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广谱抗病毒药物法匹拉韦可在疾病发作后保护豚鼠免受致死性拉沙病毒感染。

The broad-spectrum antiviral favipiravir protects guinea pigs from lethal Lassa virus infection post-disease onset.

作者信息

Safronetz David, Rosenke Kyle, Westover Jonna B, Martellaro Cynthia, Okumura Atsushi, Furuta Yousuke, Geisbert Joan, Saturday Greg, Komeno Takashi, Geisbert Thomas W, Feldmann Heinz, Gowen Brian B

机构信息

Laboratory of Virology, Division of Intramural Research, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.

Department of Animal, Diary, and Veterinary Sciences, Utah State University, Logan, Utah, United States of America.

出版信息

Sci Rep. 2015 Oct 12;5:14775. doi: 10.1038/srep14775.

Abstract

With up to 500,000 infections annually, Lassa virus (LASV), the cause of Lassa fever, is one of the most prevalent etiological agents of viral hemorrhagic fever (VHF) in humans. LASV is endemic in several West African countries with sporadic cases and prolonged outbreaks observed most commonly in Sierra Leone, Liberia, Guinea and Nigeria. Additionally several cases of Lassa fever have been imported into North America, Europe and Asia making LASV a global threat to public health. Despite this, currently no approved therapeutic or vaccine exists to treat or prevent LASV infections. Here, using a passaged strain of LASV that is uniformly lethal in Hartley guinea pigs, we demonstrate that favipiravir, a broad-spectrum antiviral agent and leading treatment option for influenza, has potent activity against LASV infection. In this model, once daily treatment with favipiravir significantly reduced viral titers in tissue samples and reduced mortality rates when compared with animals receiving vehicle-only or ribavirin, the current standard of care for Lassa fever. Favipiravir remained highly effective against lethal LASV infection when treatments were initiated nine days post-infection, a time when animals were demonstrating advanced signs of disease. These results support the further preclinical evaluation of favipiravir for Lassa fever and other VHFs.

摘要

拉沙病毒(LASV)是拉沙热的病原体,每年导致多达50万例感染,是人类病毒性出血热(VHF)最常见的病原体之一。拉沙病毒在西非几个国家呈地方性流行,在塞拉利昂、利比里亚、几内亚和尼日利亚最常出现散发病例和长期疫情。此外,北美、欧洲和亚洲均有输入性拉沙热病例,这使得拉沙病毒成为全球公共卫生威胁。尽管如此,目前尚无经批准用于治疗或预防拉沙病毒感染的疗法或疫苗。在此,我们使用一种在哈特利豚鼠中具有一致致死性的传代拉沙病毒株,证明了法匹拉韦(一种广谱抗病毒药物,也是治疗流感的主要选择)对拉沙病毒感染具有强大活性。在该模型中,与仅接受赋形剂或利巴韦林(拉沙热目前的标准治疗药物)的动物相比,每天一次用 法匹拉韦治疗可显著降低组织样本中的病毒滴度,并降低死亡率。当在感染后九天开始治疗时,法匹拉韦对致死性拉沙病毒感染仍非常有效,此时动物已表现出晚期疾病症状。这些结果支持对法匹拉韦用于拉沙热和其他病毒性出血热进行进一步的临床前评估。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9385/4600983/8b59aa7a6c3e/srep14775-f1.jpg

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