COMBINE

With the emergence of viral diseases expected to accelerate, preparing for future pandemics is crucial. A key step in combating emerging infectious diseases is understanding how viruses invade host cells. COMBINE focuses on the critical virus-cell binding step, aiming to identify key factors and potential therapeutic targets involved in the early stages of viral infection. Using the Marburg Virus (MARV) as a model, the project seeks to deepen our understanding of virus entry into cells, examining virus-host interactions and cellular uptake. This novel approach distinguishes between the initial attachment of the virus and subsequent processes such as cellular activation and internalisation.

COMBINE applies a combination of pioneering approaches designed to identify the signature of virus-cell activation (i.e., plasma membrane attachment factors and functional receptors involved in virus-cell entry in a tissue-specific manner), and to characterise the mechanisms of virus binding and entry. The gained knowledge of tissue-specific post-translational modifications is used to develop novel inhibitors and improved vaccine candidates as additional prophylactic countermeasures against MARV. Moreover, COMBINE will not only reveal new insights on MARV cell entry and tissue tropism but 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.