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[Article series] The experts behind Luxembourg's COVID-19 fight

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Published on Tuesday, 16 June 2020

Daniel Abankwa, Professor within the Department of Life Sciences and Medicine at the University of Luxembourg, is co-principal investigator of the COVID-19 research project "CovScreen: Combined In Silico Molecular Docking And In Vitro Experimental Assessment Of Drug Repurposing Candidates For Covid-19”.

The project, funded by the Luxembourg National Research Fund (FNR), will provide a fast experimental validation of drug repurposing candidates for COVID-19 from a computational pre-selection of antivirals, drugs and natural compounds that are inexpensive, have known safety properties and high predicted bioavailability in the lung.

Prof. Daniel Abankwa explains the project CovScreen in more details.

1)    Could you tell us more about your background and expertise?

Since September 2017, I am professor at the Department of Life Sciences and Medicine. Given my background in chemistry, neurobiology and cell biology, we are multidisciplinary in our approaches, for example by collaborating with physicists and chemists. The focus of my research group is on the most frequently mutated oncogene RAS. After 30 years of research, the first RAS drugs are currently being tested in humans. My research group is interested in how RAS drives the emergence of those first special cells that give rise to a full tumour. We are actively developing drugs to eRASe cancer. We have recently gained a total of €1.2 million competitive funding from the FNR for three cancer related bilateral research projects that will commence in fall. 

2)    How is your expertise relevant in the current COVID context? 

For our drug development projects we are regularly developing drug screening assays. These are experiments, where with as little material and as much sensitivity as possible we observe activities of hundreds to thousands of drugs. We look for example at the binding of the drug to the target molecule, e.g. a virus protein. We are very experienced in designing assays that test activities not only outside, but also inside of cells. This is important, because not every drug that works in the test tube, can actually effectively penetrate into a cell. Given that the analysis principles can be applied to basically any target, we are able to also look at drug targets that are new to us, such as those relevant to fight SARS-CoV-2. 

3)    What is your specific role in ongoing COVID projects? 

In a collaboration with Prof. Enrico Glaab from the Luxembourg Centre for Systems Biomedicine (LCSB), we are looking for new drugs that can inhibit proteases. These are enzymes that cleave other proteins, which can activate or modify them. In our particular case we are looking at one protease from the virus, called 3CLpro, which is needed for making viral proteins. Another one found in humans, called TMPRSS2, activates a surface protein of the virus for entry into human cells. Enrico will conduct computational screening against these targets, thus testing >200 millions of compounds in a rather short and very cost-efficient manner. However, computational data are just a first hint for a potential binder and we need to confirm a lot of activity in our ‘wet lab’ experiments. We will therefore take the selection of the best binders he identified (hits) and test them against the drug targets. Our particular goal is to identify inexpensive inhibitors, which are hopefully already approved for use in humans, and could then be used all across the world in particular in poorer communities. 

4)    Could you tell us more about your collaborators?

In our project CovScreen, we are collaborating with Prof. Enrico Glaab, who is an expert in computational biology. Within my research group, I have two excellent scientists working on the project: Dr. Ganesh Manoharan and Marie Catillon. They are very experienced in developing screening assays and working with proteins, respectively. Both are dropping their currently active projects in order to get our screening assays on track as soon as possible. Just getting the necessary materials aboard can be a bit lengthy, taking 3-4 weeks, but hopefully we can soon get started.

Once we are successful, we will have to approach expert virus researchers for testing on the actual virus infection process. Luckily, many of these experts are working not too far away, such as in Germany. It may also be significant to undertake some lobbying for the production of cheap medication.