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High-throughput Antiviral Assays to Screen for Inhibitors of Zika Virus Replication
Published on: October 30, 2021
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Tizoxanide Antiviral Activity on Dengue Virus Replication
Kristie A Yamamoto1, Kevin Blackburn2, Michael B Goshe2
1Department of Biochemistry, Institute of Chemistry, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-909, Brazil.
Viruses
|March 30, 2023
Summary
Tizoxanide (TIZ) shows promise as an antiviral treatment, inhibiting dengue virus type 2 (DENV-2) replication within cells. This drug interferes with viral processes and may activate immune responses, reducing DENV-2 production.
Area of Science:
- Virology
- Drug Discovery
- Molecular Biology
Background:
- Dengue virus (DENV) poses a significant public health threat in Brazil, causing widespread illness and mortality.
- Existing treatments for dengue are limited, highlighting the need for novel therapeutic strategies.
Purpose of the Study:
- To evaluate the antiviral activity, biological activity, and toxicity of tizoxanide (TIZ) against dengue virus type 2 (DENV-2).
- To investigate the mechanism of action of TIZ in infected cells.
Main Methods:
- Vero cell cultures were infected with DENV-2 and subsequently treated with varying concentrations of TIZ.
- Viral production was quantified to assess antiviral efficacy.
- Label-free quantitative proteomics was employed to analyze protein expression profiles in treated and untreated cells.
Main Results:
- TIZ demonstrated significant antiviral activity by inhibiting DENV-2 replication intracellularly, post-penetration and pre-genome replication.
- Proteomic analysis revealed that TIZ interferes with cellular processes including intracellular trafficking, vesicle-mediated transport, and post-translational modifications.
- TIZ treatment led to the activation of immune response genes, contributing to reduced DENV-2 production.
Conclusions:
- Tizoxanide is a potent inhibitor of DENV-2 replication in cell culture.
- TIZ exhibits a promising therapeutic potential for managing DENV-2 infections by modulating host cell processes and immune responses.
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