FIG 5.

Screen of a purinergic library reveals that compounds selective for P2X receptors inhibit viral membrane fusion. (A) Seventy-one purinergic compounds listed on the basis of their level of inhibition of HIV-1 membrane fusion, which was based on the averages of two independent determinations with the compounds at 100 μM. (B) The compounds were categorized on the basis of their toxicity and inhibitory activity. Five compounds had inhibitory activity without toxicity, while five compounds had inhibitory activity at a toxic level. The remaining 61 compounds had no effect. (C) Dot plot of HIV fusion-inhibitory activity of all compounds grouped on the basis of their reported receptor specificity. Compounds reported to have nonselective inhibition against either P2X or P2Y receptors are placed in the P2X/P2Y category, compounds reported to have only P2Y activity are placed in the P2Y category, and the remaining compounds have some reported activity on the adenosine receptors and are placed in the A1/A2 category. *, P < 0.0005. (D) Titrations of the four most potent inhibitors were conducted using the Cre-Lox assay to measure viral fusion during cell-free and cell-to-cell infection. IC₅₀s were calculated using nonlinear regression analysis of a log concentration (agonist) versus the normalized response with a variable slope. The structure of each compound is listed below the plot.