Candidate targets for hepatitis C virus-specific antiviral therapy.
The hepatitis C virus (HCV) was identified as the major causative agent of posttransfusion and community-acquired non-A, non-B hepatitis throughout the world. It is an enveloped virus with a plus-strand RNA genome encoding a polyprotein of about 3,010 amino acids. This polyprotein is cleaved co- and posttranslationally into mature viral proteins by host cell signal peptidases and 2 viral enzymes designated the NS2-3 proteinase and the NS3/4A proteinase complex. It is assumed that virus replication takes place in a membrane-associated complex containing at least 2 viral enzymatic activities: the NS3 nucleoside triphosphatase (NTPase)/helicase and the NS5B RNA-dependent RNA polymerase (RdRp). Based on their important role for the viral life cycle and the wealth of information available for related cellular and viral proteins, the NS3/4A serine-type proteinase complex, the NS3 NTPase/helicase and the NS5B RdRp are the most attractive targets for development of HCV-specific antiviral therapies. This review will summarize our current knowledge about structure and function of these proteins and describe approaches pursued to identify effective antiviral compounds.
Institute for Virology, University of Mainz, Germany. bartnsch@mzdmza.zdv.uni-mainz.de
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Bartenschlager
D003546:Cysteine Endopeptidases / Q000378:metabolism; D004265:DNA Helicases / Q000037:antagonists & inhibitors; D010450:Endopeptidases / Q000378:metabolism; D016174:Hepacivirus / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008958:Models, Molecular; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors; D017361:Viral Nonstructural Proteins / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D003546:Cysteine Endopeptidases; D004265:DNA Helicases; D010450:Endopeptidases; D012324:RNA-Dependent RNA Polymerase; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C093542:NS4 protein, hepatitis C virus; C087036:NS-5 protein, hepatitis C virus; C107824:NS2-3 protease