Binding site analysis, 3D-QSAR studies, and molecular design of flavonoids derivatives as potent neuraminidase inhibitors

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Binding site analysis of flavonoids derivatives indicated that Arg152, Trp178, Ile222, Glu227, and Ala246 were the key residues in the active pocket of 1nnc. Main influencing factors of interactions between flavonoids derivatives and neuraminidase (NA) were hydrogen bond and electrostatic. Meanwhile, 3D-QSAR models of flavonoids derivatives were constructed to understand chemical–biological interactions governing their activities toward NA. The developed 3D-QSAR models were robust and had good predictive capabilities. R2, Q2, Rtest2, and Qext2 of the CoMFA and CoMSIA models were 0.816 and 0.929, 0.607 and 0.750, 0.507 and 0.642, and 0.478 and 0.568, respectively. Moreover, hydrogen bonds and electrostatic factors highly contributed to inhibitory activity, which were unanimous in the docking results. In addition, based on the most active sample ID33, seven new compounds with high inhibitory activity and docking score were obtained.