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CARMUSYS — Result In Brief

Project ID: 213592
Funded under: FP7-PEOPLE

Glycosciences network

A large multidisciplinary consortium investigated the complex immune mechanisms involving dendritic cell-specific receptors (DC-SIGN)–mediated pathogen recognition. The generated systems mimicked pathogen carbohydrates, resembled the structure of natural viruses and, interestingly, demonstrated antiviral activity.
Glycosciences network
Immune system responses against pathogens are triggered by immune cell receptors recognising the pathogen’s carbohydrate epitopes. Dissecting the carbohydrate–receptor interactions could enable the design of innovative anti-microbial agents.

Seeking to address this, the training network of the EU-funded CARMUSYS project brought together 12 groups from 7 European countries. The key objective was to provide training for early-stage researchers in the form of PhD fellowships in the field of carbohydrate science. Information about the partners and activities is available on the project website.

The scientific activities of the project focused on the design and synthesis of carbohydrate multivalent systems. These would be used as tools to study the interaction between carbohydrates and DC-SIGN involved in pathogen recognition. The long-term goal was to design molecules that could interfere with pathogen attachment and entry into cells.

DC-SIGN putative ligands were analysed in silico, synthesised and then presented on multivalent scaffolds prior to being biologically evaluated. The generated glycomimetic ligands were assessed for their ability to block pathogen infection.

The selectivity of the CARMUSYS approach was demonstrated for the DC-SIGN versus langerin molecules, that both mediate HIV entry. Furthermore, nanoparticles displaying thousands of glycan ligands on their surface blocked infection from the Ebola virus even at extremely low concentrations.

Taken together, the findings of the CARMUSYS network validated the anti-microbial approach through modulation of DC-SIGN activity. The advantage of the current approach is that the size and multivalency of the nanoparticles can be designed to resemble natural viruses.

In vitro testing has demonstrated that these carbohydrate ligand systems interfere with pathogen pattern-recognition receptors and compete with pathogens during their entry into target cells. Positive in vivo testing and clinical trial results will have major implications for biomedicine with increasing applications and research in carbohydrate sciences.

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