Development of new peptides and bioconjugates against Zika virus infection

Abstract

ZIKV outbreaks highlighted the fast and silent evolution of this microrganism. Miycrocephaly and another brain disorders have been associated with ZIKV infections in newborns and adults. In 2016, Mondial Health Organization (MHO) recognized the sexual transmission of ZIKV and studies have shown that viral RNA remain in men reproductive organs during over 6 months without symptomns. Despite the efforts for the development of drugs and vaccines which could help as profilactic and treatment of infections caused by ZIKV, there is no treatment approved to this disease. The compound Gallic acid - Hecate and his N-terminal metabolites have been evaluated against Vero cells and two different lineages from ZIKV (PE243 - isolated in Brazil, 2015 and MP1751 - isolated in Uganda, 1962). Using solid phase peptide synthesis, human blood serum stability assay, viability assays using WST-1 and ELISA assay targeting envelop protein E, the results have shown that serum stability methodology is an important tool to identify new compounds based on peptide structures and proteases cleavage. GA-metabolite 5 was the most efficient synthetic compound evaluated, inhibiting both strains in all entry steps and cytoplasmic replication in three high-non-toxic concentrations (40 and 20 µM). This study has shown new synthetic antiviral targeting different steps of Zika virus replication in vitro highlighting a promising strategy to development of antiviral drugs based on peptide metabolism and bioconjugation.