Table 8.
Effect of selected mutations on the antiviral phenotype of replicons
| Mutation | Fold increase in EC50 compared to WTa |
|||||
|---|---|---|---|---|---|---|
| Protease inhibitors |
Nonnucleoside RdRp inhibitors |
Nucleoside RdRp inhibitor 2′-CMC | ||||
| BILN 2061 | VX-950 | A-782759 | TCA | JT-16 | ||
| D168V (NS3) | >265 | 0.20 ± 0.16 | 0.90 ± 0.44 | 0.24 ± 0.19 | 0.85 ± 0.31 | 1.2 ± 0.31 |
| S282T | ND | 1.98 ± 1.0 | 1.4 ± 0.89 | 1.3 ± 0.40 | 0.96 ± 1.1 | 4 ± 0.78 |
| C316Y | 0.32 ± 0.30 | 0.21 ± 0.080 | 607 ± 177 | 0.31 ± 0.35 | 0.52 ± 0.056 | 0.83 ± 0.39 |
| 316-445 | 0.74 ± 0.45 | 1.3 ± 1.3 | >719 | 0.27 ± 0.15 | 0.72 ± 0.42 | 0.88 ± 039 |
| M414T | 1.4 ± 0.70 | 0.83 ± 0.14 | 285 ± 112 | 2 ± 1.5 | 0.84 ± 0.72 | 0.62 ± 0.33 |
| M423T | ND | 1.3 ± 0.31 | 0.56 ± 0.21 | 56 ± 11 | 0.88 ± 0.15 | ND |
| C445F | 0.93 ± 0.19 | 0.77 ± 0.66 | 3 ± 0.67 | 0.17 ± 0.14 | 1.1 ± 0.21 | 0.93 ± 0.39 |
| Y452H | 0.90 ± 0.60 | 0.37 ± 0.37 | 7 ± 1.4 | 1.6 ± 1.3 | 1.9 ± 1.8 | 1.6 ± 0.28 |
| 445-452 | 1.2 ± 0.97 | 0.65 ± 0.69 | 4 ± 1.5 | 0.35 ± 0.14 | 1.2 ± 0.47 | 0.57 ± 0.14 |
| P495L | ND | 2 ± 1.1 | 8 ± 0.63 | ND | >30 | 0.71 ± 0.33 |
a
Resistance was set as ≥3-fold EC50 increase compared to WT EC50. Data are mean values for ≥2 independent experiments. Boldface indicates resistance. ND, not determined.