Induced‐Fit Binding of the Macrocyclic Noncovalent Inhibitor TMC435 to its HCV NS3/NS4A Protease Target

Abstract

If the shoe fits: TMC435, a noncovalent small-molecule inhibitor of the hepatitis C virus (HCV) NS3/NS4A protease, is currently undergoing clinical evaluation as an HCV therapeutic. In the crystal structure of the noncovalent NS3/NS4A protease–TMC435 complex the bound inhibitor exploits induced-fit binding. The new structure is consistent with the emerging view of viral resistance to NS3/NS4A protease inhibitors. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.