TABLE 5.
Susceptibility of resistant mutant replicons to AG-021541 and other HCV inhibitors in the transient assay
| Replicon construct | Fold change in EC50 relative to wt replicon with the indicated inhibitora:
|
||||||
|---|---|---|---|---|---|---|---|
| IFN | AG-021541 | Compound B | NM107 | HCV-796 | A-782759 | Compound C | |
| M423T | 1.0 | >31 | 5625 | 0.8 | 1.2 | 0.7 | 1.3 |
| M423V | 1.0 | >44 | 781 | 1.4 | 0.9 | 0.7 | 0.2 |
| M423I | 1.0 | >44 | 179 | 1.4 | 0.9 | 1.4 | 1.4 |
| M426T | 0.9 | 4.5 | 4.0 | 0.8 | 0.9 | 1.2 | 1.6 |
| I482T | 1.1 | 7.0 | 5.6 | 1.4 | 0.5 | 0.3 | 1.1 |
| V494A | 0.4 | 6.9 | 11 | 0.7 | 0.2 | 0.6 | 0.2 |
| S282T | 1.2 | 1.2 | 0.9 | 18 | 1.1 | 1.7 | 0.6 |
| C316N | 0.5 | 0.9 | 0.8 | 0.5 | 9.0 | 1.5 | 0.5 |
| M414T | 0.7 | 0.6 | 0.7 | 0.8 | 0.6 | 169 | 0.3 |
| P495L | 1.4 | 2.5 | 3.5 | 1.0 | 0.7 | 8.7 | 16 |
| P495S | 1.1 | 0.5 | 0.6 | 1.0 | 0.5 | 2.9 | 13 |
a
The susceptibility of AG-021541-resistant replicons to IFN and various HCV polymerase inhibitors was evaluated in the reporter replicon assay. Cells were exposed to compounds for 3 days before RLuc activity was determined. Results showing at least fourfold increases in the EC50 are indicated in boldface.