title: Characterization of susceptibility variants of influenza virus grown in the presence of T-705.
abstract: T-705 (favipiravir) is a potent inhibitor of RNA polymerases of influenza viruses. Susceptibility variants were isolated during passages in the presence of T-705. Nine variants with 0.4 to 2.1 times the 50% inhibitory concentration for plaque formation of the parent A/PR/8/34 (H1N1) strain had amino acid variations in the PB1, PB2, and PA genes of the RNA polymerase complex. However, the variation patterns in the RNA polymerase complex indicated that T-705 does not work as a mutagen, and resistant mutants were not isolated, possibly because a mutation leading to resistance would be lethal to the RNA polymerase function.
authors.affiliation: Department of Virology, University of Toyama, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Daikoku
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Tomoko
authors.initials: T
authors.lastname: Okuda
authors.forename: Kimiyasu
authors.initials: K
authors.lastname: Shiraki
mesh_terms: D000577:Amides / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D024882:Drug Resistance, Viral / Q000235:genetics; D005838:Genotype; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D009154:Mutation; D011719:Pyrazines / Q000494:pharmacology*; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000577:Amides; D000998:Antiviral Agents; D011719:Pyrazines; D014764:Viral Proteins; D012321:DNA-Directed RNA Polymerases; C462182:favipiravir