Key binding locations of the de novo derivatives include Glu83 and Asp103 for H1, and Glu228 and Arg292 for N1. Mutations currently attributed to oseltamivir resistance are located at H275 and N295S of the NA [103] . Since the key binding locations of the TCM derivatives do not overlap with those causing oseltamivir resistance, derivatives will be able to bind to viruses that are currently resistant to TamifluH. In addition, the de novo derivatives do not bind to amino acids in H1 or N1 that are prone to mutation ( Table 6, Table 7 ) [40, 104] , thus would likely be able to exert activity across a range of mutant H1N1 viruses. Last but not the least, multiple bond formations observed in MD provide additional insurance against possible mutations at key binding residues. In the case of a single point mutation, the de novo compounds will remain bound to the H1 and N1 sites through another key residue, therefore resisting the development of drug resistance in the virus. Based on the results and observations of this study, the TCM de novo derivatives may be attractive compounds for designing novel dual-target inhibitors for H1 and N1. 