Daclatasvir: a team player rather than a prima donna in the treatment of hepatitis C

With the introduction of direct-acting antivirals (DAA), the treatment for chronic hepatitis C is evolving at an astonishingly rapid pace.1 Among DAAs, HCV NS5A inhibitors show substantial promise as anti-HCV therapeutics. NS5A inhibitors in clinical development include daclatasvir (DCV), ledipasvir, ombitasvir and MK-8742.2 With in vitro anti-HCV activities in the low picomolar range, these represent the most potent class of DAAs to target HCV. The HCV NS5A protein is known to function in multiple aspects of the HCV life cycle, including roles in viral replication and assembly, as well as complex interactions with cellular factors. Not being associated with any measurable enzymatic activity, NS5A was not considered ‘druggable’ for a very long time. In fact, the first small-molecule NS5A inhibitors were discovered by random screening using the HCV replicon system. The initial lead compounds had only moderate potency, but subsequent medicinal chemistry efforts resulted in...

Source: Gut - May 8, 2015 Category: Gastroenterology Authors: Aghemo, A., De Francesco, R. Tags: Commentary Source Type: research