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法匹拉韦(T-705)对野生型和奥司他韦耐药的乙型流感病毒在小鼠体内的有效性。

Effectiveness of favipiravir (T-705) against wild-type and oseltamivir-resistant influenza B virus in mice.

机构信息

Chinese National Influenza Center, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, WHO Collaborating Center for Reference and Research on Influenza, Beijing, 102206, China.

Chinese National Influenza Center, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, WHO Collaborating Center for Reference and Research on Influenza, Beijing, 102206, China.

出版信息

Virology. 2020 Jun;545:1-9. doi: 10.1016/j.virol.2020.02.005. Epub 2020 Feb 24.

Abstract

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.

摘要

抗广泛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物成为必要。法匹拉韦(T-705)是近年来开发的 RNA 依赖性 RNA 聚合酶(RdRp)抑制剂之一。为了研究 T-705 对体内乙型流感病毒感染的疗效,用 T-705 治疗感染野生型或奥司他韦耐药乙型流感/Memphis/20/96 病毒的 C57BL/6 小鼠。从接种后 2 小时(hpi)开始,将 T-705 以 50、150 或 300mg/kg/天的剂量每天口服 BID 给药 5 天。奥司他韦用作对照。在这里,我们表明 T-705 以剂量依赖性方式保护小鼠免受致死性感染。T-705 给药还显著降低了病毒载量并抑制了肺部病理学。此外,表型测定表明,在 T-705 治疗后没有出现 T-705 耐药病毒。总之,T-705 可以有效保护小鼠免受野生型和奥司他韦耐药乙型流感病毒的致死性感染。

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