TABLE 3.
Ki values for the inhibition of PR mutants by clinically available inhibitors
| HIV-1 PR type (recombinant virus)a |
Ki (nM)b
|
||||||||
|---|---|---|---|---|---|---|---|---|---|
| SQV | RTV | IDV | NFV | LPV | APV | ATV | DRV | BCV | |
| Wild type | 0.04 ± 0.01 | 0.015 ± 0.003 | 0.12 ± 0.02 | 0.07 ± 0.01 | 0.018 ± 0.009 | 0.18 ± 0.02 | 0.024 ± 0.005 | 0.005 ± 0.003 | 0.0005 ± 0.002 |
| PR1 (VPR1) | 10.6 ± 0.9 (1.7) | 4.3 ± 0.3 (ND) | 87 ± 7 (23.9) | 13 ± 1 (52.3) | 8.2 ± 0.7 (2360) | 48.7 ± 2.9 (45.2) | 1.9 ± 0.2 (5) | 1.9 ± 0.3 (19.6) | 0.29 ± 0.04 (ND) |
| PR2 (VPR2) | 0.93 ± 0.16 (0.6) | 0.46 ± 0.03 (ND) | 30 ± 4.5 (9.7) | 13 ± 1.3 (11.8) | 0.83 ± 0.11 (688) | 10.4 ± 1.1 (26.2) | 0.43 ± 0.05 (2.3) | 0.68 ± 0.17 (2.1) | 0.11 ± 0.04 (ND) |
| PR3 (VPR3) | 84 ± 4 (20.8) | 67 ± 5 (ND) | 550 ± 30 (>55.5) | 62 ± 5 (>68) | 4.9 ± 0.4 (534) | 1.7 ± 0.05 (5.3) | 6.61 ± 0.56 (104) | 0.025 ± 0.011 (0.8) | 0.027 ± 0.015 (ND) |
| PR4 (VPR4) | 9.4 ± 1.4 (18) | 4.9 ± 0.4 (ND) | 102 ± 14 (>71.5) | 7.9 ± 0.6 (>85.3) | 0.47 ± 0.01 (72.3) | 0.5 ± 0.05 (5.1) | 1.6 ± 0.2 (82.4) | 0.027 ± 0.001 (1.1) | 0.012 ± 0.009 (ND) |
a
PR1 has the E35EE insertion, and PR3 carries the L33LL insertion.
b
Values are means ± standard deviations. The inhibition constants were determined by spectrophotometric assay at the pH optimum of HIV PR (pH 4.7). Numbers in parentheses show relative increases in IC50 values for the corresponding recombinant viruses VPR1 to VPR4 compared to the wild-type virus. These values were obtained by a multiple-cycle MTT recombinant virus assays. SQV, saquinavir; RTV, ritonavir; IDV, indinavir; NFV, nelfinavir; LPV, lopinavir; APV, amprenavir; ATV, atazanavir; DRV, darunavir; BCV, brecanavir; ND, not done.