Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/35506
Title: The Adenosine Analogue NITD008 has Potent Antiviral Activity against Human and Animal Caliciviruses
Authors: Tuipulotu, Daniel Enosi
Fumian, Tulio M.
Netzler, Natalie E.
Mackenzie, Jason M.
White, Peter A.
Affilliation: University of New South Wales. School of Biotechnology and Biomolecular Sciences. Sydney, Australia.
University of New South Wales. School of Biotechnology and Biomolecular Sciences. Sydney, Australia / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Virologia Comparada e Ambiental. Rio de Janeiro, RJ, Brasil.
University of New South Wales. School of Biotechnology and Biomolecular Sciences. Sydney, Australia.
University of Melbourne. Peter Doherty Institute for Infection and Immunity. Department of Microbiology and Immunology. Melbourne, Australia.
University of New South Wales. School of Biotechnology and Biomolecular Sciences. Sydney, Australia.
Abstract: 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 in vitro 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 EC50 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'-C-methylcytidine in vitro. 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 in vivo. 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.
Keywords: Norovirus
Antivirals
Polymerase inhibitor
Nucleoside analogue
Caliciviruses
keywords: Norovirus
Caliciviridae
Antivirais
Nucleosídeos
Inibidor da polimerase
DeCS: Nucleosídeos
Issue Date: 2019
Publisher: MDPI
Citation: TUIPULOTU, Daniel Elosi et al. The Adenosine Analogue NITD008 has Potent Antiviral Activity against Human and Animal Caliciviruses. Viruses, v. 11, n. 496, p. 1-12, May 2019.
DOI: 10.3390/v11060496
ISSN: 1999-4915
Copyright: open access
Appears in Collections:IOC - Artigos de Periódicos

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