TABLE 4.
Frequencies of NS5A amino acid substitutions in cDNA clones isolated from BMS-790052-treated genotype 1a and 1b1a hybrid replicon cells
| Amino acid substitution | No. of clones at indicated BMS-790052 concn |
||||||
|---|---|---|---|---|---|---|---|
| 1a P1496L/S2204I cells |
1b1a100 S2204I cells |
||||||
| 200 pM | 1 nM | 1 μMa | Total | 200 pM | 1 nM | Total | |
| M28T | 5 | 4 | 9 | ||||
| ΔQ30 | 9 | 9 | |||||
| Q30E | 1 | 1 | 2 | 3 | 3 | ||
| Q30K | 1 | 1 | 2 | ||||
| Q30H | 4 | 5 | 9 | 3 | 3 | 6 | |
| Q30R | 5 | 4 | 9 | 3 | 3 | ||
| L31M | 3 | 3 | 3 | 5 | 8 | ||
| L31V | 1 | 1 | 2 | ||||
| P32L | 3 | 1 | 4 | ||||
| H54Y | 1 | 1 | |||||
| Y93C | 3 | 3 | 6 | 2 | 3 | 5 | |
| Y93H | 1 | 1 | 2 | 1 | 1 | 2 | |
| Y93N | 1 | 2 | 3 | ||||
| M28T + Q30H | 9 | 9 | |||||
| M28T + Q30L | 1 | 1 | |||||
| M28T + P32L | 3 | 3 | |||||
| M28T + Y93C | 1 | 1 | |||||
| M28T + Y93H | 3 | 3 | |||||
| M28T + Y93N | 1 | 1 | |||||
| Q30H + P32L | 3 | 3 | |||||
| Q30E + Y93C | 1 | 1 | |||||
| Q30E + Y93H | 1 | 1 | |||||
| Q30R + L31M | 2 | 2 | |||||
| Q30R + L31V | 2 | 2 | |||||
| Q30R + P32L | 1 | 1 | |||||
| Q30R + Y93H | 1 | 1 | |||||
| L31M + Y93C | 1 | 1 | |||||
| L31V + Y93H | 1 | 1 | |||||
| None | 1 | 1 | |||||
| Total | 29 | 20 | 42 | 91 | 16 | 13 | 29 |
a
Cells selected with 200 pM BMS-790052 were subsequently selected with 1 μM BMS-790052.