Table 2.
Antiviral activity of inhibitor 2 against clinical HIV-1 isolates in PBMC cells
| IC50valuesa(nM) |
|||||
|---|---|---|---|---|---|
| Virusb | 2 | DRVc | SQVd | APVe | IDVf |
| HIV-1ERS104pre (wild-type: X4) | 29 | 3.5 | 12 | 33 | 26 |
| HIV-1MDR/MM (R5) | 150 (5) | 17 (5) | 190 (16) | 300 (9) | >1000 (>38) |
| HIV-1MDR/JSL (R5) | 550 (19) | 26 (7) | 330 (28) | 430 (13) | >1000 (>38) |
| HIV-1MDR/C (X4) | 300 (10) | 7 (2) | 36 (3) | 230 (7) | >1000 (>38) |
| HIV-1MDR/G (X4) | 340 (12) | 7 (2) | 29 (2) | 340 (10) | 290 (11) |
| HIV-1MDR/A (X4) | 21 (1) | 3 (1) | 81 (7) | 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, 162V, L63P, A71V, G73S, V82A, L90M, and I93L in HIV-1MDR/B; L10I, V11I, T12E, I15V, Ll9I, 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 the target cells and the inhibition of p24Gag protein production as the endpoint. All values were determined in triplicate.
X4 denotes CXCR4-tropic HIV-1 while R5 CCR5-tropic HIV-1.
DRV (darunavir).
SQV (saquinavir).
APV (amprenavir).
IDV (indinavir).