Synthesis of giant globular multivalent glycofullerenes as potent inhibitors in a model of Ebola virus infection

Antonio Muñoz, David Sigwalt, Beatriz M. Illescas, Joanna Luczkowiak, Laura Rodríguez-Pérez, Iwona Nierengarten, Michel Holler, Jean Serge Remy, Kévin Buffet, Stéphane Vincent, Javier Rojo, Rafael Delgado, Jean François Nierengarten, Nazario Martín

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Abstract

The use of multivalent carbohydrate compounds to block cell-surface lectin receptors is a promising strategy to inhibit the entry of pathogens into cells and could lead to the discovery of novel antiviral agents. One of the main problems with this approach, however, is that it is difficult to make compounds of an adequate size and multivalency to mimic natural systems such as viruses. Hexakis adducts of [60]fullerene are useful building blocks in this regard because they maintain a globular shape at the same time as allowing control over the size and multivalency. Here we report water-soluble tridecafullerenes decorated with 120 peripheral carbohydrate subunits, so-called 'superballs', that can be synthesized efficiently from hexakis adducts of [60]fullerene in one step by using copper-catalysed azide-alkyne cycloaddition click chemistry. Infection assays show that these superballs are potent inhibitors of cell infection by an artificial Ebola virus with half-maximum inhibitory concentrations in the subnanomolar range.

Original languageEnglish
Pages (from-to)50-57
Number of pages8
JournalNature Chemistry
Volume8
Issue number1
DOIs
Publication statusPublished - 1 Jan 2016

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Muñoz, A., Sigwalt, D., Illescas, B. M., Luczkowiak, J., Rodríguez-Pérez, L., Nierengarten, I., Holler, M., Remy, J. S., Buffet, K., Vincent, S., Rojo, J., Delgado, R., Nierengarten, J. F., & Martín, N. (2016). Synthesis of giant globular multivalent glycofullerenes as potent inhibitors in a model of Ebola virus infection. Nature Chemistry, 8(1), 50-57. https://doi.org/10.1038/nchem.2387