The nucleoside analog GS-441524 strongly inhibits feline infectious peritonitis (FIP) virus in tissue culture and experimental cat infection studies

Veterinary Microbiology
B G MurphyNiels C Pedersen

Abstract

Feline infectious peritonitis (FIP) is a common and highly lethal coronavirus disease of domestic cats. Recent studies of diseases caused by several RNA viruses in people and other species indicate that antiviral therapy may be effective against FIP in cats. The small molecule nucleoside analog GS-441524 is a molecular precursor to a pharmacologically active nucleoside triphosphate molecule. These analogs act as an alternative substrate and RNA-chain terminator of viral RNA dependent RNA polymerase. We determined that GS-441524 was non-toxic in feline cells at concentrations as high as 100 uM and effectively inhibited FIPV replication in cultured CRFK cells and in naturally infected feline peritoneal macrophages at concentrations as low as 1 uM. We determined the pharmacokinetics of GS-441524 in cats in vivo and established a dosage that would sustain effective blood levels for 24 h. In an experimental FIPV infection of cats, GS-441524 treatment caused a rapid reversal of disease signs and return to normality with as little as two weeks of treatment in 10/10 cats and with no apparent toxicity.

Citations

Feb 9, 2019·Journal, Genetic Engineering & Biotechnology·Romane A AwadAshraf G Attallah
Jun 11, 2020·Journal of Veterinary Diagnostic Investigation : Official Publication of the American Association of Veterinary Laboratory Diagnosticians, Inc·Laura SanglKatrin Hartmann
Jul 15, 2020·SLAS Discovery·Wei ZhuWei Zheng
Apr 1, 2020·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Bradley SanvilleStuart Cohen
Jan 16, 2020·Viruses·Javier A JaimesGary R Whittaker
May 17, 2019·Journal of Feline Medicine and Surgery·Diane AddieNicola Decaro
May 12, 2020·Frontiers in Microbiology·Longping V TseRalph S Baric
May 8, 2020·Biomedicines·Kenneth Lundstrom
Sep 29, 2020·Transboundary and Emerging Diseases·Saverio PaltrinieriStefania Lauzi
Nov 27, 2020·Microorganisms·Souvik Ghosh, Yashpal S Malik
Feb 2, 2021·Journal of Medicinal Chemistry·Yingjun LiXumu Zhang
Nov 17, 2020·Frontiers in Veterinary Science·Peter J Dickinson
Nov 4, 2020·The Veterinary Quarterly·Aaron M IzesMerran Govendir
Feb 8, 2021·European Journal of Medicinal Chemistry·Xia LinWeisen Lan
Feb 16, 2021·Frontiers in Medicine·Vikas BansalRahul Kashyap
Feb 16, 2021·Research in Veterinary Science·Giacomo RossiSara Mangiaterra
Mar 26, 2021·Frontiers in Pharmacology·Omkar IndariHem Chandra Jha
Apr 4, 2021·Pathogens·Magdalena Dunowska, Sayani Ghosh
Apr 9, 2021·Journal of Zoo and Wildlife Medicine : Official Publication of the American Association of Zoo Veterinarians·Alison E StoutGary R Whittaker
Apr 18, 2021·The Journal of Antimicrobial Chemotherapy·Andrew ReckersRoy Gerona
May 5, 2021·Antiviral Research·Zhao HuangGuihong Zhang
Jun 18, 2021·Critical Reviews in Analytical Chemistry·Sara I AborasMohamed A Korany
Jul 16, 2020·ACS Medicinal Chemistry Letters·Victoria C Yan, Florian L Muller
Aug 29, 2021·Viruses·Chao-Nan LinPeck Toung Ooi
Aug 28, 2021·Animals : an Open Access Journal From MDPI·Sarah JonesSamantha Evans
Jul 13, 2021·Antimicrobial Agents and Chemotherapy·Victoria C Yan, Florian L Muller
Sep 21, 2021·EcoHealth·Olivia S K ChanNathalie F Mauroo
Aug 25, 2020·Clinical Epidemiology and Global Health·Andri FrediansyahHarapan Harapan

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Datasets Mentioned

BETA
DQ010921

Methods Mentioned

BETA
PCR
in vitro transcription
density gradient centrifugation

Software Mentioned

PRISM
Origene
GraphPad

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