TABLE 5.
Antiviral activity of pibrentasvir against HCV replicons of genotypes 1a and 1b containing NS5A with amino acid substitutions that confer resistance to other NS5A inhibitors
| HCV genotype and NS5A amino acid substitution(s) | Pibrentasvir EC50a |
Replication efficiency (%)b | |
|---|---|---|---|
| Mean ± SD (pM) | Fold changeb | ||
| 1a-H77 | |||
| Wild type | 0.72 ± 0.45 | 100 | |
| M28T | 1.5 ± 1.1 | 2.1 | 89 |
| M28V | 1.3 ± 0.86 | 1.8 | 87 |
| Q30E | 1.7 ± 0.39 | 2.4 | 70 |
| Q30H | 0.74 ± 0.21 | 1.0 | 90 |
| Q30R | 1.2 ± 0.62 | 1.7 | 86 |
| L31M | 0.76 ± 0.11 | 1.1 | 141 |
| L31V | 0.96 ± 0.85 | 1.3 | 297 |
| P32L | 1.2 ± 0.43 | 1.7 | 19 |
| H58D | 0.80 ± 0.17 | 1.1 | 97 |
| Y93C | 1.2 ± 0.57 | 1.7 | 22 |
| Y93H | 4.8 ± 1.5 | 6.7 | 40 |
| Y93N | 5.1 ± 2.1 | 7.1 | 35 |
| M28T+Q30R | 1.2 ± 0.21 | 1.6 | 28 |
| M28T+Y93C | 2.2 ± 0.47 | 3.1 | 18 |
| Q30L+Y93H | 0.42 ± 0.09 | 0.6 | 27 |
| Q30R+L31M | 1.7 ± 0.34 | 2.4 | 46 |
| Q30R+H58D | 77 ± 2.1 | 108 | 46 |
| Q30R+Y93C | 2.8 ± 0.64 | 3.8 | 5.3 |
| Q30R+Y93H | 187 ± 110 | 260 | 11 |
| L31M+Y93C | 4.4 ± 0.55 | 6.1 | 28 |
| L31V+Y93H | 68 ± 36 | 94 | 73 |
| M28T+Q30R+L31M | 3.3 ± 0.41 | 4.6 | 44 |
| Q30R+L31M+Y93C | 30 ± 1.0 | 42 | 6.8 |
| 1b-Con-1 | |||
| Wild type | 1.9 ± 0.80 | 100 | |
| L28T | 1.7 ± 0.44 | 0.9 | 18 |
| Y93H | 1.1 ± 0.27 | 0.6 | 38 |
| Y93N | 1.2 ± 0.25 | 0.6 | 52 |
| L31M+Y93H | 1.3 ± 0.24 | 0.7 | 15 |
| L31V+Y93H | 1.7 ± 0.31 | 0.9 | 30 |
| P58S+Y93H | 1.5 ± 0.45 | 0.8 | 44 |
a
As determined in transient-transfection assays.
b
Fold change or replication efficiency is relative to the value of the respective wild-type replicon.