Caracterização in silico de proteínas do vírus da Zika e análise computacional de moléculas com potencial inibitório

Abstract

The Zika virus belongs to the family Flaviviridae and in in the recent years, its association with cases of microcephaly in newborns has been highlighting in the world becoming a global priority for public health. Brazil is one of the Latin American countries most affected by outbreaks caused by the Zika virus. The brisk spread and the drastic neuro-developmental problems caused by the virus in human cells, and the lack of effective treatments have led to the need to develop effective and safe antivirals in a short time period. Therefore, bioinformatics can be used as a tool to solve these problems quickly and effectively. The goal of this work was to obtain molecules with pharmacological potential to inhibit the replication of the Zika virus through the use of the non-structural proteins NS1 and NS3 of Zika Virus as a target. First, the viral proteins binding sites were identified through the metaPocket and FTMap programs and the best pockets were chosen as targets for the docking. The molecular docking was performed with AutoDock Vina and the interactions between the proteins binding sites with the ligands Niclosamide and PHA-690509 were investigated. In order to evaluate the potential of these molecules as possible competitive inhibitors, the protein-ligand complexes with lower energy, which resulted from the dockings, were analyzed and compared. Niclosamide was considered a potential inhibitor to be further explored in the treatment of Zika because of its safe use during pregnancy according to WHO and in view of the fact that the stable linkages established with the binding site of targets proteins.