Project description
Studying viral entry and immune evasion
Viral infections like dengue, Zika and Lassa fever remain difficult to treat due to the complex dynamics of viral entry and immune evasion. Complex challenges lie in understanding two key processes that can be exploited for antiviral strategy development: virion glycosylation during viral maturation and its role in immune evasion, as well as the dynamic process of viral entry into cells. The EU-funded SHIELD project addresses these challenges by combining molecular simulations, structural biology and nano-resolution microscopy to define and understand viral glycosylation and protein dynamics. SHIELD aims to leverage this knowledge to develop novel chemical and biological compounds targeting these mechanisms, with the ultimate goal of creating more effective vaccines and antiviral drugs preparing the EU for future pandemics.
Objective
The SHIELD consortium targets two closely related steps in the viral replication cycle that are, as yet, difficult to study and to exploit for therapeutic interventions: 1) Virion glycosylation in the context of uptake, maturation and viral immunity. 2) Virion dynamics of entry into cells, where the plasticity of the involved proteins and their glycosylation status have key roles. The viruses studied in SHIELD are from the genera of flavivirus (DENV, WNV, YFV, Zika), mammarenaviruses (LASV) and henipaviruses (Hendra, Nipah). We bring a broad spectrum of methodical expertise to understand and exploit the interrelated processes of viral glycosylation and viral dynamics. Molecular simulations will enable the identification of cryptic pockets in viral proteins that form during the entry process, and the design of inhibitory ligands that bind to such pockets. Theoretical methods will be used to identify ligands for glycosylated viral proteins. This is intertwined with cryo-EM and nano-resolution optical microscopy which enable a detailed analysis of these events, their sensitivity to biological and chemical interference, and will allow a rational optimization of specificity and affinity. Novel chemical and biological entities (NCEs, NBEs) as tool compounds and potential starting points for drug development are obtained by targeted chemical synthesis, X-ray fragment screening, and nanobody library screens. Additionally, we study biological processes and the influence of interactions in systems of increasing complexity, which range from biochemical in-vitro to cellular assays and in vivo animal models. As the ‘glycan shield’ in Lassa/Hendra/Nipah plays a major role in immune evasion, we explore the immunological effects of an interference with protein glycosylation leading to novel starting point towards the development of effective and robust vaccines. In conclusion, SHIELD delivers a deeper understanding, and molecular tools to prepare the EU for future pandemic events.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
This project's classification has been validated by the project's team.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
This project's classification has been validated by the project's team.
- natural sciences biological sciences microbiology virology
- medical and health sciences basic medicine medicinal chemistry
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs vaccines
- natural sciences biological sciences molecular biology structural biology
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs antivirals
Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.2.1 - Health
MAIN PROGRAMME
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HORIZON.2.1.5 - Tools, Technologies and Digital Solutions for Health and Care, including personalised medicine
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HORIZON.2.1.4 - Infectious Diseases, including poverty-related and neglected diseases
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-RIA - HORIZON Research and Innovation Actions
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-HLTH-2024-DISEASE-08
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
69117 Heidelberg
Germany
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.