The COMBINE Project: Comparative Signature of Marburg Virus Cell Activation as a Blueprint for the Identification of Antiviral Targets against Newly Emerging Viruses

Overall COMBINE Objectives:

• COMBINE aims to elucidate how Marburg virus (MARV) interacts with host cell factors during initial attachment, focusing on tissue-specific variations to identify potential receptors that mediate viral entry across different tissues.
• COMBINE will characterize tissue-specific post-translational modifications (PTMs) of the MARV glycoprotein and host cell surface proteins, elucidating how these modifications influence viral attachment, receptor interactions, tissue tropism, immune evasion, replication, and adaptation to new host environments.
• COMBINE will use advanced microscopy, single-virus tracking, and multicolor imaging to investigate the spatial organization and infection-induced responses of identified host cell proteins in living target cells, elucidating the dynamic sequence of MARV entry from initial attachment and receptor activation to cellular uptake.
• COMBINE will leverage its insights into virus–host interactions to identify small molecules and synergistic combinations targeting distinct MARV entry pathways, while informing the design of improved, broadly protective vaccine candidates capable of eliciting robust antibody and T-cell responses