TABLE 3.
Characterization of mutations in the thumb domain
| Polymerase(s) | Replication capacitya | Transient replicon IC50 (μM)
|
HCV NS5B570-BK IC50 (μM)c
|
NNI-1 KD (μM)d | |
|---|---|---|---|---|---|
| NNI-1b | NNI-2b | NNI-1 | |||
| WT | 1 | 0.3 ± 0.03 | 0.4 ± 0.06 | 0.14 ± 0.04 | 0.02 |
| L419M | 0.8 ± 0.13 | 15 ± 2.4 | 0.4 ± 0.05 | 11.0 ± 4.4 | 0.23 |
| M423T | 1.0 ± 0.21 | 8.4 ± 0.9 | 0.3 ± 0.04 | 15.0 ± 2.1 | 0.44 |
| M423I | 0.25 ± 0.02 | 4.4 ± 0.8 | 0.3 ± 0.07 | NDe | ND |
| I482L | 0.45 ± 0.16 | 16.6 ± 3.5 | ND | ND | ND |
| L419M/M423T | 0.19 ± 0.05 | 25 ± 2.4 | ND | ND | ND |
a
Replication capacity compared to the WT in the absence of inhibitor.
b
IC50 values represent the averages ± standard errors of means of the results from at least three independent experiments.
c
IC50 values represent the averages ± standard errors of means of the results from at least three independent experiments using the cIRES template.
d
KD values were determined using Biacore technology as detailed in Materials and Methods.
e
ND, not determined.