TABLE 1.
Resistance profiles of HIV-1 mutants to short-peptide fusion inhibitorsa
| HIV-1NL4-3 mutation | MTSC22 |
HP23 |
SC22EK |
|||
|---|---|---|---|---|---|---|
| IC50 (nM) | Fold change | IC50 (nM) | Fold change | IC50 (nM) | Fold change | |
| Wild type (WT) | 1.86 ± 0.13 | 1.00 | 0.41 ± 0.09 | 1.00 | 44.13 ± 5 | 1.00 |
| E49K | 73.75 ± 13.53 | 39.74 | 5.34 ± 0.18 | 13.19 | 1,723.5 ± 184.13 | 39.06 |
| L57R | 746.12 ± 57 | 402.08 | 230.05 ± 39.19 | 567.95 | 1,714.5 ± 385.06 | 38.86 |
| N126K | 4.27 ± 0.98 | 2.3 | 1.37 ± 0.17 | 3.39 | 151.93 ± 12.15 | 3.44 |
| E136G | 8.78 ± 1.03 | 4.73 | 2.89 ± 0.52 | 7.14 | 477.05 ± 42.53 | 10.81 |
| N163D | 2.03 ± 0.3 | 1.09 | 0.54 ± 0.05 | 1.32 | 46.85 ± 7.84 | 1.06 |
| E49K/L57R | 4,527.86 ± 585.46 | 2,440.06 | 1,371.3 ± 561.56 | 3,385.51 | 6,694.96 ± 1,036.29 | 151.73 |
| L57R/N126K | 345.2 ± 34.06 | 186.03 | 98.64 ± 5.92 | 243.53 | 644.12 ± 244.72 | 14.60 |
| L57R/E136G | 1,553.08 ± 535.22 | 836.96 | 679.55 ± 191.15 | 1,677.69 | 5,322.97 ± 1,529.45 | 120.63 |
| L57R/N163D | 608.95 ± 147.94 | 328.16 | 244.95 ± 55.18 | 604.74 | 4,014.67 ± 652.8 | 90.98 |
| E49K/L57R/N126K | 1,148.68 ± 145.24 | 619.02 | 542.17 ± 141.94 | 1,338.52 | 3,226.73 ± 955.88 | 73.13 |
| E49K/L57R/E136G | >7,500 | >4041.75 | >1,666.67 | >4114.73 | >7,500 | >169.97 |
| E49K/N126K/E136G/N163D (KKGD) | 359.22 ± 86.44 | 193.58 | 44.26 ± 3.08 | 109.26 | >7,500 | >169.97 |
| E49K/L57R/N126K/E136G (KRKG) | 2,249.37 ± 655.77 | 1,212.18 | 1,389.6 ± 250.15 | 3,430.69 | 7,054 ± 617.91 | 159.86 |
| E49K/L57R/N126K/N163D (KRKD) | 5,932.8 ± 331.89 | 3,197.18 | 983.12 ± 184.14 | 2,427.15 | 5,959.18 ± 447.45 | 135.05 |
| I37V/E49K/L57R/N126K/N163D (VKRKD) | 3,081.67 ± 212.92 | 1,660.71 | 1,096.38 ± 444.81 | 2,706.79 | 5,649.09 ± 686.21 | 128.02 |
| E49K/L57R/N126K/E136G/N163D (KRKGD) | 3,854.04 ± 533.69 | 2,076.94 | >1,666.67 | >4114.73 | 5,797.24 ± 596.92 | 131.38 |
a
Assay was performed in triplicate and repeated three times. Data are expressed as means ± standard deviations. IC50, 50% inhibitory concentration. The change in the IC50 was determined relative to the wild-type level.