TABLE 1.
Antiviral activity of T-20-derived peptides against T-20-resistant gp41 recombinant viruses
Anti-HIV activity was determined with the MAGI assay. The data shown are the mean values and S.D. that were obtained from the results of at least three independent experiments. Shown in parentheses are the -fold increases in resistance (increase in EC50 value) calculated by comparison to a reference virus. Increases of >10-fold are indicated in bold.
|
EC50
|
|||||||
|---|---|---|---|---|---|---|---|
| HIV-1WTa | HIV-1V38A | HIV-1N43D | HIV-1N43D/S138A | ||||
| nm | |||||||
| T-20 | 2.4 ± 0.6 | 23 ± 8.2 (9.6) | 49 ± 10 (20) | 84 ± 16 (35) | |||
| Small | |||||||
| T-20S138G | 1.3 ± 0.5 (0.5) | 65 ± 8.8 (27) | 141 ± 26 (59) | 185 ± 68 (77) | |||
| T-20S138A | 0.6 ± 0.1 (0.3) | 3.6 ± 1.7 (1.5) | 3.5 ± 0.9 (1.5) | 3.2 ± 1.0 (1.3) | |||
| Hydrophobic | |||||||
| T-20S138V | 0.4 ± 0.2 (0.2) | 31 ± 14 (13) | 22 ± 3.5 (9.2) | 23 ± 5.7 (9.6) | |||
| T-20S138L | 0.7 ± 0.1 (0.3) | 13 ± 6 (5.4) | 2.9 ± 0.7 (1.2) | 2.2 ± 0.4 (0.9) | |||
| T-20S138I | 0.5 ± 0.1 (0.2) | 4.9 ± 2 (2) | 2.9 ± 0.8 (1.2) | 2.4 ± 0.6 (1) | |||
| T-20S138M | 0.7 ± 0.2 (0.3) | 4.4 ± 0.1 (1.8) | 1.7 ± 0.5 (0.7) | 1.2 ± 0.4 (0.5) | |||
| T-20S138P | 446 ± 167 (186) | >1000 (>416) | >1000 (>416) | >1000 (>416) | |||
| Nucleophilic | |||||||
| T-20S138T | 0.9 ± 0.2 (0.4) | 39 ± 8.5 (16) | 161 ± 35 (67) | 124 ± 43 (52) | |||
| Aromatic | |||||||
| T-20S138F | 9.4 ± 2.6 (4) | 203 ± 89 (85) | 393 ± 119 (164) | 478 ± 116 (200) | |||
| T-20S138Y | 25 ± 9 (10) | 516 ± 223 (215) | >1000 (>416) | >1000 (>416) | |||
| T-20S138V | 29 ± 14 (12) | >1000 (>416) | >1000 (>416) | >1000 (>416) | |||
| Amide | |||||||
| T-20S138N | 19 ± 4 (8) | >1000 (>416) | >1000 (>416) | >1000 (>416) | |||
| T-20S138Q | 34 ± 11 (14) | >1000 (>416) | >1000 (>416) | >1000 (>416) | |||
| Acidic | |||||||
| T-20S138D | 210 ± 94 (88) | >1000 (>416) | >1000 (>416) | >1000 (>416) | |||
| T-20S138E | 283 ± 80 (118) | >1000 (>416) | >1000 (>416) | >1000 (>416) | |||
| Basic | |||||||
| T-20S138H | 210 ± 85 (88) | >1000 (>416) | >1000 (>416) | >1000 (>416) | |||
| T-20S138K | 708 ± 145 (295) | >1000 (>416) | >1000 (>416) | >1000 (>416) | |||
| T-20S138R | 362 ± 114 (150) | >1000 (>416) | >1000 (>416) | >1000 (>416) | |||
a
To improve the replication kinetics, D36G mutation, observed in the majority of HIV-1 strains, was introduced into the NL4-3 background used in this study (reference virus).