title: Antiviral activity of natural and synthetic β-carbolines against dengue virus.
abstract: Dengue virus (DENV) is the most prevalent mosquito borne viral pathogen worldwide. In this work we first evaluated the antiviral activity of natural and synthetic β-carbolines against DENV-2 multiplication in cell cultures. We determined that the natural β-carboline harmol and a synthetic harmine derivative, 9N-methylharmine, exhibit inhibitory effect on DENV-2 production without virucidal activity. The active compounds were inhibitory of all DENV serotypes, being DENV-2 the more susceptible to their antiviral action. The mode of action of 9N-methylharmine against DENV-2 was further explored. We determined that the derivative neither affects viral adsorption-internalization events nor viral RNA synthesis. The quantification of intracellular and extracellular viral genomes and infectious virus particles indicated that 9N-methylharmine would impair the maturation and release of virus particles to the extracellular medium affecting the spreading of the infection. Furthermore, we also determined that 9N-methylharmine antiviral activity is not related to the ability of the compound to downregulate p38 MAPK phosphorylation.
authors: Laboratorio de Virología, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (UBA), Ciudad Universitaria, Pabellón 2, Piso 4, Ciudad Autónoma de Buenos Aires, C1428EGA, Argentina.
authors: Verónica M
authors: VM
authors: Quintana
authors: Laboratorio de Virología, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (UBA), Ciudad Universitaria, Pabellón 2, Piso 4, Ciudad Autónoma de Buenos Aires, C1428EGA, Argentina; IQUIBICEN, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET-UBA), Ciudad Universitaria, Buenos Aires, Argentina.
authors: Luana E
authors: LE
authors: Piccini
authors: Laboratorio de Virología, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (UBA), Ciudad Universitaria, Pabellón 2, Piso 4, Ciudad Autónoma de Buenos Aires, C1428EGA, Argentina.
authors: Juan D
authors: JD
authors: Panozzo Zénere
authors: Laboratorio de Virología, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (UBA), Ciudad Universitaria, Pabellón 2, Piso 4, Ciudad Autónoma de Buenos Aires, C1428EGA, Argentina; IQUIBICEN, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET-UBA), Ciudad Universitaria, Buenos Aires, Argentina.
authors: Elsa B
authors: EB
authors: Damonte
authors: Ciclo Básico Común, Universidad de Buenos Aires (UBA), Ramos Mejía 841, Buenos Aires, Argentina.
authors: María A
authors: MA
authors: Ponce
authors: Laboratorio de Virología, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (UBA), Ciudad Universitaria, Pabellón 2, Piso 4, Ciudad Autónoma de Buenos Aires, C1428EGA, Argentina. Electronic address: viviana@qb.fcen.uba.ar.
authors: Viviana
authors: V
authors: Castilla
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002243:Carbolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D003716:Dengue Virus / Q000187:drug effects* / Q000235:genetics; D055808:Drug Discovery; D016679:Genome, Viral / Q000187:drug effects; D006247:Harmine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D012367:RNA, Viral / Q000187:drug effects; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D002243:Carbolines; D012367:RNA, Viral; C001326:harmol; D006247:Harmine; C010262:norharman; D048051:p38 Mitogen-Activated Protein Kinases