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法匹拉韦(T-705)对食蟹猴感染克里米亚-刚果出血热病毒的疗效。

Efficacy of favipiravir (T-705) against Crimean-Congo hemorrhagic fever virus infection in cynomolgus macaques.

机构信息

Rocky Mountain Laboratories, NIAID/NIH, Hamilton, MT, USA.

Rocky Mountain Laboratories, NIAID/NIH, Hamilton, MT, USA.

出版信息

Antiviral Res. 2020 Sep;181:104858. doi: 10.1016/j.antiviral.2020.104858. Epub 2020 Jul 6.

DOI:10.1016/j.antiviral.2020.104858
PMID:32645335
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11056077/
Abstract

Crimean-Congo hemorrhagic fever virus (CCHFV) is a widely distributed hemorrhagic fever virus found throughout Eastern Europe, Africa, the Middle East and Asia. It is spread through bites from infected ticks, animal husbandry and can also be acquired in the healthcare setting during care of infected patients. In humans, CCHFV can cause a sudden onset of a non-specific febrile illness that can rapidly progress to severe hemorrhagic manifestations. Currently, there is no widely available vaccine and although ribavirin has been suggested for the treatment of CCHFV, clinical efficacy in both animal models and humans is inconsistent suggesting more potent antivirals are needed for CCHFV. Favipiravir is approved in Japan for the treatment of influenza virus infections and has shown promise against other highly pathogenic RNA viruses including CCHFV with demonstrated efficacy in the type I interferon deficient mouse model. In this report we utilized the cynomolgus macaque model to evaluate the efficacy of once- and twice-daily favipiravir treatment against CCHFV infection. We found that favipiravir treatment suppressed viremia and viral shedding when treatment was initiated 24 h post-infection and viral burdens in key tissues trended lower in favipiravir-treated animals. Our data indicate that favipiravir has efficacy against CCHFV in vivo in a non-human primate model of infection.

摘要

克里米亚-刚果出血热病毒(CCHFV)是一种广泛分布的出血热病毒,存在于东欧、非洲、中东和亚洲。它通过受感染的蜱虫叮咬、畜牧业传播,也可以在医疗保健环境中接触受感染的患者时获得。在人类中,CCHFV 可引起突发的非特异性发热疾病,迅速进展为严重出血表现。目前,尚无广泛可用的疫苗,尽管利巴韦林已被建议用于治疗 CCHFV,但在动物模型和人类中的临床疗效不一致,表明需要更有效的抗病毒药物来治疗 CCHFV。法匹拉韦在日本被批准用于治疗流感病毒感染,并在包括 CCHFV 在内的其他高致病性 RNA 病毒方面显示出前景,在 I 型干扰素缺陷型小鼠模型中已证明具有疗效。在本报告中,我们利用食蟹猴模型来评估每日一次和两次法匹拉韦治疗对 CCHFV 感染的疗效。我们发现,法匹拉韦治疗在感染后 24 小时开始时抑制了病毒血症和病毒脱落,并且在法匹拉韦治疗的动物中关键组织中的病毒载量呈下降趋势。我们的数据表明,法匹拉韦在感染的非人类灵长类动物模型中具有针对 CCHFV 的体内疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b82b/11056077/9d4977a2cff3/nihms-1985942-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b82b/11056077/6883e435817a/nihms-1985942-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b82b/11056077/fc6a1b95204d/nihms-1985942-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b82b/11056077/9d4977a2cff3/nihms-1985942-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b82b/11056077/6883e435817a/nihms-1985942-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b82b/11056077/fc6a1b95204d/nihms-1985942-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b82b/11056077/9d4977a2cff3/nihms-1985942-f0003.jpg

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本文引用的文献

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Systematic Review and Meta-analysis of Postexposure Prophylaxis for Crimean-Congo Hemorrhagic Fever Virus among Healthcare Workers.系统评价和荟萃分析医护人员中克里米亚-刚果出血热病毒暴露后预防措施。
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Favipiravir (T-705) but not ribavirin is effective against two distinct strains of Crimean-Congo hemorrhagic fever virus in mice.
克里米亚-刚果出血热病毒复制子颗粒疫苗在恒河猴中是安全的,并能引发功能性、非中和性抗核蛋白抗体和T细胞活化。
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A replicating RNA vaccine confers protection in a rhesus macaque model of Crimean-Congo hemorrhagic fever.一种可复制的RNA疫苗在克里米亚-刚果出血热的恒河猴模型中提供保护。
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