TABLE 5.
Activity of paritaprevir or ombitasvir against chimeric GT4 transient subgenomic replicons containing amino acid variants in NS3 or NS5A
| HCV GT4 replicon subtype by targeta | Varianta | EC50 (mean ± SD) (nM)b | Fold resistancec |
|---|---|---|---|
| NS3 | |||
| 4a | Wild typed | 0.048 ± 0.0066 | |
| D168V | 15 ± 1.6 | 313 | |
| 4d | Wild type | 0.015 ± 0.001 | |
| Y56H | 0.12 ± 0.028 | 8.0 | |
| D168V | 4.7 ± 0.9 | 313 | |
| Y56H+D168V | 188 ± 50 | 12,533 | |
| NS5A | |||
| 4a | Wild type | 0.00035 ± 0.00007 | |
| L28V | 0.008 ± 0.0028 | 23 | |
| 4d | Wild type | 0.00038 ± 0.00006 | |
| L28S | NDe | ||
| L28V | 0.118 ± 0.016 | 310 | |
| M31I | 0.00096 ± 0.00012 | 2.5 | |
| M31L | 0.00039 ± 0.00008 | 1.0 | |
| T58A | 0.00053 ± 0.00002 | 1.4 | |
| T58P | 0.00042 ± 0.00004 | 1.1 | |
| T58S | 0.00052 ± 0.00009 | 1.4 | |
| L28S+M31I | ND | ||
| L28V+T58S | 0.289 ± 0.029 | 760 |
a
Chimeric replicons containing the NS3 or NS5A gene cloned from a GT4a or GT4d treatment-naive clinical isolate.
b
The mean ± SD EC50 values were derived from the results from at least three independent experiments.
c
Calculated as variant EC50/wild-type EC50.
d
Wild type indicates that amino acids at resistance-associated positions match those of reference sequence 4a-ED43 or 4d-QC382.
e
ND, EC50 could not be determined due to the poor replication capacity of the chimeric replicon.