title: Novel inhibitor design for hemagglutinin against H1N1 influenza virus by core hopping method.
abstract: The worldwide spread of H1N1 avian influenza and the increasing reports about its resistance to the current drugs have made a high priority for developing new anti-influenza drugs. Owing to its unique function in assisting viruses to bind the cellular surface, a key step for them to subsequently penetrate into the infected cell, hemagglutinin (HA) has become one of the main targets for drug design against influenza virus. To develop potent HA inhibitors, the ZINC fragment database was searched for finding the optimal compound with the core hopping technique. As a result, the Neo6 compound was obtained. It has been shown through the subsequent molecular docking studies and molecular dynamic simulations that Neo6 not only assumes more favorable conformation at the binding pocket of HA but also has stronger binding interaction with its receptor. Accordingly, Neo6 may become a promising candidate for developing new and more powerful drugs for treating influenza. Or at the very least, the findings reported here may provide useful insights to stimulate new strategy in this area.
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin, China.
authors.forename: Xiao-Bo
authors.initials: XB
authors.lastname: Li
authors.forename: Shu-Qing
authors.initials: SQ
authors.lastname: Wang
authors.forename: Wei-Ren
authors.initials: WR
authors.lastname: Xu
authors.forename: Run-Ling
authors.initials: RL
authors.lastname: Wang
authors.forename: Kuo-Chen
authors.initials: KC
authors.lastname: Chou
mesh_terms: D000465:Algorithms; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000378:metabolism*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects*; D007251:Influenza, Human / Q000821:virology*; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D014584:User-Computer Interface
chemical_list: D000998:Antiviral Agents; D019267:Hemagglutinin Glycoproteins, Influenza Virus