STUDY OF THE INTERACTION OF PHENYLFLUORONE WITH AMINO ACIDS FROM THE GLYCOPROTEIN AND
THE ZIKA VIRUS ENVELOPE AND THEIR EFFECTS ON IN VITRO CELLS
Glioblastoma cells, Zika virus, Phenylfluorone
Zika is a virus that belongs to the Flavivirus genus, a member of the Flaviviridae family. The disease originated by this virus (that has the same name of the pathogen) has become a worldwide public health problem due to its association with microcephaly in human fetuses. In 2015, Brazil became the epicenter of the Zika outbreak, with high potential for geographic expansion to other countries. Flaviruses had high preserved amino acid residues in glycoprotein E that may be potentially covalently modified by catechols and their derivatives. OBJECTIVE: This work investigated for the first time amino acid modifications of the glycoprotein E from Zika virus envelope by a catechol derivative, Phenylfluorone, in order to evaluate its effects on the interaction with a human glioblastoma cell line. METHODOLOGY: The binding sites of phenylfluorone with amino acid residues of glycoprotein E in silico were analyzed. The non-toxic concentration of Phenylfluorone in U251 glioblastoma lineage was identified by a cell viability test. We compared the infectivity of the wild virus (not modified with Phenylfluorone) in parallel to the modified virus in Vero cell culture by viral titration. We investigated the immunological response by ELISA through the expression of cytokines TNF, IFN, IL-8 and IL-10. RESULTS: The results demonstrated that Phenylfluorone interacts more stably with the ectodomain I of glycoprotein E. U-251 glioblastoma cells are resistant to Phenylfluorone at concentrations lesser than 49,9 µM. The virus modified with Phenylfluorone at a concentration of 499 µM showed a viral titer reduction in Vero cells. There was no change in expression and interleukins in cells infected with the modified virus.