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

被引:24
作者
Hawman, David W. [1 ]
Haddock, Elaine [1 ]
Meade-White, Kimberly [1 ]
Nardone, Glenn [2 ]
Feldmann, Friederike [1 ]
Hanley, Patrick W. [1 ]
Lovaglio, Jamie [1 ]
Scott, Dana [1 ]
Komeno, Takashi [3 ]
Nakajima, Nozomi [3 ]
Furuta, Yousuke [3 ]
Gowen, Brian B. [4 ]
Feldmann, Heinz [1 ]
机构
[1] NIAID, Rocky Mt Lab, NIH, Hamilton, MT 59840 USA
[2] NIAID, Res Technol Branch, NIH, Rockville, MD USA
[3] FUJIFILM Toyama Chem Co Ltd, Toyama, Japan
[4] Utah State Univ, Logan, UT 84322 USA
关键词
Crimean-Congo hemorrhagic Fever; Favipiravir; Antiviral; Macaques; EBOLA-VIRUS; RIBAVIRIN; PATHOGENESIS; INHIBITOR; MODEL;
D O I
10.1016/j.antiviral.2020.104858
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
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页数:6
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