How does the new coronavirus enter our cells and how do we keep it from entering? The team of David Alsteens (LIBST) will tackle these two questions with the help of state-of-the-art equipment, the atomic force microscope, and expertise on the interactions between viruses and their host cells. Their expertise has been recognised and developed over several years in the framework of an ERC Starting Grant.
A virus, by definition, doesn’t survive without ‘parasitising’ the cells of a living organism. It’s a non-living entity composed of genetic material (DNA or RNA) within a protective envelope which also plays the role of ‘Velcro’, to adhere to cells and allow the virus to enter them. The virus then hijacks cellular machinery to its advantage to multiply and infect other cells. The ‘Velcro’ is made up of proteins which bind to other proteins on the virus’s host cells.
In the case of SARS-CoV-2, which is responsible for the current COVID-19 pandemic, the protein involved in this adhesion has been identified: a spike-shaped protein on the coronavirus surface, called a ‘spike’ or ‘S protein’, binds to the ACE2 receptor in our cells. Typically, this receptor – found on the surface of some of our cells – is used to pass along a molecule involved in vasodilation. So it's a bit like the virus secured a key to open a lock, here the ACE2 receptor, giving access to the interior of our cells. The ACE2 receptor was already known to be the way in for other coronaviruses. We now know that this is also the case for SARS-CoV-2. Therefore, research teams are studying the link between the S protein of the new coronavirus and the ACE2 receptor to understand how it works and how to stop it.
No entry, no infection
Prof. Alsteens’s team is specialised in using an atomic force microscope to study interactions between viruses and host cells. ‘This equipment allows us to manipulate only one virus at a time, to place it on living cell receptors and pull on it to see how it attaches to the cell surface’, says Prof. Alsteens, a researcher at the Louvain Institute of Biomolecular Science and Technology. ‘We can thus measure the strength of the anchor links, the number of links, and the speed at which linkages take place. We can even go so far as to see how the virus sends a signal to be able to enter the cell. We developed this expertise over four years at UCLouvain. With the new coronavirus’s arrival we said to ourselves that we should do something to help understand its binding mechanism to cells and how it can enter. Often we’re able to determine which molecules of the virus and which cells interact significantly. And depending on the characteristics of these links, we can develop molecules that can prevent the interactions and make the virus bind less to the cell surface. If it binds less, we can hope there will be less infection.’ Because as is the case on any surface, the virus can’t survive in the human body if it can’t enter a cell.
Time, luck, and complementarity
As with every avenue explored in the fight against COVID-19, the question on everyone’s lips is how long it will take to get results. ‘The problem is that everything is slowing down a bit to respect social distancing measures within the laboratory’, Prof. Alsteens explains. ‘Usually, I put four or five researchers on this type of project, but at the moment only one person is working on it. We may put a second person on it if possible. And then there’s luck. Here, the crystalline structure, that is, the nesting between the virus’s ‘spike’ and the cellular receptor, is already known, so we can get an idea of the crucial links. We've already developed molecules to prevent them. We’ll test them in the coming weeks. It can go fast or slow, it's very difficult to say.’ We must therefore let research work at its own pace and rely on luck. If Prof. Alsteens's team succeeds in highlighting one or more molecules, making it possible to prevent the new coronavirus from entering our cells, they could be used in addition to antivirals or other drugs which target them, and stop the virus from multiplying inside cells. In the face of this new virus, all avenues are open for exploration, and our experts have strength in numbers and interdisciplinarity.
More information on research by David Alsteens’s team:
>>Corps à corps moléculaire
>>Examining molecular mechanisms to target treatments more effectively
>>Reoviruses: weapons against cancer?
>>When the virus ‘velcros’ to a cell
>>Martin Delguste, finaliste de MT180 2018
A glance at David Alsteens' bio
David Alsteens is an FNRS research associate and head of UCLouvain's NanoBiophysics Lab. He holds a master's degree in chemical engineering and bio-industry and a PhD in bioengineering, obtained in 2007 and 2011 respectively at UCLouvain. His PhD thesis received an award from the Royal Belgian Society for Microscopy.
An FNRS researcher at UCLouvain since 2011, he also spent two years (2013-15) at the Swiss Federal Institute of Technology in Zurich (Switzerland). His research has been financed mainly by a 2017 ERC Starting Grant (Europe), Welbio funding (Walloon Region) obtained in 2019, the FNRS and UCLouvain.