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

作者：Quintana Veronica M; Piccini Luana E; Panozzo Zenere Juan D; Damonte Elsa B; Ponce Maria A; Castilla Viviana

来源：Antiviral Research, 2016, 134: 26-33.

DOI：10.1016/j.antiviral.2016.08.018

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 beta-carbolines against DENV-2 multiplication in cell cultures. We determined that the natural beta-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.

• 出版日期2016-10