Table 3. Effects of selected amino acid substitutions in pocket 1 of HIV-1 RT in the susceptibility to RMNC6 in RNase H and RDDP activity assays.
| RMNC6 | BTP | EFV | ||
|---|---|---|---|---|
| RT | RNase H | RDDP | RNase H | RDDP |
| IC50 (μM)a | IC50 (μM)b | IC50 (μM)a | IC50 (nM)b | |
| V106A | 5.3 ± 0.6 (4.1)c | 25.1 ± 2.3 (2.5) | 0.16 ± 0.03 (0.8) | 35.4 ± 2.2 (1.5) |
| V108A | 13.1 ± 2.5 (10) | 33.0 ± 5.2 (3.4) | 0.18 ± 0.04 (0.9) | 21.3 ± 3.6 (0.9) |
| Y188A | 3.3 ± 1.5 (2.5) | 20.9 ± 4.0 (2.1) | 0.19 ± 0.08 (1.0) | 28.3 ± 7.4 (1.2) |
| E224A | 7.9 ± 1.1 (6.1) | 13.8 ± 4.2 (1.4) | 0.15 ± 0.03 (0.8) | 24.9 ± 0.7 (1.1) |
| P225A | 1.7 ± 0.2 (1.3) | 3.1 ± 0.3 (0.3) | 0.13± 0.06 (0.7) | 19.5 ± 2.9 (0.8) |
| P226A | 1.9 ± 0.1 (1.5) | 18.9± 0.7 (1.9) | 0.29 ± 0.08 (1.5) | 18.9 ± 2.4 (0.9) |
| F227A | 0.7 ± 0.1 (0.5) | 15.2 ± 0.9 (1.5) | 0.22 ± 0.04 (1.2) | 61.5 ± 1.4 (2.7) |
| L228A | 1.5 ± 0.1 (1.1) | 13.1 ±1.9 (1.3) | 0.10 ± 0.06 (0.5) | 21.8 ± 3.8 (1.0) |
| W229A | 1.9 ± 0.5 (1.5) | 15.4 ± 2.8 (1.6) | 0.15 ± 0.08 (0.8) | 22.9 ± 5.2 (1.1) |
| M230A | 0.5 ± 0.1 (0.4) | 15.0 ± 3.5 (1.5) | 0.14 ± 0.04 (0.7) | 29.1 ± 2.2 (1.3) |
| G231A | 1.7 ± 0.4 (1.3) | 10.8 ± 2.4 (1.1) | 0.25 ± 0.03 (1.3) | 67.7 ±3.5 (2.9) |
aConcentration required to inhibit HIV-1 RT-associated RNase H activity by 50% obtained by three independent experiments (reported as average ± standard deviation).
bConcentration required to inhibit HIV-1 RT-associated RDDP activity by 50% obtained by three independent experiments (reported as average ± standard deviation).
cFold of increase with respect to wt RT.