To target Vif blue Vif red sA3G interfaces (Supplementary Materials / GraphycalAbstract.pse), screening to select the most appropriated 3D-molecular parents and their targeted cavities were performed by ADV blind-docking . First a library of 10 small molecules were selected from those previously described to bind Vif (antiVif) with anti-HIV activity. To maintain antiVif 2D geometries, their energies were minimized by the DW mmff94s+ force-field (Supplementary Materials / 10antiVif-mmff94s+.sdf). This DW force-field was required because other tested(gaff, uff, ghemical, mmff94 and mmff94s), altered the expected docked 2D structures and affinities of the resulting conformers (for instance, misplacing double carbon or nitrogen bonds and changing ring sizes). The antiVif mmff94s+ conformers (one per antiVif molecule) were then ADV docked using a 60x60x60 Å grid surrounding the whole Vif blue Vif red sA3G model (blind-docking). Blind-docking was preferred, because it predicts the best docking cavities, by selecting the conformers fitting them with the highest affinities. Among other possibilities, the resulting ADV blind-dockings predicted the highest affinities to Benzimidazole-26 (Vif8) and IMC15 (Vif4) . Both of them targeted the Vif red sA3G cavity interfaces (Supplementary Materials / 10antiVif.pse). Therefore, Vif8 and Vif4 were selected for further work.