title: New therapeutic strategies in HCV: second-generation protease inhibitors.
abstract: Telaprevir and boceprevir are the first direct-acting antiviral agents approved for use in HCV treatment and represent a significant advance in HCV therapy. However, these first-generation drugs also have significant limitations related to thrice-daily dosing, clinically challenging side-effect profiles, low barriers to resistance and a lack of pan-genotype activity. A second wave of protease inhibitors are in phase II and III trials and promise to provide a drug regimen with a better dosing schedule and improved tolerance. These second-wave protease inhibitors will probably be approved in combination with PEG-IFN and Ribavirin (RBV), as well as future all-oral regimens. The true second-generation protease inhibitors are in earlier stages of development and efficacy data are anxiously awaited as they may provide pan-genotypic antiviral activity and a high genetic barrier to resistance.
authors.affiliation: University of Florida, FL, USA.
authors.forename: Virginia C
authors.initials: VC
authors.lastname: Clark
authors.forename: Joy A
authors.initials: JA
authors.lastname: Peter
authors.forename: David R
authors.initials: DR
authors.lastname: Nelson
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015195:Drug Design; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D016174:Hepacivirus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006526:Hepatitis C / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D047908:Intracellular Signaling Peptides and Proteins; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D015842:Serine Proteinase Inhibitors / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D016896:Treatment Outcome; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D002352:Carrier Proteins; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D047908:Intracellular Signaling Peptides and Proteins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; D015842:Serine Proteinase Inhibitors; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C455041:NS4A cofactor peptide, Hepatitis C virus; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a