Abstract
The human and monetary costs of chronic hepatitis C and the complications arising from this disease emphasize the urgency to find a treatment for Hepatitis C Virus (HCV) infected patients. The current standard of treatment for patients chronically infected with HCV is combination therapy with pegylated interferon plus ribavirin. Recently, viral enzymes have become the target of efforts to develop small molecule inhibitors interfering with the essential steps in the life cycle of the virus. Amongst these enzymes the HCV-encoded NS5B RNA-dependent RNA polymerase (NS5B RdRp) is essential for viral replication and has been recognized as a prime target for therapeutic intervention. Several distinct classes of inhibitors of NS5B RdRp have been disclosed in the literature, including active site inhibitors such as nucleosides and pyrophosphate mimetics, as well as non-nucleoside inhibitors. The latter, based on the success of allosteric inhibitors in the treatment of HIV infection, have been developed into compounds which show activity in the subgenomic cell-culture assay of HCV replication. This review provides an account of the recent developments in this field.
Keywords: Allosteric inhibition, Hepatitis C virus, RNA polymerase, sub-genomic replicon
Infectious Disorders - Drug Targets
Title: Allosteric Inhibition of the Hepatitis C Virus NS5B RNA Dependent RNA Polymerase
Volume: 6 Issue: 1
Author(s): Uwe Koch and Frank Narjes
Affiliation:
Keywords: Allosteric inhibition, Hepatitis C virus, RNA polymerase, sub-genomic replicon
Abstract: The human and monetary costs of chronic hepatitis C and the complications arising from this disease emphasize the urgency to find a treatment for Hepatitis C Virus (HCV) infected patients. The current standard of treatment for patients chronically infected with HCV is combination therapy with pegylated interferon plus ribavirin. Recently, viral enzymes have become the target of efforts to develop small molecule inhibitors interfering with the essential steps in the life cycle of the virus. Amongst these enzymes the HCV-encoded NS5B RNA-dependent RNA polymerase (NS5B RdRp) is essential for viral replication and has been recognized as a prime target for therapeutic intervention. Several distinct classes of inhibitors of NS5B RdRp have been disclosed in the literature, including active site inhibitors such as nucleosides and pyrophosphate mimetics, as well as non-nucleoside inhibitors. The latter, based on the success of allosteric inhibitors in the treatment of HIV infection, have been developed into compounds which show activity in the subgenomic cell-culture assay of HCV replication. This review provides an account of the recent developments in this field.
Export Options
About this article
Cite this article as:
Koch Uwe and Narjes Frank, Allosteric Inhibition of the Hepatitis C Virus NS5B RNA Dependent RNA Polymerase, Infectious Disorders - Drug Targets 2006; 6 (1) . https://dx.doi.org/10.2174/187152606776056724
DOI https://dx.doi.org/10.2174/187152606776056724 |
Print ISSN 1871-5265 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-3989 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
TNF-α Inhibitors with Anti-Oxidative Stress Activity from Natural Products
Current Topics in Medicinal Chemistry Designed Ankyrin Repeat Proteins: A Look at their Evolving Use in Medicine with a Focus on the Treatment of Chorioretinal Vascular Disorders
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Knockdown of C-C Chemokine Receptor 5 (CCR5) is Protective Against Cerebral Ischemia and Reperfusion Injury
Current Neurovascular Research Antidiabetic Drugs: Mechanisms of Action and Potential Outcomes on Cellular Metabolism
Current Pharmaceutical Design Genetics and Genomics of Hepatic Acute Phase Reactants: A Mini-Review
Inflammation & Allergy - Drug Targets (Discontinued) Dual Cyclooxygenase and Carbonic Anhydrase Inhibition by Nonsteroidal Anti-Inflammatory Drugs for the Treatment of Cancer
Current Medicinal Chemistry The Role of Nutrition During the COVID-19 Pandemic: What We Know
Endocrine, Metabolic & Immune Disorders - Drug Targets Pharmacological Treatment of Cognitive Symptoms in Major Depressive Disorder
CNS & Neurological Disorders - Drug Targets Regulation of P2X3 Receptor Structure and Function
CNS & Neurological Disorders - Drug Targets Application of RNA Interference for the Control of Female Reproductive Functions
Current Pharmaceutical Design Cytotoxic and Apoptotic Effect of <i>Iris taochia</i> Plant Extracts on Human Breast Cancer (MCF-7) Cells
Current Proteomics Neuroprotection for Amyotrophic Lateral Sclerosis: Role of Stem Cells, Growth Factors, and Gene Therapy
Central Nervous System Agents in Medicinal Chemistry Advances in Lipid-Based Subunit Vaccine Formulations
Current Immunology Reviews (Discontinued) Cancer/Testis Antigens Trigger Epithelial-Mesenchymal Transition and Genesis of Cancer Stem-Like Cells
Current Pharmaceutical Design TNF Receptor: Fc Fusion Protein Downregulates RANKL/OPG Ratio by Inhibiting CXCL16/CXCR6 in Active Ankylosing Spondylitis
Current Pharmaceutical Biotechnology Endocannabinoids and their Involvement in the Neurovascular System
Current Neurovascular Research The Endocannabinoid System and Schizophrenia: Integration of Evidence
Current Pharmaceutical Design Laboratory Assessment of Patients with Suspected Rheumatic Musculoskeletal Diseases: Challenges and Pitfalls
Current Rheumatology Reviews Genetics of Chronic Obstructive Pulmonary Disease
Current Respiratory Medicine Reviews Glycosylated Antitumor Ether Lipids: Activity and Mechanism of Action
Anti-Cancer Agents in Medicinal Chemistry