Table 1.
Sensitivity of BNM-III-170-resistant HIV-1 variants to inhibition by indoline CD4mcs
| HIV-1(AD8) Env variant | Fold resistance to: | IC50 (µM) | |||||
|---|---|---|---|---|---|---|---|
| BNM-III-170 (1) | CJF-III-288 (19) | CJF-IV-046 (30) | CJF-III-192 (26) | CJF-III-288 (19) | CJF-IV-046 (30) | CJF-III-192 (26) | |
| WT | 1 | 1 | 1 | 1 | 0.20 ± 0.03 | 0.20 ± 0.01 | 0.20 ± 0.01 |
| E64G | 109 | 25 | 20 | 32.5 | 5.0 ± 1.2 | 4.0 ± 2.0 | 6.5 ± 1.01 |
| S375N | 5.2 | 7.5 | 8.5 | 9 | 1.5 ± 0.17 | 1.7 ± 0.02 | 1.8 ± 0.91 |
| I424T | 5.2 | 11 | 8.5 | 9 | 2.2 ± 0.08 | 1.7 ± 0.02 | 1.8 ± 0.84 |
| E64G+S375N | >1,500 | 300 | 200 | 200 | 60.0 ± 7.2 | 40.0 ± 10.0 | 40.0 ± 5.0 |
| E64G+I424T | >1,500 | 375 | 200 | 200 | 75.0 ± 6.1 | 40.0 ± 12.2 | 40.0 ± 6.3 |
| S375N+I424T | 209 | 51 | 41 | 45 | 10.1 ± 2.2 | 8.2 ± 2.08 | 9.0 ± 3.0 |
| E64G+S375N+I424T | >1,500 | 1,450 | 700 | 650 | 290.2 ± 10 | 140.0 ± 15.0 | 130 ± 35.0 |
| 130-C | >1,500 | 1,305 | 700 | 400 | 260.9 ± 30 | 140.0 ± 20.7 | 80 ± 20.0 |
| A-MLV | >1,500 | >1,500 | >1,500 | >1,500 | >300 | >300 | >300 |
The sensitivity of recombinant luciferase-expressing viruses pseudotyped with the indicated HIV-1AD8 Env variants to the indoline CD4mcs was determined using Cf2Th-CD4/CCR5 target cells, as described in Materials and Methods. The IC50 values (in µM) are shown in the right three columns. The level of resistance relative to that of the wild-type (WT) AD8 Env is shown in the left columns; the values for the indane CD4mc, BNM-III-170, were derived from ref. 40.