TABLE 7.
Antiviral activity of pibrentasvir against HCV replicons containing amino acid substitutions that confer resistance to NS3/4A protease or NS5B polymerase inhibitors
| DAA target and HCV genotype | Amino acid substitution | Pibrentasvir EC50 (pM)a | Fold change in pibrentasvir EC50a |
|---|---|---|---|
| NS3 | |||
| 1a | Wild type | 0.94 | |
| R155K | 0.72 | 0.76 | |
| D168A | 0.77 | 0.82 | |
| D168V | 0.79 | 0.84 | |
| 1b | Wild type | 2.7 | |
| R155K | 1.4 | 0.54 | |
| A156T | 1.4 | 0.52 | |
| D168V | 2.5 | 0.91 | |
| NS5B | |||
| 1a | Wild type | 1.3 | |
| C316Y | 1.3 | 1.0 | |
| M414T | 1.6 | 1.2 | |
| Y448C | 1.0 | 0.77 | |
| Y448H | 1.0 | 0.77 | |
| S556G | 1.6 | 1.2 | |
| S559G | 0.6 | 0.46 | |
| 1b | Wild type | 1.8 | |
| S282T | 3.1 | 1.7 | |
| C316Y | 1.8 | 1.0 | |
| Y448H | 1.9 | 1.1 | |
| S556G | 1.9 | 1.1 |
a
As determined in transient-transfection assays. Fold change is relative to the value of the respective wild-type replicon.