Potential Therapeutic Agents for Feline Calicivirus Infection
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 antivira...
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MDPI AG
2018-08-01
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| Online Access: | http://www.mdpi.com/1999-4915/10/8/433 |
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| author | Tulio M. Fumian Daniel Enosi Tuipulotu Natalie E. Netzler Jennifer H. Lun Alice G. Russo Grace J. H. Yan Peter A. White |
| author_facet | Tulio M. Fumian Daniel Enosi Tuipulotu Natalie E. Netzler Jennifer H. Lun Alice G. Russo Grace J. H. Yan Peter A. White |
| author_sort | Tulio M. Fumian |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T08:30:09Z |
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| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-12-11T08:30:09Z |
| publishDate | 2018-08-01 |
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| record_format | Article |
| series | Viruses |
| spelling | doaj.art-a90c2cf76f714d16ad9de9b76e6e527a2022-12-22T01:14:28ZengMDPI AGViruses1999-49152018-08-0110843310.3390/v10080433v10080433Potential Therapeutic Agents for Feline Calicivirus InfectionTulio M. Fumian0Daniel Enosi Tuipulotu1Natalie E. Netzler2Jennifer H. Lun3Alice G. Russo4Grace J. H. Yan5Peter A. White6School of Biotechnology and Biomolecular Sciences, Faculty of Science, University of New South Wales, Sydney, NSW 2052, AustraliaSchool of Biotechnology and Biomolecular Sciences, Faculty of Science, University of New South Wales, Sydney, NSW 2052, AustraliaSchool of Biotechnology and Biomolecular Sciences, Faculty of Science, University of New South Wales, Sydney, NSW 2052, AustraliaSchool of Biotechnology and Biomolecular Sciences, Faculty of Science, University of New South Wales, Sydney, NSW 2052, AustraliaSchool of Biotechnology and Biomolecular Sciences, Faculty of Science, University of New South Wales, Sydney, NSW 2052, AustraliaSchool of Biotechnology and Biomolecular Sciences, Faculty of Science, University of New South Wales, Sydney, NSW 2052, AustraliaSchool of Biotechnology and Biomolecular Sciences, Faculty of Science, University of New South Wales, Sydney, NSW 2052, AustraliaFeline 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.http://www.mdpi.com/1999-4915/10/8/433feline calicivirusantiviralsnucleoside analoguesnon-nucleoside inhibitorsprotease inhibitors |
| spellingShingle | Tulio M. Fumian Daniel Enosi Tuipulotu Natalie E. Netzler Jennifer H. Lun Alice G. Russo Grace J. H. Yan Peter A. White Potential Therapeutic Agents for Feline Calicivirus Infection Viruses feline calicivirus antivirals nucleoside analogues non-nucleoside inhibitors protease inhibitors |
| title | Potential Therapeutic Agents for Feline Calicivirus Infection |
| title_full | Potential Therapeutic Agents for Feline Calicivirus Infection |
| title_fullStr | Potential Therapeutic Agents for Feline Calicivirus Infection |
| title_full_unstemmed | Potential Therapeutic Agents for Feline Calicivirus Infection |
| title_short | Potential Therapeutic Agents for Feline Calicivirus Infection |
| title_sort | potential therapeutic agents for feline calicivirus infection |
| topic | feline calicivirus antivirals nucleoside analogues non-nucleoside inhibitors protease inhibitors |
| url | http://www.mdpi.com/1999-4915/10/8/433 |
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