Background information and sequence alignment.

<p>(<b>A</b>) Schematic of the HCV polyprotein with cleavage sites of the two proteases, NS2 and NS3. (<b>B</b>) Structures of two FDA-approved NS3/4A inhibitors. (<b>C</b>) Structure of the NS3/4A serine protease, with the NS3 protease domain colored in cyan, and the co-factor NS4A (beta strand) shown in red. The active site residues, S139, H57 and D81, sit on the protein-protein interaction surface and are shown as stick figures in green. The amino acids prone to mutation in the binding site enabling drug resistance against both Telaprevir and Boceprevir are shown as stick figures in magenta (V36, F43, T54, R155 and A156). Images were prepared using Chimera v1.6.1, UCSF, 2012 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0075144#pone.0075144-Pettersen1" target="_blank">[37]</a>. (<b>D</b>) Sequence alignment of NS3 proteases from four HCV genotypes.