2'-C-甲基胞苷抗登革病毒复制活性的表征
Characterization of the activity of 2'-C-methylcytidine against dengue virus replication.
作者信息
Lee Jin-Ching, Tseng Chin-Kai, Wu Yu-Hsuan, Kaushik-Basu Neerja, Lin Chun-Kuang, Chen Wei-Chun, Wu Huey-Nan
机构信息
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.
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.
出版信息
Antiviral Res. 2015 Apr;116:1-9. doi: 10.1016/j.antiviral.2015.01.002. Epub 2015 Jan 19.
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.
登革病毒（DENV）是一种严重的蚊媒病毒病原体。目前尚无疫苗或抗病毒疗法可用于治疗登革病毒感染。事实证明，靶向病毒聚合酶的核苷抑制剂在开发抗病毒药物方面具有前景。在本研究中，我们报告了一种核苷类似物2'-C-甲基胞苷（2CMC），它在登革病毒亚基因组RNA复制子和感染系统中发挥强大的抗登革病毒活性，IC50值为11.2±0.3μM。本研究利用基于细胞和无细胞的报告基因检测系统揭示了2CMC的特异性抗登革病毒RNA聚合酶活性。此外，基于异种移植生物发光的登革病毒复制子和登革病毒感染的癌症研究所（ICR）乳鼠模型在体内评估了2CMC的抗登革病毒复制活性。总的来说，这些发现为开发针对登革病毒感染的直接作用抗病毒药物提供了一种有前景的化合物。
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