FIG. 5.
N36Mut(e,g) displays synergistic antiviral activity with both neutralizing and nonneutralizing Fabs directed against the N-HR of gp41. Dose-response curves for antiviral activity of N36Mut(e,g) alone (green), Fab alone (red), and Fab + N36Mut(e,g) in two fixed combination ratios (blue) against HXB2 (A and C) and SF162 (B and D) Env-pseudotyped viruses are shown. The Fabs are bF-3674 in panels A and B, bF-3670 in panel C, and mF-3674 in panel D. The concentrations for the combination curves in panels A, B, and D refer to the concentration of Fab, while in panel C they refer to the concentration of N36Mut(e,g). The experimental data (averages from six to eight experiments, with error bars representing standard deviations) are fit by nonlinear least-squares minimization to a simple binding isotherm given by % infection = 100/(1 + [I[]/IC50), where [I] is the concentration of fusion inhibitor. IC50s, DRIs, and CIs are provided in Tables 1 and 2.