Abstract
Chronic infection with hepatitis C virus (HCV) remains a global health concern. Using both in vitro and cellbased assays, a series of small molecule agents specific for the viral RNA-dependent RNA polymerase have been shown to interfere with viral RNA replication. Although no agents targeting this viral enzyme have demonstrated sustained efficacy in infected patients as measured by reduction in viral load at 72 weeks post-treatment, proof-of-concept has been achieved in the clinic. A comprehensive account of the structure-activity relationship for nucleoside and non-nucleoside inhibitors of HCV polymerase, as well as consideration of early discovery biologic approaches targeting NS5B are reviewed.
Keywords: Nonstructural protein 5B (NS5B), RNA-dependent RNA polymerase (RdRp), hepatitis C virus (HCV), nonnucleoside inhibitors (NNI), nucleoside inhibitors, acyl pyrrolidine, benzofuran
Mini-Reviews in Medicinal Chemistry
Title: Small Molecule and Biologic Inhibitors of Hepatitis C Virus: A Symbiotic Approach
Volume: 6 Issue: 11
Author(s): A. M. Del Vecchio and R. T. Sarisky
Affiliation:
Keywords: Nonstructural protein 5B (NS5B), RNA-dependent RNA polymerase (RdRp), hepatitis C virus (HCV), nonnucleoside inhibitors (NNI), nucleoside inhibitors, acyl pyrrolidine, benzofuran
Abstract: Chronic infection with hepatitis C virus (HCV) remains a global health concern. Using both in vitro and cellbased assays, a series of small molecule agents specific for the viral RNA-dependent RNA polymerase have been shown to interfere with viral RNA replication. Although no agents targeting this viral enzyme have demonstrated sustained efficacy in infected patients as measured by reduction in viral load at 72 weeks post-treatment, proof-of-concept has been achieved in the clinic. A comprehensive account of the structure-activity relationship for nucleoside and non-nucleoside inhibitors of HCV polymerase, as well as consideration of early discovery biologic approaches targeting NS5B are reviewed.
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Del Vecchio M. A. and Sarisky T. R., Small Molecule and Biologic Inhibitors of Hepatitis C Virus: A Symbiotic Approach, Mini-Reviews in Medicinal Chemistry 2006; 6 (11) . https://dx.doi.org/10.2174/138955706778742786
DOI https://dx.doi.org/10.2174/138955706778742786 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
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