دانلود رایگان مقاله فعالیت ضد ویروسی بتا-کربولین طبیعی و مصنوعی ضد ویروس دانگ

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 b-carbolines against DENV-2 multiplication in 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 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.

4. Discussion

Despite the increasing risk of DENV infection in tropical and subtropical regions of the world there is no available antiviral chemotherapy to face dengue (Guzman and Harris, 2015; John et al., 2015). Even though the inhibitory effect of b-carbolines on the multiplication of several viruses has been reported, there has been no research into the potential of these compounds as antiviral agents against DENV. In the present study we evaluated the antiviral activity of 4 natural b-carbolines and 8 synthetic derivatives against DENV-2 in Vero cell cultures. We found that harmol and 9N-methylharmine inhibit DENV-2 multiplication and lack direct inactivating effect on DENV-2 particles.