BioCentury
ARTICLE | Targets & Mechanisms

Closing time for HCV protease

October 11, 2012 7:00 AM UTC

Astex Pharmaceuticals Inc. has used its fragment-based drug discovery platform to identify a new allosteric binding site on the full-length HCV NS3/4A protein and thinks compounds that bind the site can inhibit the protein's helicase activity in addition to its proteolytic activity.1 The result could be molecules with better efficacy than existing HCV drugs that target the protease active site.

The full-length HCV NS3/4A protein consists of a protease domain linked to a helicase domain. According to Astex president, director and cofounder Harren Jhoti, R&D efforts to target the NS3/4A complex have previously focused on compounds that target the active site of the protein's protease domain due to screening limitations-it is more technically challenging to express and crystallize the full-length protein than individual domains for screening purposes...