Nitazoxanide, tizoxanide and other thiazolides are potent inhibitors of hepatitis B virus and hepatitis C virus replication

Nitazoxanide (NTZ), a thiazolide anti-infective, is active against anaerobic bacteria, protozoa, and a range of viruses in cell culture models, and is currently in phase II clinical development for treating chronic hepatitis C. In this report, we characterize the activities of NTZ and its active met...

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Bibliographic Details
Published in:Antiviral research 2008, Vol.77 (1), p.56-63
Main Authors: Korba, Brent E., Montero, Abigail B., Farrar, Kristine, Gaye, Karen, Mukerjee, Sampa, Ayers, Marc S., Rossignol, Jean-François
Format: Article
Language:English
Subjects:
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antiviral agents
Antiviral Agents - metabolism
Antiviral Agents - pharmacology
Antiviral therapy
Biological and medical sciences
Cell Line
Drug Resistance, Viral
Hepacivirus - drug effects
Hepacivirus - genetics
Hepacivirus - physiology
Hepatitis Antigens - metabolism
Hepatitis B virus
Hepatitis B virus - drug effects
Hepatitis B virus - genetics
Hepatitis B virus - physiology
Hepatitis C virus
Humans
Medical sciences
Mutation
Nitazoxanide
Pharmacology. Drug treatments
Serum
Thiazoles - metabolism
Thiazoles - pharmacology
Thiazolides
Virus Replication - drug effects
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Summary:Nitazoxanide (NTZ), a thiazolide anti-infective, is active against anaerobic bacteria, protozoa, and a range of viruses in cell culture models, and is currently in phase II clinical development for treating chronic hepatitis C. In this report, we characterize the activities of NTZ and its active metabolite, tizoxanide (TIZ), along with other thiazolides against hepatitis B virus (HBV) and hepatitis C virus (HCV) replication in standard antiviral assays. NTZ and TIZ exhibited potent inhibition of both HBV and HCV replication. NTZ was equally effective at inhibiting replication of lamivudine (LMV) and adefovir dipovoxil (ADV)-resistant HBV mutants and against 2′-C-methyl cytidine (2′CmeC) and telaprevir (VX-950)-resistant HCV mutants. NTZ displayed synergistic interactions with LMV or ADV against HBV, and with recombinant interferon alpha-2b (IFN) or 2′CmeC against HCV. Pre-treatment of HCV replicon-containing cells with NTZ potentiated the effect of subsequent treatment with NTZ plus IFN, but not NTZ plus 2′CmeC. NTZ induced reductions in several HBV proteins (HBsAg, HBeAg, HBcAg) produced by 2.2.15 cells, but did not affect HBV RNA transcription. NTZ, TIZ, and other thiazolides are promising new antiviral agents that may enhance current or future anti-hepatitis therapies.
ISSN:0166-3542
1872-9096
DOI:10.1016/j.antiviral.2007.08.005