Inhibition of HIV-1 transcription and replication by 1H4.

<p>A. The model of 1H4 interaction with PP1. 1H4 occupies hydrophobic sites of Phe68’ and Val 66′ side chains, interacts with Gln262 and forms a network of hydrogen bonds with Arg261 and Cys291. B. Chemical structure of 1H4. C. Inhibition of HIV-1 transcription in 293T cells. 293T cells were transfected with HIV-1 LTR-LacZ, CEM-GFP and Tat expressing vectors and treated with the indicated concentrations of 1H4 and 1G3 compounds. At 24 hours after the transfection, the cells were lysed and analyzed for green fluorescence and for β-galactosidase activity. D. Toxicity in CEM cells. CEM cells were treated with the indicated concentrations of 1H4, 1G3 and toxic A02 compound for 24 hours. The viability was determined using trypan exclusion assay and automated cell counter (Nexcelcom). E. HIV-1 replication is inhibited by 1H4. MT4 cells were infected with recombinant pNL4-3 HIV-1 and treated with different concentrations of 1H4 or inactive control 1G3. The RT activities were determined over the course of 8 days.