期刊
ANTIVIRAL RESEARCH
卷 116, 期 -, 页码 1-9出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.antiviral.2015.01.002
关键词
Dengue virus; 2'-C-methylcytidine; RNA polymerase
资金
- Ministry of Science and Technology of Taiwan [NSC 101-2311-B-037-002-MY3]
- National Sun Yat-Sen University-KMU Joint Research Project [NSYSU-KMU 103-1005]
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 +/- 0.3 mu M. 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. (C) 2015 Elsevier B.V. All rights reserved.
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