FIG. 4.

Model of the mechanism of action of small-molecule inhibitors of CCR5 coreceptor function. gp120 is initially in a closed state, wherein the V1/V2 and V3 loops conceal the coreceptor binding site. Upon CD4 binding to gp120, conformational changes create and/or expose the coreceptor binding site. In the absence of inhibitor, the CCR5 Nt interacts with residues in the bridging sheet (BS) and the V3 stem, whereas ECL2 interacts with the V3 crown. In the presence of inhibitor, the conformation of ECL2 is modified such that it can no longer interact with the V3 crown, thus inhibiting viral entry.