Laval Chan

TL;DR: X-ray crystal structures of two non-nucleoside analogue inhibitors bound to hepatitis C virus NS5B RNA-dependent RNA polymerase have been determined and suggest that the binding of these inhibitors interferes with a conformational change essential for the activity of the polymerase.

TL;DR: The structures of the NS5B polymerase/non-nucleoside inhibitor complexes bind at a common binding site, which is nearly 35 Å away from the polymerase active site and is located in the thumb domain, and the enzyme inhibitor complexes are stabilized by hydrogen bonding and van der Waals interactions.

TL;DR: Structural insights about the bioactive conformation of this class of molecules were deduced from a combination of modeling and transferred NOE (trNOE) studies.

TL;DR: The details of NS5B polymerase/inhibitor binding interactions coupled with the observed induced conformational changes provide new insights into the design of novel NNIs of HCV.

TL;DR: Results suggest that integrin antagonism of both αvβ3 and α5β1 are important for M MP-independent induction of apoptosis on COL and MMP-dependent inhibition of endothelial cell-denatured collagen interactions required for proliferation.