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Comparative signature of Marburg virus cell activation as a blueprint for the identification of antiviral targets against newly emerging viruses

Project description

Exploring the Marburg virus-cell interface for the targeted development of antivirals

Identifying cellular attachment factors and functional receptors is crucial for understanding emerging viruses. However, targeting plasma membrane proteins essential for viral infection is challenging due to the transient nature of virus-cell binding and the dynamics of the infection process. The EU-funded COMBINE project will investigate the interaction between the highly pathogenic Marburg virus (MARV) and respective host cells. It will use an inverted attachment platform to halt virus infection at the cell binding stage, compatible with BSL-4 environments and multiomics technologies. This approach will identify proteins involved in virus entry in a tissue-specific manner. The project will integrate proteomics, virus-host interaction analysis and imaging techniques to pinpoint and characterise these proteins and their role in MARV infection.

Objective

Identifying cellular attachment factors and functional receptors plays a critical part in developing an understanding of a newly emerging virus. However, the identification and therapeutic targeting of plasma membrane proteins critical for virus infection is often difficult due to the transient nature of virus-cell binding and the overall kinetics of the infection process. Our goal is to interrogate virus-host cell interaction and cellular uptake of Marburg virus (MARV), a highly pathogenic and clinically relevant member of the filovirus family. To specifically target virus-plasma membrane interaction we will use a unifying inverted infection platform that allows us to halt and synchronize virus infection at the cell binding stage. Our approach is compatible with BSL-4 environment and multi-Omics technologies. It will allow us to identify the signature of virus-host cell activation, i.e. proteins involved in virus-cell entry in a tissue-specific manner. This screen will be complemented by an innovative combination of proteomics, virus-host cell interaction analysis and imaging approaches to pinpoint and characterize the involved cellular and viral proteins, their post-translational modifications and how they mechanistically concert in viral uptake. Our unique combination of different technologies will lead to the identification of viral and cellular interaction partners which will in parallel be specifically targeted by high-throughput compound screening to identify small molecules that inhibit virus-receptor interaction. Moreover, we will use our gained knowledge of tissue-specific post-translational modifications to develop improved vaccine candidates as additional prophylactic countermeasures against MARV. Our project will further deliver a blueprint experimental pipeline for the streamlined identification and antiviral targeting of proteins involved in the virus attachment process, a critical cornerstone of pandemic preparedness.

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Programme(s)

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Topic(s)

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Funding Scheme

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HORIZON-RIA - HORIZON Research and Innovation Actions

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Call for proposal

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(opens in new window) HORIZON-HLTH-2024-DISEASE-08

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Coordinator

HELMHOLTZ-ZENTRUM FUR INFEKTIONSFORSCHUNG GMBH
Net EU contribution

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.

€ 2 042 411,25
Address
INHOFFENSTRASSE 7
38124 Braunschweig
Germany

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Region
Niedersachsen Braunschweig Braunschweig, Kreisfreie Stadt
Activity type
Research Organisations
Links
Total cost

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.

€ 2 042 411,25

Participants (6)

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