A second target for the peptoid Tat/transactivation response element inhibitor CGP64222: Inhibition of human immunodeficiency virus replication by blocking CXC-chemokine receptor 4-mediated virus entry

The peptoid CGP64222 has been previously demonstrated to inhibit the human immunodeficiency virus (HIV) Tat/transactivation response element complex f ormation. It has previously been shown that CGP64222 selectively inhibits H IV-1 long terminal repeat-driven gene expression and HIV-1(LAV) replication in lymphocytes. Here, we show that CGP64222 inhibits the replication of a wide range of laboratory strains of HIV-1 and HIV-2 in MT-4 cells. However, CGP64222 proved inactive in MT-4 cells against HIV-1 strains that are resi stant to the bicyclams. The bicyclams are known to specifically interact wi th CXC-chemokine receptor 4, the main coreceptor used by T-tropic HIV strai ns to enter the cells. Mechanism of action studies revealed that CGP64222 c an inhibit the HIV replicative cycle, also through a selective interaction with the CXC-chemokine receptor 4 coreceptor.