Peer-reviewed veterinary case report
An Optimized Bioassay for Screening Combined Anticoronaviral Compounds for Efficacy against Feline Infectious Peritonitis Virus with Pharmacokinetic Analyses of GS-441524, Remdesivir, and Molnupiravir in Cats.
- Journal:
- Viruses
- Year:
- 2022
- Authors:
- Cook, Sarah et al.
- Affiliation:
- Department of Pathology · United States
- Species:
- cat
Plain-English summary
Feline infectious peritonitis (FIP) is a serious and often deadly disease in cats caused by a virus called feline infectious peritonitis virus (FIPV). There are two main forms of FIP: the "wet" form, which involves fluid buildup, and the "dry" form, which can affect the nervous system or eyes. This study looked at several antiviral medications to see how well they work against FIPV in the lab, both on their own and in combinations. The researchers found that certain combinations of these drugs showed promise in fighting the virus. They also tested how well the medications were absorbed in cats after giving them by mouth or through an injection, finding that the levels in the blood were effective for at least 24 hours.
Abstract
Feline infectious peritonitis (FIP) is a fatal disease of cats that currently lacks licensed and affordable vaccines or antiviral therapeutics. The disease has a spectrum of clinical presentations including an effusive ("wet") form and non-effusive ("dry") form, both of which may be complicated by neurologic or ocular involvement. The feline coronavirus (FCoV) biotype, termed feline infectious peritonitis virus (FIPV), is the etiologic agent of FIP. The objective of this study was to determine and compare the in vitro antiviral efficacies of the viral protease inhibitors GC376 and nirmatrelvir and the nucleoside analogs remdesivir (RDV), GS-441524, molnupiravir (MPV; EIDD-2801), and β-D-N-hydroxycytidine (NHC; EIDD-1931). These antiviral agents were functionally evaluated using an optimized in vitro bioassay system. Antivirals were assessed as monotherapies against FIPV serotypes I and II and as combined anticoronaviral therapies (CACT) against FIPV serotype II, which provided evidence for synergy for selected combinations. We also determined the pharmacokinetic properties of MPV, GS-441524, and RDV after oral administration to cats in vivo as well as after intravenous administration of RDV. We established that orally administered MPV at 10 mg/kg, GS-441524 and RDV at 25 mg/kg, and intravenously administered RDV at 7 mg/kg achieves plasma levels greater than the established corresponding ECvalues, which are sustained over 24 h for GS-441514 and RDV.
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Search related cases →Original publication: https://pubmed.ncbi.nlm.nih.gov/36366527/