An Inducible Cell-Cell Fusion System with Integrated Ability to Measure the Efficiency and Specificity of HIV-1 Entry Inhibitors
Figure 8
Dose-response curves for inhibition efficiency and specificity of known HIV-1 entry inhibitors.
A. The gp41-directed T20 peptide, gp120-directed BMS-806, and CCR5-directed Maraviroc were tested for inhibition and off-target effects with the dual reporter system using two different target cells, CEM-R5Luc1#21 (left) and Cf2Luc4#18 (right). Inhibition data were fitted to the logistic equation and the IC50 value for each tested compound and each target cell type was calculated. R2>0.96 for all curves. Red lines display relative R-luc activity and indicate the specificity of a compound; green lines are fitted curves for relative F-luc activity and indicate the inhibition of cell-cell fusion for each compound. The results shown are representative of those obtained in three or four independent experiments, each performed with more than three replicates. B. Reported IC50 values for the three inhibitors in antiviral assays [24], [27], [37], [62], [71], [72] (inhibition of the HIV-1MN isolate by BMS-806 was reported to be 743 nM [24] and this atypical value is excluded from the table).