TABLE 5.
Sensitivities of mutant pseudoviruses to NBD compoundsa
| Virus | IC50 (μM) ± SDa |
|||
|---|---|---|---|---|
| NBD-556 | NBD-09027 | NBD-11008 | BMS-378806 (nM) | |
| HXB2 WT | 7.4 ± 0.8 | 4.4 ± 0.4 | 3 ± 1 | ∼1 |
| NBD-11008 mutants | ||||
| V208I | ∼30 | ∼43 | ∼42 | ∼1 |
| NN301–302KI | >48 | >43 | ∼64 | ∼1 |
| S375Y | ∼60 | ∼65 | >64 | >400 |
| S405L | 7.9 ± 0.5 | 8 ± 0.5 | 4.5 ± 0.4 | ∼1 |
| NN301–302KI/S375Y | ≥60 | ∼65 | >64 | >400 |
| NN301–302KI/S405L | >60 | >65 | >64 | ∼1 |
| S375Y/S405L | >45 | >43 | ∼64 | >400 |
| NN301–302KI/S375Y/S405L | >60 | >65 | >64 | >400 |
| V208I/NN301–302KI/S375Y/S405L | ∼45 | ∼43 | >42 | >400 |
| NBD-09027 mutants | ||||
| NN301–302KI | >48 | >43 | ∼64 | ∼1 |
| K432R | 14.8 ± 3.3 | 21.7 ± 1.2 | 16.4 ± 1.5 | ∼1 |
| V782L | 9.2 ± 1 | 19.1 ± 2.7 | 7.8 ± 3 | ∼1 |
| NN301–302KI/K432R | 38 ± 0.6 | ∼30 | ∼42 | ∼1 |
| NN301–302KI/V782L | 13.8 ± 1.1 | 19.1 ± 3 | 15.5 ± 1.3 | ∼1 |
| K432R/V782L | ∼21 | ∼40 | ∼38 | ∼1 |
| NN301–302KI/K432R/V782L | >37 | >65 | ∼32 | ∼1 |
| BMS-378806 mutants | ||||
| M475I | ∼45 | ∼33 | ∼32 | >400 |
| M426L | 14.4 ± 0.3 | 11.9 ± 1.6 | >38 | >400 |
| M434I | 1.2 ± 0.8 | 1 ± 0.2 | 0.68 ± 0.1 | >400 |
| M434I-I595F | 4.7 ± 1 | 2.7 ± 0.3 | 4.3 ± 0.9 | >400 |
| S375H | 19 ± 1.5 | 9 ± 0.7 | >43 | >400 |
a
Values representing the means ± standard deviations were obtained from three independent experiments. The NBD CC50s were >118, >87, >85 for NBD-556, NBD-09027, and NBD-11008, respectively.