Characterization of Susceptibility Variants of Influenza Virus Grown in the Presence of T-705
Characterization of Susceptibility Variants of Influenza Virus Grown in the Presence of T-705
复制标题
DOI：
10.1254/jphs.14156sc
复制
发表时间：
2014-11-01
影响因子：
3.5
通讯作者：
Shiraki, Kimiyasu
中科院分区：
文献类型：
--
作者：
Daikoku, Tohru;Yoshida, Yoshihiro;Shiraki, Kimiyasu
T-705（法匹拉韦）是流感病毒 RNA 聚合酶的有效抑制剂。在 T-705 存在的情况下，在传代过程中分离出易感性变异。 9 个变体，其对亲本 A/PR/8/34 (H1N1) 菌株空斑形成的 50% 抑制浓度为 0.4 至 2.1 倍，其 RNA 聚合酶复合物的 PB1、PB2 和 PA 基因中存在氨基酸变异。然而，RNA聚合酶复合物的变异模式表明T-705不能作为诱变剂，并且没有分离出抗性突变体，可能是因为导致抗性的突变会对RNA聚合酶功能造成致命。
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.