The experimental procedures and screening results after each filtering step are summarized in Figure 1 . Among the 829 native TCM compounds, 81 docked into both H1 and N1 and were used for de novo evolution (Table S1 ). De novo compounds with dual binding capacities to H1 and N1 were ranked by combined DockScore and the top ten derivatives are listed in Table 1 . Nine of the ten top ranking de novo compounds were derived from Rosmaricine, a natural compound isolated from Rosemarinus officinalis [96] . The remaining de novo compound was based on Xylopine, which is naturally found in Guatteria amplifolia [97] .