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Research project

Finding novel routes to penetrate the mycetoma grain (PENEGRAIN)

Status: Ongoing project, start date: 2024; end date: 2029

The tropical disease mycetoma can be caused by bacteria or fungi. Characteristic of this disease is the formation of a shield by the pathogens which protect them against drugs. This makes this disease untreatable. PENEGRAIN is an open science project in which scientists and laymen will collaborate to open up this shield. We will create novel models which we will use to determine how this shield is created and which drugs and carriers can penetrate. This research will lead to novel drugs which can be used not only for mycetoma but also for other difficult to treat infections.

Contact

What we do

About our project

Penegrain

PENEGRAIN is an open science project in which scientists and laymen will collaborate to open up this shield. We will create novel models which we will use to determine how this shield is created and which drugs and carriers can penetrate. PENEGRAIN is a subproject of the Mycetoma Open Source drug discovery project MycetOS.

MycetOS

MycetOS is an Open Source drug discovery project which uses an Open Pharma approach to discover new chemical entities for mycetoma caused by Madurella mycetomatis, the main causative agent of fungal mycetoma. The project will identify novel lead compounds to treat mycetoma.

Open Source

The project uses an open approach which means that the it will progress discovery efforts through community-driven and in kind scientific contributions. Compounds are donated and are tested for in vitro activity in our laboratory. Results will be published immediately in real time in an open-access database.

Results so far

In this project we have screened the pathogen, stasis, pandemic and COVID boxes from MMV and identified the fenarimol compounds and benzimidazoles as potent anti-mycetoma agents. More recently we also kinases libraries and the oncode library to identify more potent anti-mycetoma compounds. Online discussions are ongoing to determine which compound libraries we should screen next. 

MycetOS logo

 

Our research focus

Fenarimols

In this project we demonstrated that the fenarimol compounds were potent inhibitors of M. mycetomatis growth. However not all compounds were able to penetrate the mycetoma grain. Therefore additional fenarimol analogues are being screened to determine the chemical properties needed for a molecule to penetrate the mycetoma grain. This information will help us in designing effective drugs for mycetoma.

Other compounds

Next to the fenarimol analogues, several other compounds were able to inhibit M. mycetomatis growth or penetrate the grain. Compound libraries are currently sought of these compounds to assess which compounds are most effective in penetrating mycetoma grains.

Participation

Since this project is an Open Source project, it means that everybody interested in drug discovery can participate. Via our GitHub page you can participate in our online discussions, see the results and propose novel compounds to be screened.

 

Funds & Grants

This project has been funded by ErasmusMC grants and most recently by a VICI grant from NWO.

Collaborations

  • Professor Matthew H. TOdd, PhD,
    Chair of Drug Discovery,
    School of Pharmacy,
    University College Londen,
    United Kingdom
  • Jean-Robert Ioset, PhD,
    Drugs for Neglected Diseases initiative,
    Geneva,
    Switzerland

Publications

Lim W., Melse Y., Konings M., Phat Duong H., Eadie K., Laleu B., Todd M.H., Ioset J.R., van de Sande W.W.J. (2018) Addressing the most neglected diseases through an open research model: The discovery of fenarimols as novel drug candidates for eumycetoma. PLoS Negl Trop Dis 12(4):e0006437

Our team

Principal investigator

Team members