Premium
Novel Dual‐Site‐Binding Neuraminidase Inhibitor from Virtual Screening by Pharmacophore and Molecular Dynamics Methods
Author(s) -
Huang Kun,
Wu Xiaowen,
Jiang Zhengyu,
Sun Haopeng,
You Qidong
Publication year - 2012
Publication title -
chinese journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.28
H-Index - 41
eISSN - 1614-7065
pISSN - 1001-604X
DOI - 10.1002/cjoc.201200313
Subject(s) - pharmacophore , neuraminidase , chemistry , virtual screening , binding site , computational biology , neuraminidase inhibitor , molecular dynamics , dual (grammatical number) , dock , active site , stereochemistry , combinatorial chemistry , biochemistry , enzyme , computational chemistry , biology , covid-19 , medicine , art , literature , disease , pathology , infectious disease (medical specialty)
Neuraminidase is a significant anti‐influenza target that plays crucial role in virus replication cycle. The discovery of 150‐cavity in Group‐1 neuraminidase provides us a novel mentality of designing inhibitor which can bind with both conserved site and 150‐cavity. In order to discover novel dual‐site‐binding inhibitors, a 3D chemical‐feature‐based pharmacophore model was established to cover dual‐site in neuraminidase. The dual‐site‐binding model was consistent in predicting the binding conformation of Group‐1 neuraminidase inhibitor and applied for virtual screening of Specs database. Compound 4 (ZINC05790048) that aligned well to the model was selected after multiple filtrations for molecular dynamics simulations, indicating improved binding energy with neuraminidase. It can sever as the lead compound for a novel series of inhibitors.