Docking and 3D-QSAR investigations of pyrrolidine derivatives as potent neuraminidase inhibitors


Corresponding author: Jiaying Sun,


Docking studies of pyrrolidine derivatives indicated that Trp178, Arg371, and Tyr406 were the key residues in the active pocket of influenza neuraminidase (NA). Hydrogen bond and electrostatic factors mainly influenced interactions between pyrrolidine derivatives and NA. Moreover, there was a significant correlation between binding affinity (total scores) and the experimental pIC50. Meanwhile, 3D-QSAR models of 87 pyrrolidine derivatives were developed to understand chemical–biological interactions governing their activities toward NA. Furthermore, R2, Q2, inline image, and inline image of the models were from 0.731 to 0.830, from 0.560 to 0.611, from 0.762 to 0.875, and from 0.649 to 0.856, respectively. QSAR modeling results elucidated that hydrogen bonds and electrostatic factors highly contributed to inhibitory activity, which was unanimous in the docking results.