Dasabuvir

DB09183ApprovedSmall moleculeHepatitis C Virus Non-Nucleoside NS5B Palm Polymerase Inhibitor

Dasabuvir is a direct-acting antiviral agent used to treat specific hepatitis C virus (HCV) infections in combination with other antiviral agents. HCV is a single-stranded RNA virus that is categorized into nine distinct genotypes, with genotype 1 being the most common in the United States, and affecting 72% of all chronic HCV patients.

Mechanism: Dasabuvir is a non-nucleoside inhibitor of the HCV RNA-dependent RNA polymerase encoded by the NS5B gene, which is essential for replication of the viral genome. Based on drug resistance mapping studies of HCV genotypes 1a and 1b, dasabuvir targets the palm domain of the NS5B polymerase, and is therefore referred to as a non-nucleoside NS5B-palm polymerase inhibitor. The EC50 values of dasabuvir against genotype 1a-H77 and 1b-Con1 strains in HCV replicon cell culture assays were 7.7 nM and 1.8 nM, respectively.
By binding to NS5b outside of the active site of the enzyme, dasabuvir induces a conformational change thereby preventing further elongation of the nascent viral genome. A limitation of binding outside of the active site is that these binding sites are poorly preserved across the viral genotypes. This results in a limited potential for cross-genotypic activity and increased potential for development of resistance. Dasabuvir is therefore limited to treating genotypes 1a and 1b, and must be used in combination with other antiviral products.
Curator reviewed
Primary indication: Dasabuvir, in combination with DB09296, DB09297, and DB00503 (as Viekira Pak) is indicated for the treatment of patients with HCV genotype 1a with DB00811 or genotype 1b without DB00811 including those with compensated cirrhosis.Curator reviewed · 2 structured indications
Formula / weight: C₂₆H₂₇N₃O₅S · 493.58 g/mol (avg)
First approval: Canada, 2014 · United States, 2014
Code names: ABT-333
Brand names: Viekira Pak