title: [Design, synthesis and activity of a new type of influenza virus N1 neuraminidase inhibitors].
abstract: In this study, the "150-cavity", next to the H5N1 influenza virus neuraminidase activity site, has been used as the target to design and synthesize a structural analogue of chlorogenic acid, N-caffeoyl-GABA, using the flexible docking simulation. The docking study showed that the N-caffeoyl-GABA could be inserted into the "150-cavity" and combined with the Arg156 side chain by hydrogen bond. The best binding free energy of H5N1 NA-N-caffeoyl-GABA complex was -7.70 kcal mol(-1), equivalent that of the NA-oseltamivir. At the same time, using the H5N1 pseudotyping virus-based NA inhibitors screening model, we determined the inhibitory effect of oseltamivir, chlorogenic acid and N-caffeoyl-GABA on the NA. Compared with chlorogenic acid, N-caffeoyl-GABA significantly enhanced the inhibitory effect on NA, but less than oseltamivir. This study showed that the "150-cavity" could possibly be used as a new neuraminidase inhibitors target, and provided a path for the development of new neuraminidase inhibitors.
authors.affiliation: Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang 443002, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.forename: Lei
authors.initials: L
authors.lastname: Jin
authors.forename: Nian-yu
authors.initials: NY
authors.lastname: Huang
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.forename: Hua-jun
authors.initials: HJ
authors.lastname: Luo
authors.forename: Jian-feng
authors.initials: JF
authors.lastname: Chen
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002109:Caffeic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000201:enzymology*; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D000998:Antiviral Agents; D002109:Caffeic Acids; D004791:Enzyme Inhibitors; C053362:N-caffeoyl-4-aminobutyric acid; D005680:gamma-Aminobutyric Acid; D009439:Neuraminidase