TABLE 2.
Synthetic constructs with NS3 RAS observed in patient samples
| Subtype | Backbone | RAS(s) detected by deep sequencing (%) | NS3 SDM in construct | VOX EC50-fold change (mean ± SD) |
|---|---|---|---|---|
| 1a | H77 | R155K (65.7), I170V (>99) | R155K/I170V | 1.2 ± 0.3 |
| 1a | H77 | Q41K (1.5), Q80K (>99) | Q41K/Q80K | 2.8 ± 1.2 |
| 1a | H77 | F43L (1.1), Q80K (>99) | F43L/Q80K | 3.4 ± 0.62 |
| 1a | H77 | S122G (>99), R155K (3.0) | S122G/R155K | 6.2 ± 0.95 |
| 1a | H77 | Q80L (>99), D168E (57.4) | Q80L/D168E | 11 ± 2.2 |
| 1a | H77 | Q80K (98.7), D168Y (1.3) | Q80K/D168Y | 117 ± 13 |
| 1a | H77 | V55A (>99), D168E (3.6), I170V (1.5) | V55A/D168E/I170V | 1.5 ± 0.25 |
| 1a | H77 | Q41H (1.2), Q80K (>99), S122N (13.%) | Q41H/Q80K/S122N | 1.9 ± 0.33 |
| 1a | H77 | Q41H (10.1), Q80K (>99), S122G (4.9) | Q41H/Q80K/S122G | 2.0 ± 0.78 |
| 1a | H77 | V36M (>99), R155K (>99), I170V (57.9) | V36M/R155K/I170V | 3.6 ± 0.53 |
| 1a | H77 | S122G (3.0), R155K (29.2), I170V (65.6) | S122G/R155K/I170V | 5.2 ± 0.94 |
| 1a | H77 | T54S (86.8), V55I (87.3), Q80L (85.8) | T54S/V55I/Q80L | 7.0 ± 1.5 |
| 1a | H77 | Q80K (>99), D168E (51.4), I170V (>99) | Q80K/D168E/I170V | 8.0 ± 3.4 |
| 1a | H77 | S122R (>99), R155N (11.2), D168E (>99) | S122R/R155N/D168E | 11 ± 0.09 |
| 1a | H77 | T54S (>99), Y56H (1.6), I170V (>99) | T54S/Y56H/I170V | 11 ± 2.2 |
| 1a | H77 | T54S (29.5), V55A (3.6), Q80R (2.0), I170V (1.2) | T54S/V55A/Q80R/I170V | 1.3 ± 0.04 |
| 1a | H77 | V55A (>99), Q80R (92.8), D168E (98.4), I170V (98.3) | V55A/Q80R/D168E/I170V | 4.9 ± 0.06 |
| 1a | H77 | T54S (>99), V55I (16.2), S122G (1.1), R155K (81.3) | T54S/V55I/S122G/R155K | 5.9 ± 0.45 |
| 1a | H77 | T54S (>99), S122G (1.3), R155K (>99), I170V (1.1) | T54S/S122G/R155K/I170V | 9.2 ± 3.2 |
| 1a | H77 | Q41K (2.5), F43L (1.3), Q80K (98.9), D168Y (1.7) | Q41K/F43L/Q80K/D168Y | 233 ± 66 |
| 1a | H77 | T54S (>99), V55I (64.0), S122G (3.2), R155K (37.6), I170V (7.3) | T54S/V55I/S122G/R155K/I170V | 4.1 ± 0.95 |
| 1b | Con1 | D168N (1.0), V170I (>99) | D168N/V170I | 0.7 ± 0.01 |
| 1b | Con1 | Y56F (>99), D168Y (1.2) | Y56F/D168Y | 0.8 ± 0.03 |
| 1b | Con1 | Y56F (>99), Q80R (87.9) | Y56F/Q80R | 1.1 ± 0.41 |
| 1b | Con1 | Y56F (>99), V170I (95.9), V170T (2.1) | Y56F/V170T | 1.1 ± 0.09 |
| 1b | Con1 | Y56F (>99), V170I (95.9), V170T (2.1) | Y56F/V170I | 1.6 ± 0.48 |
| 1b | Con1 | Y56F (>99), S122N (1.0) | Y56F/S122N | 3.4 ± 0.62 |
| 1b | Con1 | Y56F (98.9), S122N (71.1), S122T (28.1), V170I (>99) | Y56F/S122T/V170I | 1.7 ± 0.02 |
| 1b | Con1 | Y56F (98.9), S122N (71.1), S122T (28.1), V170I (>99) | Y56F/S122N/V170I | 3.3 ± 0.36 |
| 2b | MD2b-1 | Y56F (>99), R122G (1.4) | Y56F/R122G | 0.9 ± 0.41 |
| 2b | MD2b-1 | L36M (1.6), F43L (3.1), G80V (1.9), G80W (2.1), R122L (1.5), R155M (2.3), R155S (2.1), D168Y (7.4), L175I (2.4) | L36M/F43L/G80W/R122L/R155M/D168Y/L175I | 0.8 ± 0.07 |
| 4a | Patient | F43S (1.7), Q80K (1.0), D168Y (1.1) | F43S/Q80K/D168Y | 1.0 ± 0.06 |
| 4d | Patient | R155Q (1.4), D168V (91.9) | R155Q/D168V | 1.0 ± 0.38 |
| 6a | Patient | L80K (98.2), D168E (>99) | L80K/D168E | 1.1a |
| 6a | Patient | V55A (1.1), L80K (>99), S122N (98.5) | V55A/L80K/S122N | 2.0 ± 0.04 |
a
EC50 value derived from a single experiment.