TABLE 2.
Anti-HIV-1 activities of enfuvirtide-CP conjugates EP40111 and EP40112 against various X4 and R5 HIV-1 strains and clades in PBMCs
| Compound | EC50 (nM)a |
||||||||
|---|---|---|---|---|---|---|---|---|---|
| NL4.3b (X4) | Ba-L (R5) | BZ167 (clade B, X4) | I-2496 (clade A, R5) | UG273 (clade A, R5) | US2 (clade B, R5) | ETH2220 (clade C, R5) | DJ259 (clade C, R5) | Mean for all strains and cladesd | |
| Enfuvirtide | 3.6 | 17.9 | 17.9 | 12.4 | 55.9 | 6.3 | 17.7 | 17.9 | 20 |
| EP40111 | 89.4 | 88.9 | 105.7 | 54.8 | 277.6 | 72.7 | 92.2 | 9.4 | 100 |
| EP40112 | 13.2 | 108.0 | 445.0 | 80.7 | 136.0 | 43.8 | 111.0 | 89.4 | 130 |
| AMD3100c | 3.6 | >1,000 | 18.5 | >1,000 | >1,000 | >1,000 | >1,000 | >1,000 | NCe |
| Maravirocc | >1,000 | 3.8 | >1,000 | 0.4 | 2.6 | 0.3 | 3.6 | 3.7 | NCe |
a
Representative values from several independent set of experiments in PBMCs from different donors.
b
The HIV-1 NL4.3 envelope sequence is identical to that of HIV-1 IIIB/LAI.
c
The CXCR4 antagonist (AMD3100) and the CCR5 antagonist (maraviroc) (kindly provided by G. Bridger, then at AnorMED, Langley, BC, Canada) were used as controls.
d
Mean values based on the EC50s obtained with all virus strains and clinical isolates.
e
NC, not calculated, since some EC50s were >1,000 nM.