TABLE 1.
Genotypes and phenotypes of BILN 2061-resistant coloniesa
| Replicon colony | BILN 2061
|
IFN-α IC50 (IU) | NS3 mutation(s)c | |
|---|---|---|---|---|
| SEAP IC50 (μM) | FCb | |||
| Wild type | 0.006 ± 0.002 | 1.6 ± 0.54 | ||
| SB1 | 7.37 ± 0.069 | 1,228 | 1.8 ± 0.85 | T72I, P88L, A156T |
| SB4 | 0.43 ± 0.041 | 72 | 1.5 ± 0.87 | R155Q |
| SB5 | 3.81 ± 0.231 | 635 | 1.9 ± 0.35 | I71T, A156T, T312A |
| SB6 | 3.32 ± 0.228 | 553 | 1.7 ± 0.58 | D168V, T260A |
a
Data shown are averages ± standard deviations of results from triplicate experiments.
b
FC, change in IC50 (n-fold) over that seen with the wild type.
c
Bold letters indicate amino acids in the protease domain. The others are in the helicase domain. The position of each mutation in the three-dimensional structure of the enzyme is shown in Fig. 2A.