Please use this identifier to cite or link to this item: https://doi.org/10.3851/IMP1884
Title: Narasin, a novel antiviral compound that blocks dengue virus protein expression
Authors: Low, JSY
Wu, KX
Chen, K
Ng, MML 
Chu, JJH 
Keywords: Aedes
Animals
Antiviral Agents
Blotting, Western
Cell Line
Cell Survival
Cricetinae
Dengue Virus
Dose-Response Relationship, Drug
High-Throughput Screening Assays
Humans
Inhibitory Concentration 50
Ionophores
Protein Biosynthesis
Pyrans
Reverse Transcriptase Polymerase Chain Reaction
Severe Dengue
Severity of Illness Index
Small Molecule Libraries
Tumor Cells, Cultured
Viral Proteins
Virus Replication
Issue Date: 19-Dec-2011
Publisher: International Medical Press
Citation: Low, JSY, Wu, KX, Chen, K, Ng, MML, Chu, JJH (2011-12-19). Narasin, a novel antiviral compound that blocks dengue virus protein expression. Antiviral Therapy 16 (8) : 1203-1218. ScholarBank@NUS Repository. https://doi.org/10.3851/IMP1884
Abstract: Background: Dengue virus (DENV) is a mosquito-borne virus that causes a spectrum of human diseases ranging from mild dengue fever to dengue haemorrhagic fever and dengue shock syndrome in severe cases. Currently, there is no effective antiviral therapy or vaccine against DENV infection. Methods: In order to identify potential antiviral agents against DENV, we performed high-throughput cell-based screening on a highly purified natural products library. Among the screening hits, selected compounds which displayed 50-75% inhibition against DENV2 were validated using secondary assays. Time-of-addition studies, dose-dependent assays, real time quantitative reverse transcriptase (RT)-PCR, Western blot and ultrastructural imaging were conducted in an attempt to elucidate the potential antiviral mechanisms of narasin. Results: In this study, an ionophore, narasin was selected for detailed analysis due to its strong inhibitory profile against DENV infection with minimal cytotoxicity (50% cytotoxic concentration >1,000 μM). A dose-dependent study revealed narasin to have an 50% inhibitory concentration of less than 1 μM against all four serotypes of DENV. Time-of-addition studies of narasin-treated, DENV2-infected Huh-7 cells suggested narasin to be involved in inhibiting the post-entry stages of viral replication during DENV infection. Proteomic and ultrastructural analyses revealed the antiviral mechanism of narasin as likely to be associated with the disruption of viral protein synthesis. In addition, quantitative RT-PCR studies showed no differences in viral RNA levels between narasin-treated and control DENV2-infected cells. Conclusions: Narasin was identified and characterized as a novel agent that inhibits DENV replication in vitro through non-cytotoxic mechanisms, thus indicating its potential to be further developed as a therapeutic anti-DENV agent. ©2011 International Medical Press.
Source Title: Antiviral Therapy
URI: https://scholarbank.nus.edu.sg/handle/10635/173262
ISSN: 13596535
20402058
DOI: 10.3851/IMP1884
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