Efficacy of favipiravir (T-705) against Crimean-Congo hemorrhagic fever virus infection in cynomolgus macaques
Efficacy of favipiravir (T-705) against Crimean-Congo hemorrhagic fever virus infection in cynomolgus macaques
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DOI：
10.1016/j.antiviral.2020.104858
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发表时间：
2020-09-01
影响因子：
7.6
通讯作者：
Feldmann, Heinz
中科院分区：
文献类型：
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作者：
Hawman, David W.;Haddock, Elaine;Feldmann, Heinz
克里米亚-刚果出血热病毒（CCHFV）是一种广泛分布于东欧、非洲、中东和亚洲的出血热病毒。它通过被感染的蜱虫叮咬、畜牧业传播，也可以在护理受感染患者的医疗环境中获得。在人类中，CCHFV可引起非特异性发热性疾病的突然发作，可迅速进展为严重的出血表现。目前，没有广泛可用的疫苗，虽然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，这表明需要更有效的抗病毒药物治疗CCHFV。法匹拉韦在日本获批用于治疗流感病毒感染，并显示出对其他高致病性RNA病毒（包括CCHFV）的前景，在I型干扰素缺陷小鼠模型中显示出疗效。在本报告中，我们利用食蟹猴模型评价了每日一次和每日两次法匹拉韦治疗对CCHFV感染的疗效。我们发现，当在感染后24小时开始治疗时，法匹拉韦治疗抑制了病毒血症和病毒脱落，并且法匹拉韦治疗动物中关键组织中的病毒负荷趋势较低。我们的数据表明，法匹拉韦在非人灵长类动物感染模型中对CCHFV具有体内有效性。
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.