Figure 4.

Anti-HIV-1activity of 2 rationally designed RANTES mimetics. A) Anti-HIV-1 activity of RANTES mimetics R1.5G3 (acetyl-CFPYITRPGPIKEY-1Nal-Y-amide) and R2.0 (acetyl-CFPYITRPGTYHDY-1Nal-Y-Orn-amide) as evaluated using an envelope-mediated fusion assay. Assays were performed using PM1 cells chronically infected with the R5 HIV-1 strain BaL as effectors. Data represent averages ± sd from ≥3 independent experiments. Absolute cell fusion values for the untreated controls in these experiments ranged from 50.3 to 184.0 ODU/min. B) Comparative anti-HIV-1 activity of R1.5G3, R2.0, and 2 mutants of R2.0. As indicated, each mutated peptide separately contained one of the two mutations present in R2.0. X indicates the nonstandard amino acid 1Nal; O indicates ornithine. Data represent means ± sd from ≥3 independent experiments. C) Antiviral activity of R1.5G3 and R2.0 against a panel of primary CCR5-specific HIV-1 isolates minimally passaged ex vivo, as evaluated using an envelope-mediated fusion assay. PM1 cells were infected with each of 9 different CCR5-specific primary HIV-1 isolates and used as effector cells in the fusion assay. PM1 infected with HIV-1 BaL and SupT1 cells infected with the CXCR4-tropic isolate IIIB were used in parallel as controls. nt, not tested. Data represent mean IC₅₀ values from 2 independent experiments.