As shown in Fig. 1 , the rigid core2 fragment in Neo sticking out of the active pocket might not well adhere to the active pocket surface. To improve its binding affinity to the target protein, the bond C-N was cut off at the site shown in Fig. 2 . As a consequence of doing so, only the pyridine remained and the whole structural flexibility was enhanced so as to have the ability to stretch out to complement the surface of HA1 binding site.