TABLE 5.
Antiviral activities of the BDM-2 series against recombinant viruses constructed in NL4-3 background with amino acid polymorphisms at IN positions 124 and 125a
| Compound | Fold change in EC50 relative to parental NL4-3 in multiple-round infection of MT4 cells |
|||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| AA | AM | AT | AV | GT | GA | NA | NT | NV | SA | ST | TA | TM | TV | |
| DTG | 1 | 2 | 1 | 2 | 2 | 2 | 1 | 1 | 2 | 1 | 2 | 1 | 2 | 2 |
| BI-224436 | 1 | 0.4 | 1 | 1 | 2 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0.4 | 1 |
| S-I-82 | 1 | 1 | 1 | 2 | 3 | 3 | 10 | 5 | 5 | 4 | 2 | 2 | 1 | 1 |
| BDM-2 | 1 | 0.4 | 1 | 2 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0.3 | 1 |
| MUT871 | 1 | 0.4 | 1 | 1 | 2 | 3 | 2 | 1 | 1 | 1 | 1 | 1 | 0.3 | 1 |
| MUT872 | 1 | 0.3 | 1 | 0.5 | 2 | 2 | 1 | 1 | 1 | 1 | 1 | 1 | 0.2 | 1 |
| MUT884 | 0.4 | 0.2 | 1 | 0.5 | 2 | 1 | 2 | 1 | 1 | 1 | 1 | 1 | 0.2 | 1 |
| MUT916 | 1 | 0.2 | 0.5 | 0.4 | 1 | 1 | 4 | 1 | 0.4 | 1 | 1 | 1 | 0.2 | 0.4 |
a
The polymorphisms at IN amino acid positions 124/125 of the recombinant NL4-3 polymorphic viruses are indicated with two-letter codes (AA, AM, AT, AV, GT, GA, NA, NT, NV, SA, TA, TM, or TV). The levels of retained antiviral activity are reported by EC50 fold change compared to the wild type NL4-3 HIV-1 clone. Fold change values >10 highlighted in dark gray, and those in the range of 5 to 10 in light gray. One INSTI (DTG) and two INLAIs (BI-224436, S-I-82) were used as references. Data are mean ± SD of n > 5 independent experiments.