title: Predicting dual-targeting anti-influenza agents using multi-models.
abstract: Influenza is an acute respiratory infectious disease caused by influenza viruses. Its subtype can be distinguished based on the antigenicity of two surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA). One of the main challenges in anti-influenza drug development is the quick evolution of drug resistance due to virus mutations. One solution to this problem is to develop dual-targeting anti-influenza agents. In this paper, a new rationally designed virtual screening protocol that combines structure-based approaches (molecular docking and molecular dynamic simulations) and ligand-based approaches (support vector machines and 3D shape & electrostatic similarity algorithms) is reported for the virtual screening of dual-targeting agents against HA and NA. The final hits came from the consensus of the ligand- and receptor-based knowledge of HA and NA and were tested using ADMET predictions. Evidence from the binding energy calculations and binding mode analyses suggested that several of the hits are promising as dual-targeting anti-influenza agents. The virtual screening protocol may also lead to the identification of innovative drugs in other fields.
authors.affiliation: School of Pharmaceutical Sciences & Institute of Human Virology, Sun Yat-Sen University, 132 East Circle Road at University City, Guangzhou, 510006, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Hu
authors.initials: H
authors.lastname: Ge
authors.forename: Yali
authors.initials: Y
authors.lastname: Li
authors.forename: Yufang
authors.initials: Y
authors.lastname: Xie
authors.forename: Yingyan
authors.initials: Y
authors.lastname: He
authors.forename: Mengyan
authors.initials: M
authors.lastname: Xu
authors.forename: Qiong
authors.initials: Q
authors.lastname: Gu
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry* / Q000627:therapeutic use; D055808:Drug Discovery / Q000379:methods*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype; D007251:Influenza, Human / Q000188:drug therapy / Q000821:virology; D056004:Molecular Dynamics Simulation; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D060388:Support Vector Machine; D014764:Viral Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D014764:Viral Proteins; C483468:hemagglutinin, human influenza A virus; C487630:NA protein, influenza A virus; D009439:Neuraminidase