Submitted by Brian Barrish on June 29, - There was rain, and mist, but there was no physical lightning. But there was a change of the guard across all three contested divisions at the Eastern Regional Championships in suburban Philadelphia. On this day, similarly misty and moisty, it was the Hawks who were on the front foot from the beginning. On offense, Ryan Henry was busier than a bee in a beehive, helping to rack up possessions and get the forward liners involved early and often.
The exact nature of how these compounds have an inhibitory effect on HCV is unknown; however, major resistance mutations appear in the N-terminal region of NS5A that include the amphipathic helix and domain 1. The dimeric symmetry of these compounds suggests that they act on a dimer of NS5A, which is also consistent with the presence of dimers in crystals of NS5A domain 1 from genotype 1b. Genotype 1a HCV is less potently affected by these compounds and resistance mutations have a greater effect than in the 1b genotypes. We have obtained crystals of domain 1 of the important 1a NS5A homologue and intriguingly, our X-ray crystal structure reveals two new dimeric forms of this domain. These dimers also allow for new conformations of a NS5A expansive network which could explain its operation on the membranous web. Additionally, sulfates bound in the crystal structure may provide evidence for the previously proposed RNA binding groove, or explain regulation of NS5A domain 2 and 3 function and phosphorylation, by domain 1. Hence, current efforts being pursued in the treatment of HCV are focused on the development of direct acting antivirals DAAs.