title: Antiviral activity of lanatoside C against dengue virus infection.
abstract: Dengue infection poses a serious threat globally due to its recent rapid spread and rise in incidence. Currently, there is no approved vaccine or effective antiviral drug for dengue virus infection. In response to the urgent need for the development of an effective antiviral for dengue virus, the US Drug Collection library was screened in this study to identify compounds with anti-dengue activities. Lanatoside C, an FDA approved cardiac glycoside was identified as a candidate anti-dengue compound. Our data revealed that lanatoside C has an IC50 of 0.19μM for dengue virus infection in HuH-7 cells. Dose-dependent reduction in dengue viral RNA and viral proteins synthesis were also observed upon treatment with increasing concentrations of lanatoside C. Time of addition study indicated that lanatoside C inhibits the early processes of the dengue virus replication cycle. Furthermore, lanatoside C can effectively inhibit all four serotypes of dengue virus, flavivirus Kunjin, alphavirus Chikungunya and Sindbis virus as well as the human enterovirus 71. These findings suggest that lanatoside C possesses broad spectrum antiviral activity against several groups of positive-sense RNA viruses.
authors.affiliation: Laboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System, 5 Science Drive 2, National University of Singapore, Singapore 117597, Singapore.
authors.forename: Yan Yi
authors.initials: YY
authors.lastname: Cheung
authors.affiliation: Laboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System, 5 Science Drive 2, National University of Singapore, Singapore 117597, Singapore.
authors.forename: Karen Caiyun
authors.initials: KC
authors.lastname: Chen
authors.affiliation: Laboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System, 5 Science Drive 2, National University of Singapore, Singapore 117597, Singapore.
authors.forename: Huixin
authors.initials: H
authors.lastname: Chen
authors.affiliation: School of Chemical & Life Sciences, 180 Ang Mo Kio Ave 8, Nanyang Polytechnic, Singapore 569830, Singapore.
authors.forename: Eng Khuan
authors.initials: EK
authors.lastname: Seng
authors.affiliation: Laboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System, 5 Science Drive 2, National University of Singapore, Singapore 117597, Singapore. Electronic address: miccjh@nus.edu.sg.
authors.forename: Justin Jang Hann
authors.initials: JJ
authors.lastname: Chu
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D003715:Dengue / Q000188:drug therapy / Q000821:virology*; D003716:Dengue Virus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007799:Lanatosides / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D007799:Lanatosides; C018548:lanatoside C
keywords: Antiviral compounds; Cardiac glycoside; Dengue virus; Flavivirus; Lanatoside C