MATRIXCURE-2: Structure-based drug design against Sudan virus infections : Date:
The GO-Bio initial project MATRIXCURE-2 develops novel low-molecular-weight active substances against the Sudan virus (SUDV), an orthoebolavirus. The focus is on the targeted inhibition of the viral matrix protein VP40 as a key target for antiviral therapy.
Urgent need for antiviral treatments
Ebola viruses cause extremely severe febrile illnesses, with around half of all patients dying as a result. Ebola viruses pose a significant threat to public health, particularly in Central Africa. Recurring outbreaks, transmission via infected animals and increasing global mobility are heightening the wide-spread risk of the viruses. Despite the availability of vaccines and monoclonal antibodies against the Zaire Ebola virus, there remain therapeutic gaps for other Orthoebolavirus species, in particular the Sudan virus (SUDV). Infections with the Sudan virus present with symptoms similar to those of Ebola virus disease and are also associated with a high case fatality rate. As there are no specific treatment options, management is largely limited to supportive care.
A key objective of antiviral research is to identify stable viral target structures that are suitable for drug-based therapy. The MATRIXCURE-2 project focuses on the matrix protein VP40, which plays a crucial role in viral replication and the release of Sudan virus particles from the infected cell. Inhibiting VP40 would mean that the Sudan virus remains trapped within the cell.
Structure-guided drug design against VP40
The project builds on a crystallography-based fragment screening, in which around 50 low-molecular-weight compounds were identified that bind specifically to VP40. These lead compounds have been further developed through medicinal chemistry and, in initial studies, have demonstrated promising antiviral activity as well as high target structure specificity.
The aim of the current development phase is the preclinical validation of these VP40 inhibitors. This involves systematically investigating the active substances for their antiviral efficacy and pharmacological properties.
The work is carried out in close collaboration between two specialist research groups: one group focuses on the chemical optimisation of the lead compounds, whilst the second group is responsible for virological testing in cell culture and animal models. This is complemented by expertise in the fields of drug design, pharmacokinetics and virology.
The long-term aim is to achieve preclinical proof of principle, which will serve as the basis for further development steps, potential patenting and subsequent translation into drug development.
To learn more about funded GO-Bio projects, visit the overview page.