Construção de modelo e triagem virtual baseada em forma de potenciais inibidores da protease NS2B-NS3 do vírus da dengue

Abstract

Dengue virus is a member of the Flavivirus genus of the Flaviviridae family and includes four different serotypes (DENV 1 to 4). Estimates suggest that half of the population lives in areas at risk of infection. Therefore, there is an urgent need to identify and develop effective antiviral drugs for this virus. A widely used approach is the search for compounds capable of inhibiting viral replication. The NS2B-NS3 protein plays an important role in virus replication, being responsible for the cleavage of viral polyproteins and consequent maturation of the viral particle, being an interesting target for drug development. Thus, this work proposes the construction of a model for virtual screening of potential inhibitors of the NS2B-NS3 protease of the dengue virus, in addition to using the Nubbe (natural products) and ZINC (FDA - drugs approved by the US Food and Drug Administration) databases, molecular anchoring analysis and pharmacokinetic toxicity study of the best molecules found. In the screening, the VROCS program generated a ranking with the 500 best compounds that were submitted to molecular anchorage by GOLD. From the anchoring, it was possible to select two molecules from each bank with the best anchoring score and these were subjected to pharmacokinetic toxicity analysis. and the compounds of 2166 and 680, despite presenting good results in anchoring, need further studies in relation to their biological activity.