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

• Published in: Antiviral research Vol. 181; p. 104858
• Main Authors: Hawman, David W., Haddock, Elaine, Meade-White, Kimberly, Nardone, Glenn, Feldmann, Friederike, Hanley, Patrick W., Lovaglio, Jamie, Scott, Dana, Komeno, Takashi, Nakajima, Nozomi, Furuta, Yousuke, Gowen, Brian B., Feldmann, Heinz
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2020
• Subjects: Amides - therapeutic use; Animals; Antiviral; Antiviral Agents - therapeutic use; Crimean-Congo hemorrhagic Fever; Disease Models, Animal; Drug Administration Schedule; Favipiravir; Female; Hemorrhagic Fever Virus, Crimean-Congo - drug effects; Hemorrhagic Fever, Crimean - drug therapy; Macaca fascicularis - virology; Macaques; Male; Pyrazines - therapeutic use; Viral Load; Viremia - drug therapy; Virus Shedding - drug effects; Antiviral; Crimean-Congo hemorrhagic Fever; Macaques; Favipiravir
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2020.104858

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. •Once- or twice-daily favipiravir suppressed viremia and viral shedding in CCHFV infected macaques.•Viral loads within key tissues of favipiravir-treated animals trended lower than in placebo-treated animals.•Study highlights the importance of the macaque model of CCHF in evaluating antivirals for human CCHF cases.