title: Antiviral activity of stachyflin on influenza A viruses of different hemagglutinin subtypes.
abstract: BACKGROUND
  The hemagglutinin (HA) of influenza viruses is a possible target for antiviral drugs because of its key roles in the initiation of infection. Although it was found that a natural compound, Stachyflin, inhibited the growth of H1 and H2 but not H3 influenza viruses in MDCK cells, inhibitory activity of the compound has not been assessed against H4-H16 influenza viruses and the precise mechanism of inhibition has not been clarified.
  
  
  METHODS
  Inhibitory activity of Stachyflin against H4-H16 influenza viruses, as well as H1-H3 viruses was examined in MDCK cells. To identify factors responsible for the susceptibility of the viruses to this compound, Stachyflin-resistant viruses were selected in MDCK cells and used for computer docking simulation.
  
  
  RESULTS
  It was found that in addition to antiviral activity of Stachyflin against influenza viruses of H1 and H2 subtypes, it inhibited replication of viruses of H5 and H6 subtypes, as well as A(H1N1)pdm09 virus in MDCK cells. Stachyflin also inhibited the virus growth in the lungs of mice infected with A/WSN/1933 (H1N1) and A/chicken/Ibaraki/1/2005 (H5N2). Substitution of amino acid residues was found on the HA2 subunit of Stachyflin-resistant viruses. Docking simulation indicated that D37, K51, T107, and K121 are responsible for construction of the cavity for the binding of the compound. In addition, 3-dimensional structure of the cavity of the HA of Stachyflin-susceptible virus strains was different from that of insusceptible virus strains.
  
  
  CONCLUSIONS
  Antiviral activity of Stachyflin was found against A(H1N1)pdm09, H5, and H6 viruses, and identified a potential binding pocket for Stachyflin on the HA. The present results should provide us with useful information for the development of HA inhibitors with more effective and broader spectrum.
authors.affiliation: Department of Disease Control, Hokkaido University, Sapporo, Japan.
authors.forename: Yurie
authors.initials: Y
authors.lastname: Motohashi
authors.forename: Manabu
authors.initials: M
authors.lastname: Igarashi
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Okamatsu
authors.forename: Takeshi
authors.initials: T
authors.lastname: Noshi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sakoda
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Kimihito
authors.initials: K
authors.lastname: Ito
authors.forename: Ryu
authors.initials: R
authors.lastname: Yoshida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kida
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D004285:Dogs; D024882:Drug Resistance, Viral; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics; D009980:Influenza A virus / Q000187:drug effects* / Q000502:physiology; D008168:Lung / Q000821:virology; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D056004:Molecular Dynamics Simulation; D050505:Mutant Proteins / Q000235:genetics; D020125:Mutation, Missense; D009976:Orthomyxoviridae Infections / Q000188:drug therapy / Q000821:virology; D011485:Protein Binding; D011487:Protein Conformation; D012717:Sesquiterpenes / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D050505:Mutant Proteins; D012717:Sesquiterpenes; C120519:stachyflin