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Effectiveness of favipiravir (T-705) against wild-type and oseltamivir-resistant influenza B virus in mice.
Virology ( IF 3.7 ) Pub Date : 2020-02-24 , DOI: 10.1016/j.virol.2020.02.005
Qiong-Qiong Fang 1 , Wei-Juan Huang 1 , Xi-Yan Li 1 , Yan-Hui Cheng 1 , Min-Ju Tan 1 , Jia Liu 1 , He-Jiang Wei 1 , Yao Meng 2 , Da-Yan Wang 1
Affiliation  

The emergence of resistant mutants to the wildly used neuraminidase inhibitors (NAIs) makes the development of novel drugs necessary. Favipiravir (T-705) is one of the RNA-dependent RNA polymerase (RdRp) inhibitors developed in recent years. To examine the efficacy of T-705 against influenza B virus infections in vivo, C57BL/6 mice infected with wild-type or oseltamivir-resistant influenza B/Memphis/20/96 viruses were treated with T-705. Starting 2 h post inoculation (hpi), T-705 was orally administered to mice BID at dosages of 50, 150, or 300 mg/kg/day for 5 days. Oseltamivir was used as control. Here, we showed that T-705 protected mice from lethal infection in a dose-dependent manner. T-705 administration also significantly reduced viral loads and suppressed pulmonary pathology. In addition, phenotypic assays demonstrated that no T-705-resistant viruses emerged after T-705 treatment. In conclusion, T-705 can be effective to protect mice from lethal infection with both wild-type and oseltamivir-resistant influenza B viruses.

中文翻译:

法维吡韦(T-705)对小鼠野生型和耐奥司他韦的乙型流感病毒的效力。

对野生使用的神经氨酸酶抑制剂(NAIs)的耐药突变体的出现使得开发新药成为必要。Favipiravir(T-705)是近年来开发的一种RNA依赖性RNA聚合酶(RdRp)抑制剂之一。为了检查T-705在体内对抗B型流感病毒的功效,用T-705处理感染了野生型或耐奥司他韦的B / Memphis / 20/96型流感病毒的C57BL / 6小鼠。接种后(hpi)2小时开始,以50、150或300 mg / kg / day的剂量对小鼠BID口服T-705,持续5天。奥司他韦用作对照。在这里,我们表明T-705以剂量依赖的方式保护小鼠免受致命感染。T-705给药还可以显着降低病毒载量并抑制肺部病理。此外,表型分析表明,在T-705治疗后没有出现T-705抗药性病毒。总之,T-705可有效保护小鼠免受野生型和耐奥司他韦的乙型流感病毒的致命感染。
更新日期:2020-02-24
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