Table 2.
Predicted and measured impact of BSVs on antiviral activity of ketoamides1.
| Genotype 1a HCV |
IRECS | EC50 [nM] | Fold-change in EC50 | |||
|---|---|---|---|---|---|---|
| Boceprevir | TLL | Boceprevir | Telaprevir | Boceprevir | Telaprevir | |
| H77S.3/GLuc2A | - | - | 870 (±48) | 120 (±10) | 1.0 | 1.0 |
| Q41H | MiN2 | MiN | 1040 (±60) | 410 (±10) | 1.2 | 3.5 |
| T42A | NoI | NoI | - | - | - | - |
| T42S | NoI | NoI | - | - | - | - |
| F43S | NoI | NoI | - | - | - | - |
| I132V | MiN | MiN | 980 (±60) | 280 (±40) | 1.1 | 2.4 |
| K136R | NoI | NP | 440 (±19) | 100 (±10) | 0.5 | 0.9 |
| F154Y | SN | SN | ND3 | ND | ND | ND |
| R155K | MeN | SN | 1830 (±240) | 1010 (±240) | 2.1 | 8.8 |
| T160A | NoI | NoI | - | - | - | - |
| D168G | MiN | MeN | 490 (±50) | 260 (±30) | 0.6 | 2.2 |
| D168E | NoI | NoI | - | - | - | - |
1
The table compares the in silico predictions of the impact of BSVs on ketoamide binding from the IRECS20 analysis, and corresponding EC50 values determined from H77S.3/GLuc2A-transfected cell cultures. Results shown represent the mean ± SD and fold changes (FC) compared to wild-type.
2
Predicted impact: NoI, no impact; MiN, minor negative impact, change only in a single ketoamide-BSV interaction (H-bond, van der Waals) or in polarity; MeN, moderate negative impact, combined changes in ketoamide-BSV interaction and polarity; SN, strong negative impact, same as for MeN but at particularly close ketoamide-BSV interaction sites; NP, not predictable;
3
ND, not determined.