Potential Therapeutic Agents for Feline Calicivirus Infection.

Fumian, TM; Tuipulotu, DE; Netzler, NE; Lun, JH; Russo, AG; Yan, GJH; White, PA

Potential Therapeutic Agents for Feline Calicivirus Infection.

Fumian, TM Tuipulotu, DE Netzler, NE Lun, JH Russo, AG Yan, GJH White, PA

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Publisher:: MDPI
Publication Type:: Journal Article
Citation:: Viruses, 2018, 10, (8), pp. E433
Issue Date:: 2018-08-16

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Field	Value	Language
dc.contributor.author	Fumian, TM
dc.contributor.author	Tuipulotu, DE
dc.contributor.author	Netzler, NE
dc.contributor.author	Lun, JH
dc.contributor.author	Russo, AG
dc.contributor.author	Yan, GJH
dc.contributor.author	White, PA
dc.date.accessioned	2025-01-15T13:33:42Z
dc.date.available	2018-08-15
dc.date.available	2025-01-15T13:33:42Z
dc.date.issued	2018-08-16
dc.identifier.citation	Viruses, 2018, 10, (8), pp. E433
dc.identifier.issn	1999-4915
dc.identifier.issn	1999-4915
dc.identifier.uri	http://hdl.handle.net/10453/183656
dc.description.abstract	Feline calicivirus (FCV) is a major cause of upper respiratory tract disease in cats, with widespread distribution in the feline population. Recently, virulent systemic diseases caused by FCV infection has been associated with mortality rates up to 50%. Currently, there are no direct-acting antivirals approved for the treatment of FCV infection. Here, we tested 15 compounds from different antiviral classes against FCV using in vitro protein and cell culture assays. After the expression of FCV protease-polymerase protein, we established two in vitro assays to assess the inhibitory activity of compounds directly against the FCV protease or polymerase. Using this recombinant enzyme, we identified quercetagetin and PPNDS as inhibitors of FCV polymerase activity (IC50 values of 2.8 μM and 2.7 μM, respectively). We also demonstrate the inhibition of FCV protease activity by GC376 (IC50 of 18 µM). Using cell culture assays, PPNDS, quercetagetin and GC376 did not display antivirals effects, however, we identified nitazoxanide and 2'-C-methylcytidine (2CMC) as potent inhibitors of FCV replication, with EC50 values in the low micromolar range (0.6 μM and 2.5 μM, respectively). In conclusion, we established two in vitro assays that will accelerate the research for FCV antivirals and can be used for the high-throughput screening of direct-acting antivirals.
dc.format	Electronic
dc.language	eng
dc.publisher	MDPI
dc.relation.ispartof	Viruses
dc.relation.isbasedon	10.3390/v10080433
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	0605 Microbiology
dc.subject.classification	3107 Microbiology
dc.subject.mesh	Animals
dc.subject.mesh	Antiviral Agents
dc.subject.mesh	Caliciviridae Infections
dc.subject.mesh	Calicivirus, Feline
dc.subject.mesh	Cat Diseases
dc.subject.mesh	Cats
dc.subject.mesh	Cell Line
dc.subject.mesh	Cytidine
dc.subject.mesh	DNA-Directed RNA Polymerases
dc.subject.mesh	Epithelial Cells
dc.subject.mesh	Flavones
dc.subject.mesh	Gene Expression
dc.subject.mesh	High-Throughput Screening Assays
dc.subject.mesh	Inhibitory Concentration 50
dc.subject.mesh	Nitro Compounds
dc.subject.mesh	Peptide Hydrolases
dc.subject.mesh	Polyproteins
dc.subject.mesh	Pyridoxal Phosphate
dc.subject.mesh	Recombinant Proteins
dc.subject.mesh	Respiratory Tract Infections
dc.subject.mesh	Sulfonic Acids
dc.subject.mesh	Thiazoles
dc.subject.mesh	Cell Line
dc.subject.mesh	Epithelial Cells
dc.subject.mesh	Animals
dc.subject.mesh	Cats
dc.subject.mesh	Calicivirus, Feline
dc.subject.mesh	Respiratory Tract Infections
dc.subject.mesh	Caliciviridae Infections
dc.subject.mesh	Cat Diseases
dc.subject.mesh	Sulfonic Acids
dc.subject.mesh	Nitro Compounds
dc.subject.mesh	Pyridoxal Phosphate
dc.subject.mesh	Thiazoles
dc.subject.mesh	Flavones
dc.subject.mesh	Peptide Hydrolases
dc.subject.mesh	DNA-Directed RNA Polymerases
dc.subject.mesh	Polyproteins
dc.subject.mesh	Recombinant Proteins
dc.subject.mesh	Cytidine
dc.subject.mesh	Antiviral Agents
dc.subject.mesh	Inhibitory Concentration 50
dc.subject.mesh	Gene Expression
dc.subject.mesh	High-Throughput Screening Assays
dc.subject.mesh	Animals
dc.subject.mesh	Antiviral Agents
dc.subject.mesh	Caliciviridae Infections
dc.subject.mesh	Calicivirus, Feline
dc.subject.mesh	Cat Diseases
dc.subject.mesh	Cats
dc.subject.mesh	Cell Line
dc.subject.mesh	Cytidine
dc.subject.mesh	DNA-Directed RNA Polymerases
dc.subject.mesh	Epithelial Cells
dc.subject.mesh	Flavones
dc.subject.mesh	Gene Expression
dc.subject.mesh	High-Throughput Screening Assays
dc.subject.mesh	Inhibitory Concentration 50
dc.subject.mesh	Nitro Compounds
dc.subject.mesh	Peptide Hydrolases
dc.subject.mesh	Polyproteins
dc.subject.mesh	Pyridoxal Phosphate
dc.subject.mesh	Recombinant Proteins
dc.subject.mesh	Respiratory Tract Infections
dc.subject.mesh	Sulfonic Acids
dc.subject.mesh	Thiazoles
dc.title	Potential Therapeutic Agents for Feline Calicivirus Infection.
dc.type	Journal Article
utslib.citation.volume	10
utslib.location.activity	Switzerland
utslib.for	0605 Microbiology
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Science
pubs.organisational-group	University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	open_access	*
dc.rights.license	This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/
dc.date.updated	2025-01-15T13:33:38Z
pubs.issue	8
pubs.publication-status	Published online
pubs.volume	10
utslib.citation.issue	8

Abstract:

Feline calicivirus (FCV) is a major cause of upper respiratory tract disease in cats, with widespread distribution in the feline population. Recently, virulent systemic diseases caused by FCV infection has been associated with mortality rates up to 50%. Currently, there are no direct-acting antivirals approved for the treatment of FCV infection. Here, we tested 15 compounds from different antiviral classes against FCV using in vitro protein and cell culture assays. After the expression of FCV protease-polymerase protein, we established two in vitro assays to assess the inhibitory activity of compounds directly against the FCV protease or polymerase. Using this recombinant enzyme, we identified quercetagetin and PPNDS as inhibitors of FCV polymerase activity (IC50 values of 2.8 μM and 2.7 μM, respectively). We also demonstrate the inhibition of FCV protease activity by GC376 (IC50 of 18 µM). Using cell culture assays, PPNDS, quercetagetin and GC376 did not display antivirals effects, however, we identified nitazoxanide and 2'-C-methylcytidine (2CMC) as potent inhibitors of FCV replication, with EC50 values in the low micromolar range (0.6 μM and 2.5 μM, respectively). In conclusion, we established two in vitro assays that will accelerate the research for FCV antivirals and can be used for the high-throughput screening of direct-acting antivirals.

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http://hdl.handle.net/10453/183656