Figure 2.

Co-crystal structures of fragment hits

a and b. Compounds 1 and 2 were identified by fragment screening using crystals of the full length NS3/4a protein. The crystal structures show the compounds bound in the allosteric pocket, with binding predominantly dominated by van der Waals interactions. The pink mesh represents the electron density map (Fo-Fc omit map contoured at 3.9 σ) for each of the ligands. Compound 2 was one of the most potent fragments identified during the screening phase, with an IC₅₀ ~ 500 μM (LE ~ 0.30) against FL NS3/4a, and no inhibition of the protease domain alone.