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Identification of a small-molecule inhibitor of dengue virus using a replicon system

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Abstract

Dengue virus (DENV) is a mosquito-borne human pathogen that causes a serious public-health threat in tropical and subtropical regions of the world. Neither a vaccine to prevent nor an effective therapeutic agent to treat DENV infection is currently available. We established a stable cell line harboring a luciferase-reporting DENV subgenomic replicon to screen for inhibitors of DENV. A total of 14,400 small-molecule (MW < 500 Da) chemicals were evaluated for their ability to reduce luciferase reporter activity in cell lysates. One effective compound was identified from the screening. This compound was found to reduce virus production but did not block virus entry in virus-based assay. Mode-of-action analysis revealed that this inhibitor suppressed viral RNA replication but did not affect replicon translation. This compound potentially could be developed as an anti-DENV agent and might be useful for dissecting the molecular mechanism of DENV replication.

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Acknowledgments

This work was supported by grants from Academia Sinica, Taiwan (AS-97-40-12), and National Health Research Institute, Taiwan (NHRI-EX99-9745SI). The authors thank Dr. Heiko Kuhn for manuscript editing.

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Authors and Affiliations

  1. Institute of Molecular Biology, Academia Sinica, Taipei, 11529, Taiwan

    Yu-Chen Hsu, Nai-Chi Chen, Po-Chiang Chen, Chun-Chung Wang & Huey-Nan Wu

  2. Graduate Institute of Cell and Molecular Biology, Taipei Medical University, Taipei, Taiwan

    Nai-Chi Chen

  3. Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan

    Chun-Chung Wang

  4. Genomic Research Center, Academia Sinica, Taipei, Taiwan

    Wei-Chieh Cheng

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  1. Yu-Chen Hsu
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  2. Nai-Chi Chen
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  3. Po-Chiang Chen
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  4. Chun-Chung Wang
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  5. Wei-Chieh Cheng
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Corresponding author

Correspondence to Huey-Nan Wu.

Additional information

Y.-C. Hsu and N.-C. Chen contributed equally to this work.

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Hsu, YC., Chen, NC., Chen, PC. et al. Identification of a small-molecule inhibitor of dengue virus using a replicon system. Arch Virol 157, 681–688 (2012). https://doi.org/10.1007/s00705-012-1224-z

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  • DOI: https://doi.org/10.1007/s00705-012-1224-z

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