Inhibition of Hepatitis C Virus Replication by Arsenic Trioxide
Journal
Antimicrobial Agents and Chemotherapy
Journal Volume
48
Journal Issue
8
Start Page
2876-2882
ISSN
0066-4804
1098-6596
Date Issued
2004-08
Author(s)
Der-Ren Hwang
Yuan-Chin Tsai
Jin-Ching Lee
Kuo-Kuei Huang
Ren-Kuo Lin
Chia-Hua Ho
Ying-Ting Lin
John T. A. Hsu
Chau-Ting Yeh
Abstract
Hepatitis C virus (HCV) is a serious global problem, and present therapeutics are inadequate to cure HCV infection. In the present study, various antiviral assays show that AS2O3 at submicromolar concentrations is capable of inhibiting HCV replication. The 50% effective concentration (EC50) of AS2O3 required to inhibit HCV replication was 0.35 μM when it was determined by a reporter-based HCV replication assay, and the EC50 was below 0.2 μM when it was determined by quantitative reverse transcription-PCR analysis. As2O3 did not cause cellular toxicity at this concentration, as revealed by an MTS [3-(4,5-dimethylthiozol-2-yl)-5-(3- carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] assay. A combination of AS2O3 and alpha interferon exerted synergistic effects against HCV, as revealed by a multiple linear logistic model and isobologram analysis. Furthermore, in an alternative HCV antiviral system that may recapitulate additional steps involved in HCV infection and replication, AS2O3 at 0.3 μM totally abolished the HCV signal, whereas alpha interferon at a high dose (5,000 IU/ml) only partially suppressed the HCV signal. The study highlights the indications for use of a novel class of anti-HCV agent. Further elucidation of the exact antiviral mechanism of AS2O3 may lead to the development of agents with potent activities against HCV or related viruses.
Publisher
American Society for Microbiology
Type
journal article