Inhibition of dengue virus infection by mannoside glycolipid conjugates.
Fiche publication
Date publication
avril 2018
Journal
Antiviral research
Auteurs
Membres identifiés du Cancéropôle Est :
Dr WAGNER Alain, Dr MUELLER Christopher, Dr FLACHER Vincent
Tous les auteurs :
Schaeffer E, Flacher V, Neuberg P, Hoste A, Brulefert A, Fauny JD, Wagner A, Mueller CG
Lien Pubmed
Résumé
Dengue virus (DENV), a mosquito-borne flavivirus, causes severe and potentially fatal symptoms in millions of infected individuals each year. Although dengue fever represents a major global public health problem, the vaccines or antiviral drugs proposed so far have not shown sufficient efficacy and safety, calling for new antiviral developments. Here we have shown that a mannoside glycolipid conjugate (MGC) bearing a trimannose head with a saturated lipid chain inhibited DENV productive infection. It showed remarkable cell promiscuity, being active in human skin dendritic cells, hepatoma cell lines and Vero cells, and was active against all four DENV serotypes, with an IC in the low micromolar range. Time-of-addition experiments and structure-activity analyses revealed the importance of the lipid chain to interfere with an early viral infection step. This, together with a correlation between antiviral activity and membrane polarization by the lipid moiety indicated that the inhibitor functions by blocking viral envelope fusion with the endosome membrane. These finding establish MGCs as a novel class of antivirals against the DENV.
Mots clés
Cell membrane, Dendritic cells, Dengue virus, Inhibitors, Macrophages, Skin
Référence
Antiviral Res.. 2018 Apr 6;154:116-123