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Antiviral Res. 2015 Apr;116:1-9. doi: 10.1016/j.antiviral.2015.01.002. Epub 2015 Jan 19.

Characterization of the activity of 2'-C-methylcytidine against dengue virus replication.

Author information

1
Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan; Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: jclee@kmu.edu.tw.
2
Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
3
Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan.
4
Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, NJ, USA.
5
Doctoral Degree Program in Marine Biotechnology, National Sun Yat-Sen University, Kaohsiung, Taiwan.
6
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
7
Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan. Electronic address: hnwu@gate.sinica.edu.tw.

Abstract

Dengue virus (DENV) is a severe mosquito-borne viral pathogen. Neither vaccines nor antiviral therapy is currently available to treat DENV infection. Nucleoside inhibitors targeting viral polymerase have proved promising for the development of drugs against viruses. In this study, we report a nucleoside analog, 2'-C-methylcytidine (2CMC), which exerts potent anti-DENV activity in DENV subgenomic RNA replicon and infectious systems, with an IC50 value of 11.2±0.3μM. This study utilized both cell-based and cell-free reporter assay systems to reveal the specific anti-DENV RNA polymerase activity of 2CMC. In addition, both xenograft bioluminescence-based DENV replicon and DENV-infected Institute of Cancer Research (ICR) suckling mice models evaluated the anti-DENV replication activity of 2CMC in vivo. Collectively, these findings provide a promising compound for the development of direct-acting antivirals against DENV infection.

KEYWORDS:

2′-C-methylcytidine; Dengue virus; RNA polymerase

PMID:
25614455
DOI:
10.1016/j.antiviral.2015.01.002
[Indexed for MEDLINE]

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