TABLE 2.
Effect of MTSC22-induced mutations on the sensitivity of first- and next-generation fusion inhibitorsa
| HIV-1NL4-3 mutation | T20 |
C34 |
SFT |
|||
|---|---|---|---|---|---|---|
| IC50 (nM) | Fold change | IC50 (nM) | Fold change | IC50 (nM) | Fold change | |
| Wild-type (WT) | 81.77 ± 3.99 | 1.00 | 1.49 ± 0.25 | 1.00 | 1.87 ± 0.13 | 1.00 |
| E49K | 222.84 ± 13.24 | 2.73 | 4.76 ± 1.73 | 3.20 | 4.84 ± 0.46 | 2.59 |
| L57R | 42.85 ± 4.4 | 0.52 | 1.13 ± 0.15 | 0.76 | 1.04 ± 0.18 | 0.56 |
| N126K | 184.63 ± 18.32 | 2.26 | 3.52 ± 0.2 | 2.37 | 5.36 ± 2.87 | 2.87 |
| E136G | 175.68 ± 51.11 | 2.15 | 7.8 ± 1.3 | 5.25 | 9.62 ± 3.77 | 5.15 |
| N163D | 104.86 ± 50.14 | 1.28 | 1.97 ± 0.3 | 1.32 | 2.15 ± 0.17 | 1.15 |
| E49K/L57R | 18.75 ± 6.29 | 0.23 | 1.98 ± 0.31 | 1.33 | 1.6 ± 0.48 | 0.86 |
| L57R/N126K | 17.83 ± 4.24 | 0.22 | 1 ± 0.15 | 0.67 | 0.74 ± 0.1 | 0.40 |
| L57R/E136G | 34.18 ± 4.08 | 0.42 | 4.78 ± 0.61 | 3.21 | 4.02 ± 1.02 | 2.15 |
| L57R/N163D | 51.76 ± 7.11 | 0.63 | 2.54 ± 0.2 | 1.71 | 1.84 ± 0.63 | 0.99 |
| E49K/L57R/N126K | 10.59 ± 0.47 | 0.13 | 2.34 ± 0.25 | 1.57 | 0.85 ± 0.25 | 0.46 |
| E49K/L57R/E136G | 13.64 ± 2 | 0.17 | 6.2 ± 2.19 | 4.17 | 4.76 ± 1.43 | 2.55 |
| E49K/N126K/E136G/N163D (KKGD) | 477.43 ± 89.13 | 5.84 | 32.99 ± 1.99 | 22.18 | 32.96 ± 2.91 | 17.67 |
| E49K/L57R/N126K/E136G (KRKG) | 10.71 ± 1.1 | 0.13 | 3.87 ± 0.55 | 2.61 | 1.55 ± 0.14 | 0.83 |
| E49K/L57R/N126K/N163D (KRKD) | 12.35 ± 3.05 | 0.15 | 3.14 ± 0.65 | 2.11 | 0.93 ± 0.09 | 0.50 |
| I37V/E49K/L57R/N126K/N163D (VKRKD) | 29.38 ± 1.28 | 0.36 | 3.7 ± 0.67 | 2.49 | 1.41 ± 0.07 | 0.75 |
| E49K/L57R/N126K/E136G/N163D (KRKGD) | 12.22 ± 2.52 | 0.15 | 14.39 ± 2.6 | 9.68 | 3.05 ± 0.07 | 1.63 |
a
The 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.