TABLE 4.
Antiviral activity of compounds with or without the OH moiety at C-5 of Tp-THF or C-4 of bis-THF against DRV-resistant HIV-1 variantsa
| Virus | Mean EC50 (nM) |
|||||
|---|---|---|---|---|---|---|
| Tp-THF |
bis-THF |
|||||
| GRL-0476 | GRL-015 | DRV | TMC126 | GRL-034 | GRL-087 | |
| HIV-1NL4-3 | 4.3 ± 1.3 | 3.3 ± 0.4 | 2.8 ± 0.4 | 0.27 ± 0.06 | 260 ± 70 | 27 ± 4 |
| HIV-1DRVRP20 | 270 ± 120 (64) | 3.3 ± 0.3 (1.0) | 36 ± 1 (13) | 19 ± 5 (70) | 269 ± 7 (1.1) | 30 ± 2 (1.1) |
| HIV-1DRVRP30 | 420 ± 60 (98) | 16 ± 3 (4.7) | 222 ± 31 (80) | 176 ± 62 (645) | 197 ± 37 (0.8) | 20 ± 3 (0.7) |
a
The amino acid substitutions identified in protease of HIV-1DRVRP20 compared to the wild-type HIV-1NL4-3 include L10I/I15V/K20R/L24I/V32I/M36I/M46L/L63P/A71T/V82A/L89M. Numbers in parentheses are fold changes in EC50s for each isolate compared to the EC50s for wild-type HIV-1NL4-3. All assays to determine the EC50s were conducted in duplicate or triplicate, and the data are means ± 1 standard deviation derived from the results of three independent assays.