(Invited) Sugar/Nanocarbon Hybrids As Multivalent Inhibitors of Artificial Ebola Virus Infection
Authors: Martin Nazario , Illescas Beatriz , Muñoz Antonio 
Published: February 2020

In the burgeoning area of nanoscience, scientists are currently focusing their attention on carbon nanomaterials for biomedical applications. The chemical modification of these nanomaterials is allowing to increase their biocompatibility and to provide new biological properties.

At the molecular level, there are a wide variety of examples where multivalency drastically enhances the interactions between biomolecules in comparison with the monovalent binding. In particular, multivalency plays a key role in the protein-glycan recognition events which usually take place in the initial steps of pathogenic infection and also at some stages of the immune response. The search for high-affinity ligands for the study and understanding of the mechanisms involved in multivalent interactions has yielded a wide variety of artificial glycoconjugates which include, among others, glycopolymers, glycodendrimers, and glyconanoparticles. SWCNTs and SWCNHs constitute a less-explored type of unconventional and biocompatible scaffolds for the preparation of new glycoconjugates for a multivalent presentation of carbohydrates.

Recently, we have shown that fullerene sugar balls, namely hexakis-adducts of [60]fullerene appended with 12, 24 or 36 mannose moieties, act as strong inhibitors for DC-SIGN in an Ebola infection assay model.1 Furthermore, a drastic increase in the inhibition process to the subnanomolar scale has been observed when the size and mannoses´ number are increased in the tridecafullerenes endowed with 120 mannose units decorating the periphery of the molecule.2

In this work, we report how SWCNTs and SWCNHs have been employed as virus mimicking nanocarbons platforms for the multivalent presentation of carbohydrates in an artificial Ebola virus infection model. These carbon nanoforms have been chemically modified by the covalent attachment of glycofullerenes using the CuAAC “click chemistry” approach. This modification dramatically increases the water solubility of these structurally different nanocarbons. Their efficiency to block DC-SIGN mediated viral infection by an artificial Ebola virus has been tested in a cellular experimental assay finding that, in contrast to SWCNTs, glycoconjugates based on 3D Dahlia Flower shaped SWCNHs are potent inhibitors of viral infection.

References

1. a) J. Luczkowiak, A. Muñoz, M. Sánchez-Navarro, R. Ribeiro-Viana, A. Ginieis, B. M. Illescas, N. Martín, R. Delgado, J. Rojo, Biomacromolecules
2013, 14, 431-437; b) J.-F. Nierengarten, J. Iehl, V. Oerthel, M. Holler, B. M. Illescas, A. Muñoz, N. Martín, J. Rojo, M. Sánchez-Navarro, S. Cecioni, S. Vidal, K. Buffet, M. Durka, S. P. Vincent, Chem. Commun.
2010, 46, 3860-3862; c) M. Sánchez-Navarro, A. Muñoz, B. M. Illescas, J. Rojo, N. Martín, Chem. Eur. J.
2011, 17, 766-769.

2. A. Muñoz, D. Sigwalt, B. M. Illescas, J. Luczkowiak, L. Rodríguez, I. Nierengarten, M. Holler, J.-S. Remy, K. Buffet, S. P. Vincent, J. Rojo, R. Delgado, J.-F. Nierengarten, N. Martín, Nat. Chem., 2015, DOI: 10.1038/nchem.2387.

Figure 1