Targeting the non-structural proteins of hepatitis C virus: beyond hepatitis C virus protease and polymerase
| Autor: | Tod P. Holler, David C. Pryde, Tanya Parkinson |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
NS3
Protease viruses Ribavirin Hepatitis C virus medicine.medical_treatment virus diseases biochemical phenomena metabolism and nutrition Biology medicine.disease_cause medicine.disease Virology digestive system diseases Virus chemistry.chemical_compound chemistry Pegylated interferon Hepatocellular carcinoma Drug Discovery medicine NS5A medicine.drug |
| Zdroj: | Expert Opinion on Drug Discovery. 4:293-314 |
| ISSN: | 1746-045X 1746-0441 |
| DOI: | 10.1517/17460440902762802 |
| Popis: | Chronic hepatitis C virus (HCV) infection is a main cause of cirrhosis of the liver and hepatocellular carcinoma. The standard of care is a combination of pegylated interferon with ribavirin, a regimen that has undesirable side effects and is frequently ineffective. Compounds targeting HCV protease and polymerase are in late-stage clinical trials and have been extensively reviewed elsewhere.To review and evaluate the progress towards finding novel HCV antivirals targeting HCV proteins beyond the already precedented NS3 protease and NS5B polymerase.Searches of CAplus and Medline databases were combined with information from key conferences. This review focuses on NS2/3 serine protease, NS3 helicase activity and the non-structural proteins 4A, 4B and 5A.Use of the replicon model of HCV replication and biochemical assays of specific targets has allowed screening of vast libraries of compounds, but resulted in clinical candidates from only NS4A and NS5A. The field is hindered by a lack of good chemical matter that inhibits the remaining enzymes from HCV, and a lack of understanding of the functions of non-structural proteins 4A, 4B and 5A in the replication of HCV. |
| Databáze: | OpenAIRE |
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