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

Autor: Johnson DM; Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.; Department of Biotechnology & Bioengineering, Sandia National Laboratories, Livermore, CA 945501, USA., Juelich T; Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA., Zhang L; Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA., Smith JK; Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA., Kalveram BK; Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA., Perez D; Office of Biosafety, Texas A&M University, College Station, TX 77843, USA., Smith J; Office of Regulated Nonclinical Studies, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA., Grimes MR; Center for Molecular and Translational Human Infectious Diseases Research, Houston Methodist, Houston, TX 77030, USA., Garron T; Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA., Torres M; Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA., Massey S; Office of Regulated Nonclinical Studies, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA., Brasel T; Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.; Office of Regulated Nonclinical Studies, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA., Beasley DWC; Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.; Office of Regulated Nonclinical Studies, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA., Freiberg AN; Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA., Comer JE; Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.; Office of Regulated Nonclinical Studies, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.
Jazyk: angličtina
Zdroj: Viruses [Viruses] 2024 Jul 09; Vol. 16 (7). Date of Electronic Publication: 2024 Jul 09.
DOI: 10.3390/v16071101
Abstrakt: 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.
Databáze: MEDLINE