis C virus replication by antimonial compounds
作者: Hwang, DR
Lin, RK
Leu, GZ
Lin, TY
Lien, TW
Yu, MC
Yeh, CT
Hsu, JTA
生物科技學系
Department of Biological Science and Technology
公開日期: 1-十月-2005
摘要: Chronic hepatitis C virus (HCV) infection is a worldwide health problem causing serious complications, such as liver cirrhosis and hepatoma. Alpha interferon (IFN-alpha) 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 mu M of Sb) in the HCV subgenomic-replicon system. We also found that SSG and IFN-alpha 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-alpha could sustain the antiviral response better than SSG or IFN-alpha alone. The results suggest that SSG may be a good drug candidate for use in combination with other therapeutics, such as IFN-alpha and ribavirin, to treat HCV infection.
URI: http://dx.doi.org/10.1128/AAC.49.10.4197-4202.2005
http://hdl.handle.net/11536/13188
ISSN: 0066-4804
DOI: 10.1128/AAC.49.10.4197-4202.2005
期刊: ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume: 49
Issue: 10
起始頁: 4197
結束頁: 4202
顯示於類別:期刊論文


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