TABLE 1.
Characterization of HCV NS3 protease variants in replicon cellsa
| Variant | EC50 (μM) of telaprevir for replicons | Fold change |
|---|---|---|
| Wild type | 0.49 ± 0.11 | 1.0 ± 0.2 |
| V36M | 3.4 ± 0.8 | 7.0 ± 1.6 |
| V36A | 3.6 ± 1.1 | 7.4 ± 2.2 |
| V36L | 1.1 ± 0.2 | 2.2 ± 0.4 |
| V36G | 5.4 ± 0.2 | 11.2 ± 0.4 |
| T54A | 3.0 ± 0.8 | 6.3 ± 1.7 |
| V36M + R155K | ∼30 | ∼62 |
| V36A + R155K | ∼20 | ∼40 |
| V36M + R155T | >30 | >62 |
| V36A + R155T | >30 | >62 |
| V36A + T54A | 9.7 ± 1.4 | 20.1 ± 2.9 |
| V36M + A156T | >30 | >62 |
a
The stable wild-type (strain Con1-mADE) and variant HCV subgenomic replicon cell lines were generated by using the T7 RNA runoff transcripts from the corresponding high-efficiency Con1 replicon plasmids. The average replicon EC50 values of telaprevir ± SDs were determined for the HCV replicon cell lines in the 48-h assay in three independent experiments. The fold change was determined by dividing the replicon EC50 of a given variant by that of the wild-type HCV replicon.