TABLE 6.
Antiviral activity of pibrentasvir against HCV replicons containing NS5A from genotypes 2 to 6 with amino acid substitutions that confer resistance to other NS5A inhibitors
| HCV genotype and NS5A amino acid substitution(s) | Pibrentasvir EC50a |
|
|---|---|---|
| Mean ± SD (pM) | Fold change | |
| 2a | ||
| Wild typeb | 0.99 ± 0.36 | |
| T24A | 1.3 ± 0.30 | 1.3 |
| F28S | 1.2 ± 0.17 | 1.2 |
| 2b | ||
| Wild typec | 1.2 ± 0.39 | |
| L28F | 0.94 ± 0.27 | 0.8 |
| L31M | 1.5 ± 0.33 | 1.2 |
| L31V | 0.64 ± 0.20 | 0.5 |
| 3a | ||
| Wild type | 0.65 ± 0.16 | |
| M28T | 1.1 ± 0.02 | 1.7 |
| Y93H | 1.5 ± 0.19 | 2.3 |
| 4a | ||
| Wild type | 0.78 ± 0.14 | |
| L28V | 0.85 ± 0.23 | 1.1 |
| L30H | 1.1 ± 0.51 | 1.3 |
| 5a | ||
| Wild type | 0.93 ± 0.20 | |
| L28I | 0.98 ± 0.14 | 1.1 |
| L31F | 1.9 ± 0.11 | 2.1 |
| L31V | 0.75 ± 0.24 | 0.8 |
| 6a | ||
| Wild typed | 1.0 ± 0.31 | |
| L31V | 1.0 ± 0.38 | 1.0 |
| T58A | 1.4 ± 0.45 | 1.4 |
| T58N | 1.8 ± 0.71 | 1.8 |
a
As determined in transient-transfection assays. Fold change is relative to the value of the respective wild-type replicon.
b
The 2a wild-type replicon has M31 in NS5A.
c
The 2b wild-type replicon has L31 in NS5A.
d
The 6a wild-type replicon has L28 in NS5A.