title: Characterization of the activity of 2'-C-methylcytidine against dengue virus replication.
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.
authors.affiliation: 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.
authors.forename: Jin-Ching
authors.initials: JC
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: Chin-Kai
authors.initials: CK
authors.lastname: Tseng
authors.affiliation: Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Yu-Hsuan
authors.initials: YH
authors.lastname: Wu
authors.affiliation: Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, NJ, USA.
authors.forename: Neerja
authors.initials: N
authors.lastname: Kaushik-Basu
authors.affiliation: Doctoral Degree Program in Marine Biotechnology, National Sun Yat-Sen University, Kaohsiung, Taiwan.
authors.forename: Chun-Kuang
authors.initials: CK
authors.lastname: Lin
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Wei-Chun
authors.initials: WC
authors.lastname: Chen
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan. Electronic address: hnwu@gate.sinica.edu.tw.
authors.forename: Huey-Nan
authors.initials: HN
authors.lastname: Wu
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001681:Biological Assay; D002522:Chlorocebus aethiops; D003562:Cytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003715:Dengue / Q000188:drug therapy / Q000821:virology; D003716:Dengue Virus / Q000187:drug effects* / Q000254:growth & development; D004195:Disease Models, Animal; D051379:Mice; D012367:RNA, Viral / Q000235:genetics; D012093:Replicon / Q000187:drug effects*; D014183:Transplantation, Heterologous; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D012367:RNA, Viral; C513402:2'-C-methylcytidine; D003562:Cytidine
keywords: 2′-C-methylcytidine; Dengue virus; RNA polymerase