CD4-Specific Designed Ankyrin Repeat Proteins Are Novel Potent HIV Entry Inhibitors with Unique Characteristics
Figure 2
The selected CD4-specific DARPins potently inhibit HIV entry.
(A) Effect of the six selected CD4-specific DARPins of the 1st series (D1.1–D6.1) on the entry of replication-competent viruses (7 R5 and 3 X4 users) on PBMC. 70% inhibitory concentrations (IC70) derived in representative individual experiments are reported. (B) Inhibition of HIV entry by 1st and 2nd series DARPins: CD4-specific DARPins of the 2nd series (red to yellow) are more potent inhibitors of HIV entry as DARPins of the 1st series (dark blue to light blue). Inhibition of JR-FL, SF-162 and NL4-3 infection in a pseudotyped virus entry assay on TZM-bl cells (upper panels) and the respective replication competent viruses in a PBMC based assay (lower panels) was probed in parallel. The unselected DARPin E3_5 (gray) was used as control in the TZM-bl based assay. Data points are means of virus replication measured in two replicate wells. See Supporting Table S1 for a summary of the derived IC50 and IC70 values in these assays.