Figure 3.
(A) Cornish–Bowden plot for compound 2 and Zika virus NS2B-NS3 protease (gZiPro). The intersection point (−Ki) of the four independent linear fits with the abscissa indicates a noncompetitive inhibition mechanism with a Ki value of 0.44 μM.22 The same value was obtained from nonlinear least-squares fits using a noncompetitive binding model (Graphpad Prism 7.0; Table S3). (B) Inhibition of Zika virus NS2B-NS3 protease (bZiPro) activity by the noncompetitive inhibitor 2 and the covalently binding active-site inhibitor cn-716. Addition of compound 2 in the presence of cn-716 results in synergistically decreased protease activity, suggesting that 2 binds at an allosteric site.