Characterization of amino acid substitutions in feline coronavirus 3C-like protease from a cat with feline infectious peritonitis treated with a protease inhibitor.
Amino Acid Sequence
Animals
Base Sequence
Binding Sites
Cat Diseases
/ virology
Cats
Coronaviridae Infections
/ drug therapy
Coronavirus, Feline
/ enzymology
Feline Infectious Peritonitis
/ complications
Male
Models, Molecular
Protease Inhibitors
/ pharmacology
Protein Conformation
Pyrrolidines
/ pharmacology
RNA, Viral
Sequence Alignment
Sulfonic Acids
Viral Proteins
/ chemistry
3C-like protease
Antivirals
Feline coronavirus
Feline infectious peritonitis virus
Genetic barrier
Resistance
Journal
Veterinary microbiology
ISSN: 1873-2542
Titre abrégé: Vet Microbiol
Pays: Netherlands
ID NLM: 7705469
Informations de publication
Date de publication:
Oct 2019
Oct 2019
Historique:
received:
10
07
2019
revised:
21
08
2019
accepted:
21
08
2019
entrez:
6
10
2019
pubmed:
6
10
2019
medline:
29
1
2020
Statut:
ppublish
Résumé
Feline infectious peritonitis (FIP) is a highly fatal disease caused by a virulent feline coronavirus in domestic and wild cats. We have previously reported the synthesis of potent coronavirus 3C-like protease (3CLpro) inhibitors and the efficacy of a protease inhibitor, GC376, in client-owned cats with FIP. In this study, we studied the effect of the amino acid changes in 3CLpro of feline coronavirus from a feline patient who received antiviral treatment for prolonged duration. We generated recombinant 3CLpro containing the identified amino acid changes (N25S, A252S or K260 N) and determined their susceptibility to protease inhibitors in the fluorescence resonance energy transfer assay. The assay showed that N25S in 3CLpro confers a small change (up to 1.68-fold increase in the 50% inhibitory concentration) in susceptibility to GC376, but other amino acid changes do not affect susceptibility. Modelling of 3CLpro carrying the amino acid changes was conducted to probe the structural basis for these findings. The results of this study may explain the observed absence of clinical resistance to the long-term antiviral treatment in the patients.
Identifiants
pubmed: 31585653
pii: S0378-1135(19)30825-9
doi: 10.1016/j.vetmic.2019.108398
pmc: PMC6779346
mid: NIHMS1538614
pii:
doi:
Substances chimiques
Protease Inhibitors
0
Pyrrolidines
0
RNA, Viral
0
Sulfonic Acids
0
Viral Proteins
0
GC376
H1NMJ5XDG5
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
108398Subventions
Organisme : NIAID NIH HHS
ID : R01 AI130092
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.
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