title: Docking and 3D QSAR study of thiourea analogs as potent inhibitors of influenza virus neuraminidase.
abstract: Surflex-Dock was applied to study interactions between 30 thiourea analogs and neuraminidase (NA). The docking results showed that hydrogen bonding and electrostatic interactions were highly correlated with the activities of neuraminidase inhibitors (NIs), followed by hydrophobic and steric factors. Moreover, there was a strong correlation between the predicted binding affinity (total score) and experimental pIC₅₀ (correlation coefficient r = 0.870; P < 0.0001). A three dimensional holographic vector of atomic interaction field (3D-HoVAIF) was employed to construct a QSAR model. The r², q² and r² (test) values of the optimal QSAR model were 0.849, 0.724 and 0.689, respectively. From the QSAR model, it could be seen that electrostatic, hydrophobic and steric interactions were closely related to inhibitory activity, which was consistent with the docking results. Based on the docking and QSAR results, five new compounds with high predicted activities were designed.
authors.affiliation: College of Bioengineering, Chongqing University, Chongqing 400044, China. wy7472@126.com
authors.forename: Jiaying
authors.initials: J
authors.lastname: Sun
authors.forename: Shaoxi
authors.initials: S
authors.lastname: Cai
authors.forename: Hu
authors.initials: H
authors.lastname: Mei
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Ning
authors.initials: N
authors.lastname: Yan
authors.forename: Yuanqiang
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D003198:Computer Simulation; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D015394:Molecular Structure; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D009975:Orthomyxoviridae / Q000201:enzymology; D011485:Protein Binding; D011487:Protein Conformation; D021281:Quantitative Structure-Activity Relationship; D055672:Static Electricity; D013890:Thiourea / Q000031:analogs & derivatives*
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D009439:Neuraminidase; D013890:Thiourea