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

PICCINI, L.E.; PONCE, M.A.; PANOZZO ZENERE J,D.; CASTILLA, V.; QUINTANA, V.M.; DAMONTE, E.B.

ANTIVIRAL RESEARCH

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2016 vol. 134 p. 26 - 33

0166-3542

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 b-carbolines against DENV-2 multiplicationin cell cultures. We determined that the natural b-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 mediumaffecting 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.