title: Homology modeling, docking, and molecular dynamics reveal HR1039 as a potent inhibitor of 2009 A(H1N1) influenza neuraminidase.
abstract: The neuraminidase of the influenza virus is the target of antiviral drugs oseltamivir and zanamivir. Clinical practices have shown that zanamivir and oseltamivir are effective in treating the 2009 A(H1N1) influenza virus. However, drug resistance strains are also emerging. Herein, we report the findings from homology modeling and molecular simulations of 2009 A(H1N1) neuraminidase complexed with zanamivir, oseltamivir, and several herb extracts with potential activities. Our docked oseltamivir and zanamivir results are consistent with previous studies. Based on the same procedure, the docked results of herb extracts HR1039 and HR1040 suggest that they are potential potent inhibitors of neuraminidase. Also, the binding modes of HR1039/HR1040 are different from those of oseltmivir and zanamivir, and may be effective in treating oseltamivir-resistant influenza virus strains.
authors.affiliation: National Center for High-Performance Computing, Hsin-Shi, Tainan County, Taiwan. c00jsw00@nchc.org.tw
authors.forename: Yeng-Tseng
authors.initials: YT
authors.lastname: Wang
authors.forename: Chen-Hsiung
authors.initials: CH
authors.lastname: Chan
authors.forename: Zhi-Yuan
authors.initials: ZY
authors.lastname: Su
authors.forename: Cheng-Lung
authors.initials: CL
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D004187:Disaccharides / Q000494:pharmacology*; D024882:Drug Resistance, Viral / Q000187:drug effects; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000201:enzymology*; D007251:Influenza, Human / Q000188:drug therapy; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D053139:Oseltamivir / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D016415:Sequence Alignment; D014315:Triterpenes / Q000494:pharmacology*; D053243:Zanamivir / Q000494:pharmacology
chemical_list: D004187:Disaccharides; C548871:HR 1039; D010936:Plant Extracts; D014315:Triterpenes; D053139:Oseltamivir; D009439:Neuraminidase; D053243:Zanamivir