Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5806888 | Current Opinion in Virology | 2013 | 7 Pages |
â¢HCV NS5A replication complex inhibitors.â¢Exceptional potency with broad genotype coverage translated in clinical studies.â¢Important component for HCV combination therapy.â¢Potential mode of inhibition.
Treatment of Hepatitis C Virus (HCV) infection is rapidly evolving with the introduction of direct acting antiviral agents (DAA). HCV NS5A replication complex inhibitors, exemplified by Daclatasvir (BMS-790052), represent a new class of DAA. The exceptional in vitro potency (EC50 values at pM to low nM range) and broad genotype coverage of NS5A inhibitors have translated to robust anti-HCV effects in infected patients, making NS5A inhibitors an essential component of effective HCV DAA combination therapies. On the basis of drug-induced resistance substitutions and computer modeling, NS5A inhibitors most likely act at the N-terminus of NS5A (domain I). Mechanism of inhibition studies to elucidate the exquisite potency of these inhibitors have generated several working models.