CHAPTER 3. Multivalent Glycosylated Carbon Nanostructures: Efficient Inhibitors of Emergent Viruses Infection

The infection of humans by lethal pathogens such as Ebola and other related viruses such as Zika and Dengue viruses has not been properly addressed so far. The entry of these viruses to the host cell takes place through several receptors including DC-SIGN, so that multivalent glycoconjugates are considered as good candidates to inhibit the viral infection process. In particular, we have focused on fullerene C60 and other carbon nanostructures as biocompatible platforms for the multivalent presentation of carbohydrates. The antiviral activity of these compounds in an Ebola pseudotyped infection model reached IC50 values in the subnanomolar range in the case of tridecafullerenes appended with 120 mannoses. SWCNTs, MWCNTs and SWCNHs have also been employed as viruses mimicking nanocarbon platforms for the multivalent presentation of carbohydrates. In particular, MWCNTs functionalized with glycofullerenes have been shown as potent inhibitors of Ebola virus infection. 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 inhibitory activity in the picomolar range.