COMBINE logo-whiteTowards Improved Pandemic Preparedness
Advancing Our Understanding of Virus Cell Entry Using Marburg virus as a Model
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Bluesky

Publications

2025

Public Deliverables

  • D6.1 GP – Host cell inhibition
    Published December 2025, Public
    • Executive Summary

      Work package 6 comprises the identification of small molecules that inhibit cellular uptake of Marburg Virus (MARV) and of antigen candidates for the development of improved MARV vaccines. In order to establish a working pipeline against MARV and future viral threats, a key step is the opportunity to screen large amounts of possible drug candidates in a reasonable short amount of time. Therefore, a robust automated screening protocol needs to be established. Since MARV and host cells interact via different viral ligand - host receptor pairs, different setups with minor adaptations to the original screening assay will be needed, in order to address the diverse targeted interactions. In more detail, we will search for phosphatidylserine (PS) to PS-receptor inhibitors, first in Huh-7 cells expressing TIM-1. Further we will investigate the binding of glycoproteins (GP) and lectins (e.g. DC-SIGN). The last approach comprises new possible MARV GP target sides which will be identified during the project and we will search for inhibitors of such protein – protein interactions. The aim of the first year within WP6 was the establishment of a screening protocol, that is feasible, practicable and versatile for the identification of MARV entry inhibitors. The results obtained from the different screening campaigns will be used by other members of the consortium to establish better models and to develop new structure-optimized inhibitors. All compounds which show an inhibitory effect within the initial BSL-2 surrogate system will be evaluated with authentic MARV under BSL-4 conditions.