Thiazolides: a new class of antiviral drugs.
ABSTRACT Thiazolides have emerged as a new class of broad-spectrum antiviral drugs, and the first thiazolide, nitazoxanide, is in late-stage clinical trials for treating chronic hepatitis C.
To review the chemistry, pharmacology, toxicology and efficacy of thiazolides as antiviral agents with emphasis on clinical development of nitazoxanide in treating chronic hepatitis C.
Literature search, information from Romark Laboratories and my personal experience with the discovery and development of thiazolides serve as the sources for this review.
Thiazolides are metabolically stable, highly bound to plasma proteins and are associated with a favorable toxicology profile. Phase II clinical trials have demonstrated efficacy and safety of nitazoxanide added to peginterferon with or without ribavirin in treating patients with chronic hepatitis C. More limited clinical data indicated potential in treating chronic hepatitis B, and three randomized controlled trials have demonstrated efficacy in reducing the duration of viral gastroenteritis. New generation thiazolides with the nitro group of nitazoxanide replaced by a non-reducible group are not active against anaerobes but retain broad-spectrum activity against viruses. Further studies are needed. Research indicates that these drugs may play an important and complementary role in combination with other classes of antiviral drugs.
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ABSTRACT: Hepatitis C virus (HCV) causes significant morbidity and mortality worldwide with nearly 3% of the world population infected by this virus. Fortunately, this virus does not establish latency, and hence it may be possible to eradicate it. HCV is strongly associated with liver cirrhosis and hepatocellular carcinoma and is currently treated with pegylated interferon-alpha (peg-IFN-alpha) and ribavirin. Unfortunately, these limited treatment options often produce significant side effects, and currently, complete eradication of virus with combined drug modalities has not yet been achieved for the majority of chronically HCV-infected individuals. Restricted treatment options, lack of a universal cure for HCV and the link between chronic infection, liver cirrhosis and hepatocellular carcinoma necessitate design of novel drugs and treatment options. Understanding the relationship between the immune response, viral clearance and inhibition of viral replication with pharmacology-based design can ultimately allow for complete eradication of HCV. This review focuses upon significant novel preclinical and clinical specifically targeted antiviral therapy (STAT-C) drugs under development, highlights their mechanism of action, and discusses their impact on systemic viral loads and permanent clearance of infection.Journal of Viral Hepatitis 02/2010; 17(2):77-90. · 3.08 Impact Factor
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ABSTRACT: Cryptosporidiosis is a major infection of humans, leading to diarrhoea and growth failure in children, diarrhoea and malnutrition in immunocompromised adults, and is associated with increased mortality in all age groups. Using the country of Zambia as an example, I review the possible approaches to treatment and prevention in a tropical setting. The current optimal therapy for cryptosporidiosis is nitazoxanide which works well in HIV uninfected children, but treatment in patients with HIV infection remains remarkably difficult. No single drug has demonstrated efficacy in a randomised trial. No vaccine is available, so the best option for prevention for the moment is filtration and clean storage of drinking water. This would be expected to reduce cryptosporidiosis dramatically, but this needs to be demonstrated directly. Water filtration would have the added benefit of protection against many other pathogens, but the paucity of alternative approaches highlights the need for a better understanding of this important human pathogen.Parasitology 02/2011; 138(12):1488-91. · 2.36 Impact Factor
- Journal of Medicinal Chemistry 01/2011; 54:4119-4132. · 5.61 Impact Factor