Antiviral Evaluation of New Synthetic Bioconjugates Based on GA-Hecate: A New Class of Antivirals Targeting Different Steps of Zika Virus Replication.

Re-emerging arboviruses represent a serious health problem due to their rapid vector-mediated spread, mainly in urban tropical areas. The 2013-2015 Zika virus (ZIKV) outbreak in South and Central America has been associated with cases of microcephaly in newborns and Guillain-Barret syndrome. We previously showed that the conjugate gallic acid-Hecate (GA-FALALKALKKALKKLKKALKKAL-CONH2)-is an efficient inhibitor of the hepatitis C virus. Here, we show that the Hecate peptide is degraded in human blood serum into three major metabolites. These metabolites conjugated with gallic acid were synthesized and their effect on ZIKV replication in cultured cells was evaluated. The GA-metabolite 5 (GA-FALALKALKKALKKL-COOH) was the most efficient in inhibiting two ZIKV strains of African and Asian lineage at the stage of both virus entry (virucidal and protective) and replication (post-entry). We also demonstrate that GA-metabolite 5 does not affect cell growth after 7 days of continuous treatment. Thus, this study identifies a new synthetic antiviral compound targeting different steps of ZIKV replication in vitro and with the potential for broad reactivity against other flaviviruses. Our work highlights a promising strategy for the development of new antivirals based on peptide metabolism and bioconjugation.

Expression of gynoecium patterning transcription factors in Aristolochia fimbriata (Aristolochiaceae) and their contribution to gynostemium development.

BACKGROUND: In Aristolochia (Aristolochiaceae) flowers, the congenital fusion of the anthers and the commissural, stigmatic lobes forms a gynostemium. Although the molecular bases associated to the apical-basal gynoecium patterning have been described in eudicots, comparative expression studies of the style and stigma regulatory genes have never been performed in early divergent angiosperms possessing a gynostemium. RESULTS: In this study, we assess the expression of five genes typically involved in gynoecium development in Aristolochia fimbriata. We found that all five genes (AfimCRC, AfimSPT, AfimNGA, AfimHEC1 and AfimHEC3) are expressed in the ovary, the placenta, the ovules and the transmitting tract. In addition, only AfimHEC3, AfimNGA and AfimSPT are temporarily expressed during the initiation of the stigma, while none of the genes studied is maintained during the elaboration of the stigmatic surfaces in the gynostemium. CONCLUSIONS: Expression patterns suggest that CRC, HEC, NGA and SPT homologs establish ovary and style identity in Aristolochia fimbriata. Only NGA,HEC3 and SPT genes may play a role in the early differentiation of the stigmatic lobes, but none of the genes studied seems to control late stigma differentiation in the gynostemium. The data gathered so far raises the possibility that such transient expression early on provides sufficient signal for late stigma differentiation or that unidentified late identity genes are controlling stigma development in the gynostemium. Our data does not rule out the possibility that stigmas could correspond to staminal filaments with convergent pollen-receptive surfaces.