title: Treatment of HCV infection with the novel NS3/4A protease inhibitors.
abstract: HCV NS3/4A serine protease inhibitors are the first class of direct acting antivirals (DAA) introduced in clinical practice. The first generation agents, selective against HCV genotype 1, are used in association with pegylated interferons and ribavirin allowing increased cure rates at the price of increased toxicity, significant drug interactions and high risk of selecting mutants conferring cross-resistance to the entire class. A large number of second-wave HCV protease inhibitors are currently in clinical development. Advancements include higher potency, activity against a wider number of genotypes, improved tolerability, easier dosing schedules, although their genetic barrier to resistance remains low, especially for subtype 1a, except for the most recent grazoprevir and ACH-2684. The most relevant progress regards the combination with other classes of DAA allowing construction of interferon-free regimens of short duration, good tolerability with exceptionally high cure rates.
authors.affiliation: UOC Malattie Infettive Universitarie, Dipartimento di Medicina e Specialistica, Azienda Ospedaliera Universitaria Senese, Siena, Italy; Istituto di Clinica delle Malattie Infettive, Università Cattolica del S Cuore, Roma, Italy. Electronic address: deluca.andrea@fastwebnet.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: De Luca
authors.affiliation: UOC Malattie Infettive Universitarie, Dipartimento di Medicina e Specialistica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Bianco
authors.affiliation: UOC Malattie Infettive Universitarie, Dipartimento di Medicina e Specialistica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Rossetti
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D011480:Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D011480:Protease 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; C080107:NS4B protein, flavivirus