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Comparison of Routes of Administration, Frequency, and Duration of Favipiravir Treatment in Mouse and Guinea Pig Models of Ebola Virus Disease

Journal Article · · Viruses
DOI:https://doi.org/10.3390/v16071101· OSTI ID:2471757
 [1];  [2];  [2];  [2];  [2];  [3];  [2];  [4];  [2];  [2];  [2];  [2];  [2];  [2];  [5]
  1. University of Texas Medical Branch, Galveston, TX (United States); Sandia National Laboratories (SNL-CA), Livermore, CA (United States)
  2. University of Texas Medical Branch, Galveston, TX (United States)
  3. Texas A&M University, College Station, TX (United States)
  4. Houston Methodist, Houston, TX (United States). Center for Molecular and Translational Human Infectious Diseases Research
  5. University of Texas Medical Branch, Galveston, TX (United States); Louisiana State University Health, Shreveport, LA (United States)
+ Show Author Affiliations
Favipiravir is a ribonucleoside analogue that has been explored as a therapeutic for the treatment of Ebola Virus Disease (EVD). Promising data from rodent models has informed nonhuman primate trials, as well as evaluation in patients during the 2013–2016 West African EVD outbreak of favipiravir treatment. However, mixed results from these studies hindered regulatory approval of favipiravir for the indication of EVD. This study examined the influence of route of administration, duration of treatment, and treatment schedule of favipiravir in immune competent mouse and guinea pig models using rodent-adapted Zaire ebolavirus (EBOV). A dose of 300 mg/kg/day of favipiravir with an 8-day treatment was found to be fully effective at preventing lethal EVD-like disease in BALB/c mice regardless of route of administration (oral, intraperitoneal, or subcutaneous) or whether it was provided as a once-daily dose or a twice-daily split dose. Preclinical data generated in guinea pigs demonstrates that an 8-day treatment of 300 mg/kg/day of favipiravir reduces mortality following EBOV challenge regardless of route of treatment or duration of treatments for 8, 11, or 15 days. This work supports the future translational development of favipiravir as an EVD therapeutic.
Research Organization:
Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States)
Sponsoring Organization:
National Institutes of Health (NIH); USDOE National Nuclear Security Administration (NNSA)
Grant/Contract Number:
NA0003525
OSTI ID:
2471757
Journal Information:
Viruses, Journal Name: Viruses Journal Issue: 7 Vol. 16; ISSN 1999-4915
Publisher:
MDPICopyright Statement
Country of Publication:
United States
Language:
English

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Related Subjects

60 APPLIED LIFE SCIENCES
EBOV
Ebola virus
T-705
Virology
animal model
favipiravir
filovirus