Antiviral activity of natural and synthetic β-carbolines against dengue virus

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 de...

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Autores principales: Quintana, V.M., Piccini, L.E., Panozzo Zénere, J.D., Damonte, E.B., Ponce, M.A., Castilla, V.
Formato: JOUR
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Acceso en línea:http://hdl.handle.net/20.500.12110/paper_01663542_v134_n_p26_Quintana
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Sumario: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. © 2016 Elsevier B.V.