Avaliação do potencial antiviral de compostos derivados do adamantano para dengue virus

Abstract

Viruses are among the leading causes of illness around the world, including Dengue virus (DENV), which infects approximately 390 million people every year, of which 96 million develop apparent symptoms and it is estimated that 40% of the world population are living in areas at risk of contracting Dengue. Its dispersion has increased over the last few years, and the virus is now present in 128 countries. In Brazil serious epidemics have occurred in recent years, causing a great economic impact to the country and important outcomes in the affected individuals. Currently there is no specific and effective treatment for infections caused by Dengue virus, and medical care is essential for a better outcome of the infection. The search for specific antivirals is strategic. Due to their unique pharmacological properties, adamantane derivatives demonstrate proven antiviral activity for Influenza A, Human immunodeficiency virus 1 and Hepatitis C virus. Therefore, the aim of the present study is to determine in vitro the effectiveness of three new compounds (ADA1, ADA2 and ADA5) derived from Amantadine, which consists of a functional group of NH2 on carbon 5 of adamantane, against Dengue virus 4 (DENV-4). The assays performed with MTT and AlamarBlue techniques demonstrated that the three compounds did not show cytotoxicity in BHK-21 cells at concentrations of 200 μM (with the exception of ADA5) up to 0.0002 μM. The antiviral activity assay carried out by titration in BHK-21 cells (plaque reduction assay), demonstrated that the compounds ADA1 and ADA2, at a concentration of 200μM, reduced by 4 (100%) and 2 log (50%), respectively, the titers of DENV-4. A reduction of about 1 log (25%) in the viral titer of DENV-4 was also observed for the three compounds at concentrations of 20 μM and 2 μM. In conclusion, the compounds ADA1 and ADA2 at a concentration of 200 μM present antiviral potential for DENV-4 and according to preliminary results this potential extends to the other serotypes DENV-1, 2 and 3.