Due to the lack of reported H1 ligand bioactivities in the literature, direct assessment of bioactivity through construction of CoMFA and CoMSIA models was not possible. Alternatively, indirect support was provided by assessing the ability of de novo derivatives to maintain contour to the N1 CoMFA/CoMSIA maps while forming interactions at key residues in H1, Glu83 and Asp103 [92] . As illustrated in Figure 12 the TCM de novo derivatives docked into the H1 binding site and formed critical interactions at Glu83 and Asp103 without losing contour to the CoMFA and CoMSIA maps. These results suggest that not only were the TCM de novo derivatives capable of docking into both H1 and N1, but that biological activity was also predicted in both binding sites, thus it is possible to develop dual-targeting drugs from the selected de novo derivatives.