Characterization of susceptibility variants of poliovirus grown in the presence of favipiravir

Tohru Daikoku, Mineyuki Mizuguchi, Takayuki Obita, Takeshi Yokoyama, Yoshihiro Yoshida, Masaya Takemoto, Kimiyasu Shiraki*

*この論文の責任著者

研究成果: ジャーナルへの寄稿学術論文査読

6 被引用数 (Scopus)

抄録

Background: T-705 (favipiravir) is a potent inhibitor of RNA-dependent RNA polymerases of influenza viruses and no favipiravir-resistant virus has been isolated. Poliovirus RNA polymerase has been well characterized and isolation of resistant virus was examined in poliovirus. Methods: Susceptibility variants of poliovirus I (Sabin strain) were isolated during passages in the presence of favipiravir and characterized for their susceptibility and the sequence of RNA polymerase. Results: Five variants with 0.47–1.88 times the 50% inhibitory concentration for plaque formation of the parent poliovirus had amino acid variations in the 3D gene of the RNA polymerase. The distribution of amino acid variations was not related to ribavirin resistance, and two amino acid variation sites were found near the finger domain. Conclusion: Favipiravir as a chain terminator would not be incorporated and replicate to cause lethal mutagenesis as a mutagen like ribavirin, and resistant mutants were not isolated. A high replication level would generate mutations leading to favipiravir resistance as ribavirin resistance was generated, but generated mutations would be lethal to the RNA polymerase function.

本文言語英語
ページ(範囲)581-586
ページ数6
ジャーナルJournal of Microbiology, Immunology and Infection
51
5
DOI
出版ステータス出版済み - 2018/10

ASJC Scopus 主題領域

  • 免疫アレルギー学
  • 免疫学および微生物学一般
  • 微生物学(医療)
  • 感染症

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