Table 4.
Kinetic parameters of TMC647055 interactions with NS5B clinical isolates of different genotypesa
| NS5B genotype of purified protein | No. of isolates |
kon (1/Ms) |
koff (1/s) |
KD (M) |
t1/2 (min) |
||||
|---|---|---|---|---|---|---|---|---|---|
| Median | Range | Median | Range | Median | Range | Median | Range | ||
| Wild-type Con1b | 2.2E+04 | 8.9E−05 | 4.1E−09 | 130.5 | |||||
| 1a | 5 | 7.5E+04 | (3.9–10.9)E+04 | 4.7E−04 | (3.1–8.2)E−04 | 7.3E−09 | (2.9–10.5)E−09 | 24.5 | 14.1–37.2 |
| 1b | 5 | 3.1E+04 | (2.3–3.7)E+04 | 9.5E−05 | (4.9–14.1)E−05 | 3.9E−09 | (2.3–5.1)E−09 | 121.4 | 82.1–234.0 |
| 2b | 3 | 1.5E+04 | (4.4–42.9)E+03 | 1.5E−02 | (1.2–1.7)E−02 | 8.8E−07 | (2.8–38.5)E−07 | 0.8 | 0.7–1.0 |
| 3a | 3 | 6.0E+04 | (2.5–9.5)E+04 | 3.6E−04 | (3.6–4.5)E−04 | 6.1E−09 | (4.0–19.1)E−09 | 31.7 | 25.5–32.1 |
| 4a | 3 | 2.1E+05 | (1.8–2.9)E+05 | 4.4E−04 | (3.9–6.0)E−04 | 2.0E−09 | (1.4–3.8)E−09 | 26.2 | 19.1–29.6 |
| 5a | 1 | 4.0E+04 | 9.7E−04 | 2.1E−08 | 11.9 | ||||
| 6a | 1 | 5.1E+04 | 1.6E−03 | 3.0E−08 | 7.3 | ||||
a
The interaction was analyzed using the SPR reversible capture assay for HCV NS5B.