Table 4.
GS-5885 and daclatasvir EC50s and fold shifts to NS5A resistance-associated mutations
| NS5A strain or mutant | GS-5885 |
Daclatasvir |
||
|---|---|---|---|---|
| Mean EC50 ± SD (nM)a | EC50 fold changeb | Mean EC50 ± SD (nM)a | EC50 fold changeb | |
| 1a-H77 | 0.051 ± 0.044 | 1.0 | 0.023 ± 0.017 | 1.0 |
| M28V | 0.078 ± 0.011 | 0.6 ± 0.08 | 0.02 ± 0.001 | 1.1 ± 0.13 |
| M28T | 1.801 ± 0.77 | 61 ± 8.2 | 8.85 ± 2.0 | 390 ± 125 |
| Q30H | 5.301 ± 2.55 | 183 ± 51 | 7.03 ± 0.5 | 309 ± 32.8 |
| Q30R | 12.42 ± 10.44 | 632 ± 176 | 5.73 ± 0.2 | 252 ± 15.1 |
| Q30E | 44.05 ± 14.71 | 5,458 ± 1,166 | 85.53 ± 16.8 | 3,764 ± 1,045 |
| L31M | 14.61 ± 3.97 | 554 ± 65 | 5.81 ± 1.5 | 197 ± 25 |
| H58D | 32.73 ± 8.63 | 1,127 ± 101 | 2.68 ± 0.01 | 118 ± 0.6 |
| Y93C | 48.72 ± 10.22 | 1,602 ± 372 | 12.28 ± 2.4 | 540 ± 149 |
| Y93H | 86.43 ± 21.69 | 1,677 ± 603 | 73.94 ± 28.6 | 2,082 ± 121 |
| Y93N | >500 | >14,706 | >500 | >32,000 |
| Q30R+Y93C | 56.45 ± 5.55 | 1,046 ± 391 | 229.14 ± 222.7 | 4,213 ± 646 |
a
The EC50 values and standard deviations (SD; n ≥ 2) for site-directed mutants in a 1a-H77 replicon were determined for GS-5885 and daclatasvir.
b
Fold change in EC50 is calculated relative to the baseline EC50.