SHIELD

Project Overview

Viral infections such as dengue, Zika, and Lassa fever remain difficult to treat due to the complex mechanisms viruses use to enter host cells and evade immune responses. The SHIELD project ("Molecular Strategies against Viral Entry and Glycan Shielding") focuses on two critical and closely connected stages in the viral replication cycle that remain underexplored yet offer high potential for therapeutic intervention: virion glycosylation during viral maturation, and the dynamic processes involved in viral entry into host cells.

Scientific Approach

SHIELD brings together a multidisciplinary consortium of experts to investigate how glycosylation and protein plasticity contribute to viral infectivity and immune evasion. Using advanced molecular simulations, the project aims to identify hidden or "cryptic" binding pockets that form in viral proteins during entry into cells. These insights will guide the design of inhibitory compounds that can target such transient structures. In parallel, theoretical methods are employed to predict ligands capable of binding to glycosylated viral surfaces.

These computational approaches are tightly integrated with state-of-the-art structural biology techniques, including cryo-electron microscopy and nano-resolution optical microscopy, to visualize viral components and their interactions in unprecedented detail. This allows the consortium to analyze how these processes respond to chemical or biological interference and to optimize the specificity and efficacy of potential therapeutic candidates.

Tool and Drug Development

The project aims to generate novel chemical and biological entities—small molecules, fragments, and nanobodies—that serve both as research tools and as starting points for drug development. These are identified through targeted chemical synthesis, X-ray fragment screening, and nanobody library screens. SHIELD tests these compounds in progressively complex systems, from biochemical in-vitro assays to cellular models and in vivo animal studies, ensuring translational relevance and therapeutic potential.

Towards Vaccine Innovation

In viruses such as Lassa, Hendra, and Nipah, the so-called "glycan shield" plays a key role in escaping immune detection. SHIELD explores how interfering with this glycosylation can alter immune recognition, paving the way for more effective and durable vaccine strategies.

Impact and Preparedness

Funded under Horizon Europe, SHIELD contributes to pandemic preparedness by advancing our understanding of viral entry and immune evasion and by developing molecular tools to counteract these mechanisms. The project aims to deliver not only scientific insights but also practical outcomes that support the development of next-generation antiviral therapies and vaccines—helping to safeguard Europe against future infectious disease threats.