TABLE 1.
Inhibitory activity of fusion inhibitors against diverse primary HIV-1 isolates and drug-resistant mutantsa
| Pseudovirus | Subtype | Mean IC50 (nM) ± SD |
|||
|---|---|---|---|---|---|
| T-20 | 2P23 | LP-11 | LP-19 | ||
| Panel 1 primary viruses | |||||
| 92RW020 | A | 6.68 ± 1.15 | 1.96 ± 0.07 | 1.08 ± 0.18 | 0.39 ± 0.01 |
| 92UG037.8 | A | 9.88 ± 0.01 | 2.06 ± 0.43 | 1.04 ± 0.25 | 0.36 ± 0.03 |
| SF162 | B | 6.42 ± 0.13 | 17.52 ± 0.65 | 3.26 ± 0.77 | 0.69 ± 0.16 |
| JRFL | B | 29.3 ± 9.5 | 6.45 ± 1.1 | 2.7 ± 0.64 | 1.56 ± 0.27 |
| AC10.0.29 | B | 3.9 ± 1.08 | 1.36 ± 0.02 | 0.38 ± 0.07 | 0.17 ± 0.08 |
| SC422661.8 | B | 14.65 ± 2.35 | 2.21 ± 0.09 | 0.31 ± 0.08 | 0.1 ± 0.02 |
| B01 | B′ | 66.09 ± 9.23 | 6.2 ± 0.65 | 0.77 ± 0.19 | 0.22 ± 0.08 |
| B02 | B′ | 52.2 ± 10.91 | 8.57 ± 2.39 | 1.50 ± 0.44 | 0.49 ± 0.18 |
| B04 | B′ | 14.03 ± 4.77 | 4.75 ± 1.59 | 1.03 ± 0.12 | 0.31 ± 0.06 |
| CAP45.2.00.G3 | C | 176.24 ± 18.58 | 17.2 ± 3.6 | 1.61 ± 0.91 | 0.88 ± 0.25 |
| ZM109F.PB4 | C | 13.33 ± 4.9 | 1.07 ± 0.11 | 1 ± 0.28 | 0.37 ± 0.11 |
| ZM53M.PB12 | C | 33.68 ± 7.6 | 0.91 ± 0.04 | 0.69 ± 0.02 | 0.22 ± 0.08 |
| AE03 | A/E | 10.38 ± 7.47 | 4.74 ± 2.43 | 0.47 ± 0.15 | 0.32 ± 0.08 |
| AE04 | A/E | 18.32 ± 12.83 | 7.23 ± 2.21 | 0.98 ± 0.4 | 0.37 ± 0.18 |
| CH64.20 | B/C | 20.35 ± 1.88 | 0.54 ± 0.08 | 0.42 ± 0.17 | 0.14 ± 0.03 |
| CH070.1 | B/C | 159.45 ± 36.32 | 6.84 ± 1.04 | 3.18 ± 1.33 | 1.15 ± 0.13 |
| CH120.6 | B/C | 35.45 ± 9.03 | 9.69 ± 0.29 | 1.49 ± 0.54 | 0.83 ± 0.04 |
| Mean | 39.43 | 5.84 | 1.29 | 0.5 | |
| Panel 2 primary viruses | |||||
| 398-F1_F6_20 | A | 38.12 ± 4.62 | 1.43 ± 0.08 | 0.58 ± 0.22 | 0.11 ± 0.01 |
| TRO.11 | B | 14.24 ± 2.28 | 4.59 ± 1.08 | 3.07 ± 1.48 | 0.93 ± 0.08 |
| X2278_C2_B6 | B | 11.7 ± 1.99 | 1 ± 0.17 | 0.69 ± 0.02 | 0.13 ± 0.01 |
| CE703010217_B6 | C | 43.11 ± 9.81 | 5.20 ± 0.36 | 1.42 ± 0.19 | 0.4 ± 0.09 |
| CE1176_A3 | C | 10.9 ± 5.01 | 5.28 ± 0.31 | 1.46 ± 0.28 | 0.46 ± 0.1 |
| HIV_25710-2.43 | C | 20.12 ± 2.69 | 2.15 ± 0.33 | 0.7 ± 0.23 | 0.21 ± 0.1 |
| X1632-S2-B10 | G | 13.86 ± 2.57 | 4.64 ± 0.24 | 2.36 ± 0.61 | 0.99 ± 0.04 |
| 246_F3_C10_2 | A/C | 33.77 ± 7.54 | 4.13 ± 0.41 | 1.11 ± 0.26 | 0.33 ± 0.11 |
| CNE8 | A/E | 53.61 ± 6.38 | 11.94 ± 4.86 | 0.98 ± 0.16 | 0.38 ± 0.01 |
| CNE55 | A/E | 47.35 ± 23.37 | 3.25 ± 0.08 | 0.58 ± 0.18 | 0.25 ± 0.04 |
| CH119.10 | B/C | 6.82 ± 0.27 | 7.62 ± 0.6 | 1.35 ± 0.23 | 0.35 ± 0.1 |
| BJOX002000.03.2 | B/C | 22.21 ± 2.01 | 0.97 ± 0.14 | 1.24 ± 0.15 | 0.41 ± 0.1 |
| Mean | 26.32 | 4.35 | 1.3 | 0.41 | |
| T-20-resistant mutants | |||||
| NL4-3WT | B | 83.71 ± 9.56 | 0.72 ± 0.07 | 0.21 ± 0.01 | 0.12 ± 0.01 |
| NL4-3I37T | B | 559.02 ± 183.65 | 1.33 ± 0.12 | 0.52 ± 0.04 | 0.2 ± 0.07 |
| NL4-3V38A | B | 1,383.67 ± 137.65 | 0.81 ± 0.15 | 0.32 ± 0.09 | 0.15 ± 0.06 |
| NL4-3V38M | B | 774.8 ± 96.45 | 1.14 ± 0.19 | 0.42 ± 0.12 | 0.21 ± 0.01 |
| NL4-3Q40H | B | 1,910.34 ± 103.71 | 1.19 ± 0.12 | 0.28 ± 0.08 | 0.15 ± 0.07 |
| NL4-3N43K | B | 749.04 ± 157.25 | 1.19 ± 0.21 | 0.29 ± 0.07 | 0.15 ± 0.05 |
| NL4-3D36S/V38M | B | 423.45 ± 9.36 | 1.36 ± 0.33 | 0.63 ± 0.24 | 0.27 ± 0.06 |
| NL4-3I37T/N43K | B | 7,187 ± 4,941.26 | 1.28 ± 0.2 | 0.48 ± 0.14 | 0.22 ± 0.08 |
| NL4-3V38A/N42T | B | 3,167.67 ± 961.19 | 0.4 ± 0.06 | 0.14 ± 0.04 | 0.06 ± 0.02 |
| Mean | 1,804.3 | 1.05 | 0.37 | 0.17 | |
| HP23-resistant mutants | |||||
| NL4-3E49K | B | 176.7 ± 1.46 | 5.1 ± 0.51 | 0.44 ± 0.16 | 0.12 ± 0 |
| NL4-3L57R | B | 46.24 ± 11.17 | 39.62 ± 19.64 | 4.16 ± 1.05 | 0.43 ± 0.18 |
| NL4-3N126K | B | 209.87 ± 5.17 | 1.22 ± 0.61 | 0.67 ± 0.06 | 0.31 ± 0.03 |
| NL4-3E136G | B | 143.28 ± 77.63 | 4.68 ± 0.41 | 1.72 ± 0.84 | 0.62 ± 0.16 |
| NL4-3E49K/N126K | B | 190.03 ± 37.03 | 4.94 ± 0.48 | 2.7 ± 0.04 | 0.59 ± 0.04 |
| NL4-3L57R/E136G | B | 40.28 ± 12.6 | 168.49 ± 0.37 | 23.51 ± 3.57 | 2.76 ± 0.21 |
| Mean | 134.4 | 36.52 | 5.53 | 0.81 | |
a
The assay was performed in triplicate and repeated 3 times.