Over just a few weeks, COVID-19 has been ‘invited’ into several research projects at UCLouvain, particularly at the Centre for Applied Molecular Technologies (CTMA), where half a dozen preventive, diagnostic or therapeutic studies are already underway.
Unknown six months ago, the now infamous coronavirus that first appeared in 2019 (COVID-19) isn’t finished making waves—literally. As Europe could be in the undertow of the pandemic’s potential second wave,1 many unknowns and uncertainties surround the new coronavirus. Its modes of transmission, how to detect, counter and prevent it – thousands of researchers the world over are trying to find out more about it. UCLouvain is participating in this effort by launching or participating in many Belgian and international projects related to COVID-19.
Finding new treatments?
At the CTMA, several preventive, diagnostic or therapeutic research projects have been initiated. At the therapeutic level, Anandi Martin, a tuberculosis specialist, examines the antiviral properties of certain bacteriocins. The project is carried out with the firm Syngulon.
Collecting neutralising COVID-19 antibodies is the starting point of several studies. In fact, some 30 volunteers identified by the CTMA and now recovered from COVID-19 have agreed to provide blood samples. With the participation of the Red Cross, the researchers first extract the antibody-producing cells that volunteers’ immune systems have made to fight the coronavirus. Next, cloning the antibody production mechanism will allow the production of antibodies in large quantities. The stock of neutralising antibodies is intended to treat severe cases of COVID-19 as a replacement for plasmapheresis. Indeed, the logistics of setting up and using plasmapheresis are very cumbersome and not applicable on a large scale.
Improving COVID-19 diagnostic tests
Neutralising antibodies could be of interest at the diagnostic level as well. They will be used in an attempt to improve the performance of detection tests. ‘Currently, no diagnostic test is 100% reliable,’ says Jean-Luc Gala, a professor of molecular biology and the CTMA director. ‘A Win2Wal project aims to compare a test validated and used around the world (but not in Belgium) with potential new second, third, and fourth-generation tests. In addition to the neutralising antibodies, the project assesses the value of camelid antibodies or “nanobodies” and aptamers.’2
- Nanobodies, which are produced by immunising llamas or camels, recognise antigens in a very specific and particularly detailed way.
- Aptamers are short pieces of synthetic DNA or RNA (oligonucleotide) that can bind specifically to an antigen.
A preventative project
At the preventative level, CTMA researchers want to create a bank of peptidomimetic agents. ‘Viruses have to attach to receptors in a cell in order to infect it,’ Prof. Gala explains. ‘We’re looking to develop decoys, synthetic peptides that mimic these cellular receptors. The virus would then attach itself to them and leave the host's cells alone. Using biocomputing tools, we’re in the process of determining the best “shape” to give these peptidomimetic agents so that they effectively deceive the virus.’ If successful, the approach would pave the way for preventative treatment of COVID-19.
Understanding the dreaded ‘inflammatory storms’
Some people with COVID-19 experience a ‘cytokine storm’ or inflammation. It results from over-stimulation of the immune system. ‘The cytokine storm is an uncontrolled disproportionate immune response and responds poorly to treatment,’ Prof. Gala says. ‘In response to the coronavirus, the immune system goes berserk. It releases proinflammatory cytokines en masse, particularly in the lungs. This violent pulmonary inflammatory response can be life-threatening and often requires admission to intensive care.’
The CTMA has submitted an FNRS research proposal which aims to understand the mechanisms of the cytokine storm, by studying the genetic profiles of patients’ blood cells and comparing them with the pathogenicity of Belgian coronavirus clusters.
Other projects related to logistics and practical techniques and tools to detect or neutralise the novel coronavirus are also underway at CTMA.
Notes
(1) It is not yet clear whether the pandemic will cause a second wave, and if so, how significant it will be.
(2) The Walloon Region’s Win2Wal programme finances innovative research projects.
The CTMA’s ‘matrix’ approach
The CTMA organises its research projects in a ‘matrix’. The same theme or work subject (here COVID-19) is explored in a transversal way by several researchers, in different fields, which often overlap or complement one another. There is also a close interconnection of regional, federal, European and international projects. ‘Through this matrix, nesting doll approach, we were able to quickly reorient, complete or initiate research relating to the new coronavirus,’ Prof. Gala explains. ‘Everything we do on it is part of pre-COVID-19 projects, expertise that we already had and with known industrial partners.’
Candice Leblanc
Jean-Luc Gala's bio
Jean-Luc Gala is professor of biomedical sciences at UCLouvain, clinical director at Saint-Luc University Hospital, and director of the CTMA. He holds a master’s degree in medicine and a PhD in biomedical sciences, obtained respectively in 1984 and 1997 at UCLouvain. Specialising in internal medicine (haematology) since 1990, he has spent a good part of his career in the medical service of the Armed Forces. He has become one of Belgium’s experts in the field of identification and control of biological weapons (1990-2016). In 2003, he founded a military unit responsible for the detection, identification and characterisation of ‘bioterrorism agents’. In 2006, he integrated this unit into the CTMA/UCLouvain via a framework agreement between UCLouvain and the Ministry of Defence. This makes the CTMA a military, clinical and academic biotechnology platform unique in Belgium.