TABLE 4.
Phenotypic characterization of HCV-796-resistant variants of GT-1b or GT-1a
| Replicon background and NS5B phenotype or mutation(s) | Replication capacitya | EC50 (μM ± SD)b of:
|
|
|---|---|---|---|
| HCV-796 | NNI-1 (thumb II inhibitor) | ||
| GT-1b background | |||
| WT | 1 | 0.006 ± 0.002 | 0.16 ± 0.03 |
| C316Y | 0.6 ± 0.2 | 0.56 ± 0.1 | 0.20 ± 0.04 |
| GT-1a background | |||
| WT | 1 | 0.004 ± 0.001 | 0.63 ± 0.12 |
| L392F | 2.1 ± 0.5 | 0.008 ± 0.001 | 0.58 ± 0.11 |
| M414T | 2.2 ± 1.1 | 0.007 ± 0.0004 | 0.53 ± 0.17 |
| C316Y | 0.07 ± 0.03 | 1.7 ± 0.5 | 0.39 ± 0.10 |
| C316Y/L392F | 0.71 ± 0.12 | 3.2 ± 0.8 | 0.34 ± 0.13 |
| C316Y/M414T | 1.2 ± 0.4 | 2.8 ± 1.1 | 0.30 ± 0.07 |
| L392F/M414T | 0.9 ± 0.5 | 0.022 ± 0.009 | 0.39 ± 0.1 |
a
The replication capacities were determined as the ratio of the firefly luciferase signal at 4 days postelectroporation to the luciferase signal at 4 h postelectroporation. The replication capacities of the mutants were expressed as their normalized replication efficiencies compared to that of the WT, set at a value of 1. The values are presented as means ± standard deviations of results from at least three independent experiments.
b
EC50 values are presented as means ± standard deviations of results from at least four independent experiments.