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

• Published in: Antiviral research 2015-04, Vol.116, p.1-9
• Main Authors: Lee, Jin-Ching, Tseng, Chin-Kai, Wu, Yu-Hsuan, Kaushik-Basu, Neerja, Lin, Chun-Kuang, Chen, Wei-Chun, Wu, Huey-Nan
• Format: Article
• Language: English
• Subjects: 2′-C-methylcytidine; Animals; Antiviral Agents - pharmacology; Biological Assay; Cercopithecus aethiops; Cytidine - analogs & derivatives; Cytidine - pharmacology; Dengue - drug therapy; Dengue - virology; Dengue virus; Dengue Virus - drug effects; Dengue Virus - growth & development; Disease Models, Animal; Mice; Replicon - drug effects; RNA polymerase; RNA, Viral - genetics; Transplantation, Heterologous; Vero Cells; Virus Replication - drug effects
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2015.01.002

•2′-C-methylcytidine (2CMC) inhibits dengue virus RNA polymerase activity.•2CMC inhibits DENV infection in DENV-infected ICR suckling mice in vivo.•2CMC inhibits DENV replication in xenograft bioluminescence-based DENV replicon mice. 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.