After the last epidemic of Zika virus (ZIKV) in Brazil that peacked in 2016, it has been demonstrated growing evidence of the link between this teratogenic flavivirus and microcephaly cases. However, no vaccine or antiviral drug has been yet approved. ZIKV and Dengue virus (DENV) entry to the host cell takes place through several receptors including DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin), so that the blockade of this recep-tor through multivalent glycoconjugates supposes a promising biological target to inhibit the infection process. In order to get enhanced multivalency in biocompatible systems, tridecafullerenes appended with up to 360 1,2-mannobiosides have been synthesized using a strain promoted cycloaddition of azides to alkynes (SPAAC) strategy. These systems have been tested against ZIKV and DENV infection, showing an outstanding activity in the picomolar range.