Project

Work Package 1 - BSL4 Virology

Work Package 1 provides samples from authentic MARV-infected cells and optimizes a BSL2 life cycle model system for MARV. This Work Package also validates the neutralising activity of identified small molecules and peptides against authentic MARV and tests novel viral epitopes as potential antigens for vaccine development – supporting therapeutic and vaccine candidate development for MARV.

Work Package 2 - Identification of the signature of MARV – host cell interaction

Work Package 2 focuses on identifying tissue-specific post-translational modification (PTM) profiles of MARV and characterising tissue-specific host surfaceomes. Furthermore, this Work Package investigates the host signalling networks activated by MARV and identifies host proteins involved in the virus’s attachment to and entry into host cells, advancing our understanding of MARV infection mechanisms and identify potential therapeutic targets.

Work Package 3 - AI-based data exploration and integration for detailed hypothesis generation

Work Package 3 conducts an integrative analysis of the virus and host proteomes, focusing on post-translational modifications (PTMs), integrating proteomics data into a network of PTM-dependent protein associations and conducting tissue-specificity analysis to predict susceptibility based on modified proteins. The findings and models will be shared through online knowledgebases and software tools for broader use.

Work Package 4 - High-throughput MARV – receptor interaction analysis

In Work Package 4, a platform to study the direct interaction between MARV glycoproteins (GP) and host cell proteins will be established. Furthermore, a comprehensive list of proteins and their post-translational modifications (PTMs) involved in MARV-host cell binding and the inhibitory effects of compounds and antibodies on MARV GP- host cell protein interaction will be validated.

Work Package 5 - Virus-protein interaction and virus uptake studied at the single-virus level

This Work Package investigates the mechanisms behind MARV cell entry, including the kinetics of viral uptake and the impact of MARV binding on host protein organisation and diffusion. Furthermore, WP 5 investigates the role of viral post-translational modifications (PTMs) in virus-host interactions and viral entry processes.

Work Package 6 - Identification of small molecules that inhibit cellular uptake of MARV and of antigen candidates for the development of improved MARV vaccines

Work Package 6 aims to improve both antiviral therapies and vaccine development for MARV by identifying small molecules that block viral entry into host cells, disrupting key viral-host interactions, and targeting protein-protein and lipid-receptor interactions. Additionally, this Work Package is optimising potential vaccine candidates by identifying relevant epitopes and antigens.

Work Package 7 - Innovation Management: Communication, Dissemination, Exploitation

Innovation management will ensure consistent communication and dissemination, assuring optimal visibility and a wide outreach to relevant stakeholders. Strategic planning and implementation of project exploitation will safeguard that high-quality results are captured, assessed and used. A proper IP management strategy will lay the foundation for further exploitation and sustainability.

Work Package 8 - Project management and scientific coordination

Work Package 8 provides a clear organizational framework, guidance and all support mechanisms to enable a smooth project workflow in COMBINE to ensure that objectives and milestones will be met in time.