€8M Horizon Europe SHIELD project: Molecular strategies against viral entry and glycan shielding

The SHIELD project is a Horizon Europe-funded initiative tackling the global threat of emerging and re-emerging viruses. With a consortium of ten leading European institutions, SHIELD targets viruses with high pandemic potential, including Flavivirus (Dengue, West Nile, Zika, Yellow Fever), Mammarenavirus (Lassa virus), and Henipavirus (Hendra, Nipah). SHIELD was awarded €8 million from the Horizon Europe call, ‘Pandemic preparedness and response: Host-pathogen interactions of infectious diseases with epidemic potential’, and will run from January 2025 for 60 months. To learn more about the project and collaboration with Catalyze, we spoke with Prof. Floris Rutjes, Director of the Institute for Molecules and Materials at Radboud University.

Project Background and Challenge

Emerging viruses pose an increasing threat due to zoonotic (animals to humans) transmission, climate change, and globalisation. The SHIELD project prioritises new therapeutic strategies to address these challenges. SHIELD will elucidate and valorise understudied mechanisms related to viral entry, such as glycosylation and virion dynamics as next generation antiviral targets.

The project consortium of 10 partners aims to deliver a methodological pipeline of novel assays, proof-of-concept target sites and molecules for further clinical development against these existing viruses, as well as bolster our ability to combat future pandemics in the EU and globally.

Reflecting on the project’s inception, Prof. Rutjes explains, “We have been working for quite some years already on antiviral small molecules. We had projects on dengue, and after the pandemic started, we also started working on projects where we were making antiviral compounds against COVID. Some of the COVID compounds are currently in preclinical development.”​

Prof. Rutjes continues, “When I saw the Horizon call offering €8 million per project I thought, this is something that we should really go for and I decided to work with Catalyze. Ultimately we ended up number two out of 41 proposals.”

“it’s a rather drastic, different approach to treating viral infection.”​

The project focuses on viral glycosylation and virion dynamics, mechanisms that are critical to immune evasion and viral entry. Glycosylation, the addition of carbohydrate modifications to proteins, creates a glycan shield that is used by viruses to mask viral proteins virus and protect it from antibody detection. There are currently no clinically approved therapeutic options targeting glycosylation, but there is promise that such an approach could be highly effective.

Prof. Rutjes describes this innovative approach: “If the building of this glycan shield is compromised because of the inhibitors, or glycoengineered host cells, or antigens that we are going to develop, the glycan shield will be disturbed. And those proteins that are being produced in the cell, they will be detected and removed by the immune system. So, it’s a rather drastic, different approach to treating viral infection.”​

Consortium and Collaborative Expertise

SHIELD’s consortium includes renowned institutions such as the University of Heidelberg (Coordinator), Radboud University, Institut Pasteur, the Bernhard-Nocht-Institute for Tropical Medicine (Germany) and Karolinska Institute (Sweden) (full consortium listed below).

Prof. Rutjes reflects on the team’s strengths: “The consortium is very good in many ways. My group is specialised in synthesising organic molecules but we also needed groups with computational modelling, glycoengineering, and structural biology expertise, antibody production, biochemical assays, cellular assays, animal facilities and many more.

“Furthermore, these are dangerous viruses so all those assays need to be run in special labs. What is additionally nice is that we have a geographic spread over Europe, a good gender balance, and representation from many different age groups. We put quite some effort into assembling a balanced team.”​

Impact and Future Potential

SHIELD’s ambition is to unlock new therapeutic and diagnostic modalities through a deeper understanding of viral glycosylation and entry processes.

Prof. Rutjes articulates the potential impact: “We hope that we find fundamentally new mechanisms to develop antiviral compounds that can be used for the viruses that we are looking at. In principal, if we show that this is a viable approach, then the impact might be much bigger than only for this programme. It could inform other antiviral strategies and be useful in vaccine development.”​

Catalyze’s Role and Continued partnership

Catalyze played an instrumental role in aligning the consortium’s ideas and ensuring the proposal met Horizon Europe’s high standards.

Prof. Rutjes acknowledges, “Writing proposals for Horizon Europe grants is so complicated that you need specialized companies to help you to have a proper chance of getting a proposal granted. Catalyze ensured that every box was ticked and took care of impact sections and other parts where we as scientists are usually not so good.

“While we had some challenges along the way, in the end their reliability and quality made a big difference. Importantly, they deliver what they promise. If I had to choose, I would continue to work with Catalyze.”

SHIELD Project Consortium

Making up the shield project is a 10 partner consortium, led by project coordinators, the University of Heidelberg.

1. University of Heidelberg (Germany)
2. Radboud Universiteit (Netherlands)
3. Bernhard-Nocht-Institute for Tropical Medicine (Germany)
4. Instituto de Tecnologia Química e Biológica António Xavier (Portugal)
5. Karolinska Institute (Sweden)
6. Institut Pasteur (France)
7. University of Copenhagen (Denmark)
8. University of Gdansk (Poland)
9. École Polytechnique Fédérale de Lausanne (Switzerland)
10. Universitätsklinikum Heidelberg (Germany)

Learn more about Horizon Europe

Radboud University Institute of Molecules and Materials