The Adenosine Analogue NITD008 has Potent Antiviral Activity against Human and Animal Caliciviruses
The widespread nature of calicivirus infections globally has a substantial impact on the health and well-being of humans and animals alike. Currently, the only vaccines approved against caliciviruses are for feline and rabbit-specific members of this group, and thus there is a growing effort towards...
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MDPI AG
2019-05-01
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| Online Access: | https://www.mdpi.com/1999-4915/11/6/496 |
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| author | Daniel Enosi Tuipulotu Tulio M. Fumian Natalie E. Netzler Jason M. Mackenzie Peter A. White |
| author_facet | Daniel Enosi Tuipulotu Tulio M. Fumian Natalie E. Netzler Jason M. Mackenzie Peter A. White |
| author_sort | Daniel Enosi Tuipulotu |
| collection | DOAJ |
| description | The widespread nature of calicivirus infections globally has a substantial impact on the health and well-being of humans and animals alike. Currently, the only vaccines approved against caliciviruses are for feline and rabbit-specific members of this group, and thus there is a growing effort towards the development of broad-spectrum antivirals for calicivirus infections. In this study, we evaluated the antiviral activity of the adenosine analogue NITD008 <i>in vitro</i> using three calicivirus model systems namely; feline calicivirus (FCV), murine norovirus (MNV), and the human norovirus replicon. We show that the nucleoside analogue (NA), NITD008, has limited toxicity and inhibits calicivirus replication in all three model systems with EC<sub>50</sub> values of 0.94 μM, 0.91 µM, and 0.21 µM for MNV, FCV, and the Norwalk replicon, respectively. NITD008 has a similar level of potency to the most well-studied NA 2′-<i>C</i>-methylcytidine <i>in vitro</i>. Significantly, we also show that continual NITD008 treatment effectively cleared the Norwalk replicon from cells and treatment with 5 µM NITD008 was sufficient to completely prevent rebound. Given the potency displayed by NITD008 against several caliciviruses, we propose that this compound should be interrogated further to assess its effectiveness <i>in vivo</i>. In summary, we have added a potent NA to the current suite of antiviral compounds and provide a NA scaffold that could be further modified for therapeutic use against calicivirus infections. |
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| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-12-12T11:47:57Z |
| publishDate | 2019-05-01 |
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| record_format | Article |
| series | Viruses |
| spelling | doaj.art-72bfd14df60d4e4eb28551cf4b3559d22022-12-22T00:25:25ZengMDPI AGViruses1999-49152019-05-0111649610.3390/v11060496v11060496The Adenosine Analogue NITD008 has Potent Antiviral Activity against Human and Animal CalicivirusesDaniel Enosi Tuipulotu0Tulio M. Fumian1Natalie E. Netzler2Jason M. Mackenzie3Peter A. White4School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, AustraliaSchool of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, AustraliaSchool of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, AustraliaDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VC 3010, AustraliaSchool of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, AustraliaThe widespread nature of calicivirus infections globally has a substantial impact on the health and well-being of humans and animals alike. Currently, the only vaccines approved against caliciviruses are for feline and rabbit-specific members of this group, and thus there is a growing effort towards the development of broad-spectrum antivirals for calicivirus infections. In this study, we evaluated the antiviral activity of the adenosine analogue NITD008 <i>in vitro</i> using three calicivirus model systems namely; feline calicivirus (FCV), murine norovirus (MNV), and the human norovirus replicon. We show that the nucleoside analogue (NA), NITD008, has limited toxicity and inhibits calicivirus replication in all three model systems with EC<sub>50</sub> values of 0.94 μM, 0.91 µM, and 0.21 µM for MNV, FCV, and the Norwalk replicon, respectively. NITD008 has a similar level of potency to the most well-studied NA 2′-<i>C</i>-methylcytidine <i>in vitro</i>. Significantly, we also show that continual NITD008 treatment effectively cleared the Norwalk replicon from cells and treatment with 5 µM NITD008 was sufficient to completely prevent rebound. Given the potency displayed by NITD008 against several caliciviruses, we propose that this compound should be interrogated further to assess its effectiveness <i>in vivo</i>. In summary, we have added a potent NA to the current suite of antiviral compounds and provide a NA scaffold that could be further modified for therapeutic use against calicivirus infections.https://www.mdpi.com/1999-4915/11/6/496norovirusantiviralspolymerase inhibitornucleoside analoguecaliciviruses |
| spellingShingle | Daniel Enosi Tuipulotu Tulio M. Fumian Natalie E. Netzler Jason M. Mackenzie Peter A. White The Adenosine Analogue NITD008 has Potent Antiviral Activity against Human and Animal Caliciviruses Viruses norovirus antivirals polymerase inhibitor nucleoside analogue caliciviruses |
| title | The Adenosine Analogue NITD008 has Potent Antiviral Activity against Human and Animal Caliciviruses |
| title_full | The Adenosine Analogue NITD008 has Potent Antiviral Activity against Human and Animal Caliciviruses |
| title_fullStr | The Adenosine Analogue NITD008 has Potent Antiviral Activity against Human and Animal Caliciviruses |
| title_full_unstemmed | The Adenosine Analogue NITD008 has Potent Antiviral Activity against Human and Animal Caliciviruses |
| title_short | The Adenosine Analogue NITD008 has Potent Antiviral Activity against Human and Animal Caliciviruses |
| title_sort | adenosine analogue nitd008 has potent antiviral activity against human and animal caliciviruses |
| topic | norovirus antivirals polymerase inhibitor nucleoside analogue caliciviruses |
| url | https://www.mdpi.com/1999-4915/11/6/496 |
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