title: Mapping mutations in influenza A virus resistant to norakin.
abstract: To elucidate the mode of action of norakin against influenza A virus we sequenced the hemagglutinin gene of 11 norakin-resistant mutants. Resistance was coupled with 1-3 amino acid exchanges. The majority of mutations was localized in the HA2 polypeptide and was mostly associated with changes in charge or polarity of the amino acids. The amino acid substitutions are discussed in the context of the 3D structure of X31 hemagglutinin considered to be representative of the influenza hemagglutinins. Most of the mutations appear to destabilize the pH 7.0 structure by distorting or destroying hydrogen bonds as well as salt-bridges which are responsible for intra- and intersubunit contacts, while others destabilize the location of the fusion peptide, facilitating conformational changes in the presence of the inhibitor.
authors.affiliation: Institute of Virology, Humboldt University, School of Medicine (Charité), Berlin, GDR.
authors.forename: S
authors.initials: S
authors.lastname: Prösch
authors.forename: H
authors.initials: H
authors.lastname: Heider
authors.forename: C
authors.initials: C
authors.lastname: Schroeder
authors.forename: A A
authors.initials: AA
authors.lastname: Shilov
authors.forename: B V
authors.initials: BV
authors.lastname: Sinitzyn
authors.forename: V M
authors.initials: VM
authors.lastname: Blinov
authors.forename: D H
authors.initials: DH
authors.lastname: Krüger
authors.forename: C
authors.initials: C
authors.lastname: Frömmel
mesh_terms: D000596:Amino Acids / Q000235:genetics; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002642:Chick Embryo; D002874:Chromosome Mapping; D004352:Drug Resistance, Microbial; D006388:Hemagglutinins / Q000235:genetics*; D009980:Influenza A virus / Q000187:drug effects / Q000235:genetics*; D009154:Mutation; D010880:Piperidines / Q000494:pharmacology*; D011487:Protein Conformation; D012367:RNA, Viral / Q000032:analysis
chemical_list: D000596:Amino Acids; D000998:Antiviral Agents; D006388:Hemagglutinins; D010880:Piperidines; D012367:RNA, Viral; C046667:triperiden