Table 2. Antiviral activity of mCD4.2, mCD4.3 and mCD4-conjugates in comparison with mAb VRC01, b12 and the NNRTI dapivirine.
Viral strains | Clade-tropism | mCD4.2 (nM) | mCD4.2 PS1(nM) | mCD4.3 (nM) | mCD4.3PS1 (nM) | mAb VRC01 (nM) | mAb b12 (nM) | TMC120 Dapivirine (nM) |
---|---|---|---|---|---|---|---|---|
VI820 | A-X4R5 | 6.1 | 0.031 | 4.2 | 0.024 | 12 | >100 | 2 |
Bal | B-R5 | 2 | 0.035 | 2.3 | 0.031 | 0.64 | 1 | 1.7 |
IIIB | B-X4 | 0.22 | 0.0073 | 0.16 | 0.0025 | 0.64 | 0.09 | 0.84 |
MN | B-X4 | 0.59 | 0.046 | 0.37 | 0.026 | 2 | 1.5 | 1.5 |
SF162 | B-R5 | 1.3 | 0.01 | 0.66 | 0.0075 | 5.2 | 0.36 | 1.3 |
SHIV162P3 | B-R5 | 69 | 2.2 | 29 | 1.4 | 8.2 | 6 | >1000 |
pREJO.c/2864 cl2 | T/F B-R5 | 76 | 0.28 | 46 | 0.28 | 0.77 | >100 | 1.6 |
pTHRO.c/2626 | T/F B-R5 | 19 | 8.9 | 15 | 6.4 | >100 | 35 | 1.9 |
pWITO.c/2474 | T/F B-R5 | 184 | 1.3 | 178 | 1.5 | 2 | >100 | 1.1 |
VI829 | C-R5 | 512 | 4 | 221 | 3.6 | 9.3 | >100 | 1.3 |
P246F10 | T/F C-R5 | 718 | 58 | 510 | 33 | 85 | >100 | 1.4 |
pZM247Fv2 | T/F C-R5 | >1000 | 206 | >1000 | 192 | 5.7 | >100 | 2.3 |
VI824 | D-R5 | 56 | 0.68 | 39 | 0.7 | >100 | >100 | 1.2 |
VI1888 (CRF01) | AE-R5 | 5382 | 1064 | 4509 | 1212 | 16 | 80 | 2.1 |
Ca10-3 (CRF01) | AE-X4 | 4.7 | 0.12 | 3.1 | 0.076 | 13 | >100 | 1.2 |
MP568 (CRF02) | AG-R5 | 155 | 4.9 | 204 | 4.2 | 54 | >100 | 1.1 |
CC50 | 24036 | >50000 | 15540 | >50000 | >100 | >300 | 2524 |
Various replication competent HIV-1 or SHIV162P3 viruses at 10−3 MOI were incubated with a range of concentrations of the indicated compounds and TZM-bl cells for 48 h. Infection was determined as explained in the methods section. IC50 values (expressed in nM) represent the mean of at least 2 independent experiments, each with triplicate measurements and were calculated in GraphPad Prism 5.03 using non-linear regression. (T/F transmitted founder virus; X4: CXCR4 tropic; R5: CCR5 tropic, IC50: 50% inhibitory concentration; CC50: 50% cytotoxic concentration).