Table 2.
Antiviral activity (IC50) of inhibitors 3d and 3h against clinical HIV-1 isolates in PBMC cells (nM).
| Virus | IC50 (nM) valuesa |
|||||
|---|---|---|---|---|---|---|
| 3d | 3h | DRV | RTV | APV | IDV | |
| ERS104pre (wild-type) | 20 | 6 | 3.5 | 34 | 33 | 26 |
| MDR/TM | 220 (11) | 64 (10) | 4 (1) | >1000 (>29) | 290 (9) | >1000 (>38) |
| MDR/MM | 250 (13) | 110 (5) | 17 (5) | >1000 (>29) | 300 (9) | >1000 (>38) |
| MDR/JSL | 500 (25) | 330 (55) | 26 (7) | >1000 (>29) | 430 (13) | >1000 (>38) |
| MDR/B | 340 (17) | 230 (38) | 26 (7) | >1000 (>29) | 320 (10) | >1000 (>38) |
| MDR/C | 210 (11) | 160 (27) | 7 (2) | >1000 (>29) | 230 (7) | >1000 (>38) |
| MDR/G | 360 (18) | 300 (50) | 7 (2) | >1000 (>29) | 340 (10) | 290 (11) |
| MDR/A | 20 (1) | 13 (2) | 3 (1) | >1000 (>29) | 100 (3) | >1000 (>38) |
Amino acid substitutions identified in the protease-encoding region compared to the consensus type B sequence cited from the Los Alamos database include L63P in HIV-1ERS104pre; L10I, K14R, L33I, M36I, M46I, F53I, K55R, I62V, L63P, A71V, G73S, V82A, L90M, and I93L in HIV-1MDR-B; L10I, V11I, T12E, I15V, L19I, R41K, M46L, L63P, A71T, V82A, and L90M in HIV-1MDR-G; L10I, K14R, R41K, M46L, I54V, L63P, A71V, V82A, L90M, I93L in HIV-1MDR-TM; L10I, L24I, I33F, E35D, M36I, N37S, M46L, I54V, R57K, I62V, L63P, A71V, G73S, and V82A in HIV-1MDR-JSL; and L10I, K43T, M46L, I54V, L63P, A71V, V82A, L90M, and Q92K in HIV-1MDR-MM. HIV-1ERS104pre served as a source of wild-type HIV-1. The IC50 values were determined by employing PHA-PBMC (phytohemaglutinin-activated peripheral blood mononuclear cells) as target cells and the inhibition of p24Gag protein production as the endpoint. All values were determined in triplicate. DRV (Darunavir), SQV (Saquinavir), APV (Amprenavir), IDV (Indinavir).