Broad spectrum antiviral activity of favipiravir (T-705): protection from highly lethal inhalational Rift Valley Fever.
Broad spectrum antiviral activity of favipiravir (T-705): protection from highly lethal inhalational Rift Valley Fever.
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DOI：
10.1371/journal.pntd.0002790
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发表时间：
2014-04
影响因子：
3.8
通讯作者：
Hartman AL
中科院分区：
文献类型：
--
作者：
Caroline AL;Powell DS;Bethel LM;Oury TD;Reed DS;Hartman AL
开发对多种病毒感染具有广谱活性的抗病毒药物将大有裨益。由于对目前许可的抗病毒药物的耐药性的演变，正在开发新的抗流感药物，包括目前正在进行人体临床试验的Favipiravir （T-705）。T-705对包括裂谷热病毒（RVFV）在内的多种病毒显示出广谱的体外活性。裂谷热是一种被忽视的重要热带病，在流行地区造成人类、农业和经济损失。裂谷热有可能在新的地点出现，并构成潜在的生物恐怖主义威胁。在本研究中，通过气溶胶途径对感染RVFV毒力强的ZH501株Wistar-Furth大鼠进行T-705的体内疗效评价。Wistar-Furth大鼠在经肠外或吸入暴露于致病性ZH501裂谷热病毒毒株后极易患上一种迅速致死的疾病。在目前的研究中，进行了两个实验：剂量测定研究和延迟治疗研究。在这两个实验中，所有未经治疗的对照大鼠都死于疾病。在感染裂谷热病毒并用T-705治疗的72只大鼠中，只有6只死于疾病。其余66只大鼠（92%）在致命感染中幸存下来，没有明显的体重减轻或发烧。治疗后死亡的6只大鼠在死于脑病之前存活时间明显延长。目前，还没有获得许可的治疗裂谷热的抗病毒药物。在这里，T-705在裂谷热高致死大鼠模型中显示出显著的疗效，即使在感染后48小时给予。这是第一个显示感染了致病性ZH501裂谷热病毒毒株的大鼠具有保护作用的研究。我们的数据表明，T-705有潜力成为一种广谱抗病毒药物。广谱抗病毒药物是首选，因为它们有能力治疗一系列病毒性疾病，而不仅仅是一种。在进行人体临床试验时，由于伦理和后勤方面的考虑，美国食品和药物管理局（FDA）很难批准用于治疗被忽视的热带病的抗病毒药物。裂谷热是一种地方性热带疾病，可导致人类发病和死亡，并对畜牧业造成经济损失。目前还没有获得许可的治疗裂谷热的抗病毒药物。在这项研究中，我们发现一种新的抗流感药物Favipiravir （T-705）能够在大鼠中预防致死性裂谷热，因此有望成为一种广谱抗病毒治疗药物。
Development of antiviral drugs that have broad-spectrum activity against a number of viral infections would be of significant benefit. Due to the evolution of resistance to currently licensed antiviral drugs, development of novel anti-influenza drugs is in progress, including Favipiravir (T-705), which is currently in human clinical trials. T-705 displays broad-spectrum in vitro activity against a number of viruses, including Rift Valley Fever virus (RVFV). RVF is an important neglected tropical disease that causes human, agricultural, and economic losses in endemic regions. RVF has the capacity to emerge in new locations and also presents a potential bioterrorism threat. In the current study, the in vivo efficacy of T-705 was evaluated in Wistar-Furth rats infected with the virulent ZH501 strain of RVFV by the aerosol route. Wistar-Furth rats are highly susceptible to a rapidly lethal disease after parenteral or inhalational exposure to the pathogenic ZH501 strain of RVFV. In the current study, two experiments were performed: a dose-determination study and a delayed-treatment study. In both experiments, all untreated control rats succumbed to disease. Out of 72 total rats infected with RVFV and treated with T-705, only 6 succumbed to disease. The remaining 66 rats (92%) survived lethal infection with no significant weight loss or fever. The 6 treated rats that succumbed survived significantly longer before succumbing to encephalitic disease. Currently, there are no licensed antiviral drugs for treating RVF. Here, T-705 showed remarkable efficacy in a highly lethal rat model of Rift Valley Fever, even when given up to 48 hours post-infection. This is the first study to show protection of rats infected with the pathogenic ZH501 strain of RVFV. Our data suggest that T-705 has potential to be a broad-spectrum antiviral drug. Broad-spectrum antiviral drugs are preferred because they have the capacity to treat a range of viral illnesses rather than just one. Food and Drug Administration (FDA) approval of antiviral drugs to treat neglected tropical diseases is difficult to obtain due to ethical and logistical considerations when conducting human clinical trials. Rift Valley Fever (RVF) is an endemic tropical disease that causes human morbidity and mortality, as well as economic damage to the livestock industry. There are no licensed antiviral drugs to treat RVF. In this study, we found that a novel anti-influenza drug, Favipiravir (T-705), is able to prevent lethal RVF in rats, and therefore shows promise as a broad-spectrum antiviral treatment.
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影响因子：
3.7
作者：
Gowen BB;Smee DF;Wong MH;Hall JO;Jung KH;Bailey KW;Stevens JR;Furuta Y;Morrey JD
通讯作者：
Morrey JD
影响因子：
3.8
作者：
ANDERSON, GW;SLONE, TW;PETERS, CJ
通讯作者：
PETERS, CJ
影响因子：
3.8
作者：
ANDERSON, GW;PETERS, CJ
通讯作者：
PETERS, CJ
影响因子：
11.8
作者：
Hartley DM;Rinderknecht JL;Nipp TL;Clarke NP;Snowder GD;National Center for Foreign Animal and Zoonotic Disease Defense Advisory Group on Rift Valley Fever
通讯作者：
National Center for Foreign Animal and Zoonotic Disease Defense Advisory Group on Rift Valley Fever
影响因子：
5.5
作者：
ANDERSON, GW;LEE, JO;MEADORS, G
通讯作者：
MEADORS, G