Presented as « a world first very promising« , a new step in understanding the mechanisms of entry of Covid-19 into cells has just been taken by researchers from UCLouvain. Not only have they managed to identify a new key that allows the famous virus to s attack the cells, but in addition, they managed to close the lock, so as to block the Covid-19 and avoid his interaction with the cell. In other words: they succeeded in preventing the infection, no more and no less.
Posted in NatureCommunicationsthis discovery « arouses great hope« , according to the UCLouvain team which aims in this case to develop an antiviral, probably in the form of an aerosol, which would make it possible to eradicate the virus in the event of infection. or high-risk contact.
Because indeed, there is to date no truly effective treatment against this coronavirus which always threatens to make a return in one form or another at some point. Well aware that the development of an antiviral to prevent infection inevitably requires a better understanding of the precise mechanisms (at the molecular level) used by the virus to infect a cell, the team of David Alsteens, researcher at the UCLouvain’s Institute of Biomolecular Sciences and Technologies has been working on this for two years. Using atomic force microscopy, scientists have investigated the interaction between sialic acids (AS), kinds of sugar residues present on the cell surface, and the Spike protein (S) of SARS-CoV-2. The objective pursued is to elucidate the role played in the infection process by this famous key which allows SARS-CoV‑2 to enter our cells.
The virus trapped
Until now, we knew that all cells are covered with sugar residues, whose role is to promote cell recognition. This allows viruses to identify their targets more easily but also facilitate their point of attachment to allow them to enter their host cell and thus initiate their infection.
Starting from there, the UCLouvain researchers have highlighted a variant of these sugars which interacts more strongly with the S protein than the other sugars. In pictorial language, they found the bunch of keys that allows viruses to open the cell door. Why a keychain? « Because the virus is made up of a series of spike proteins, sorts of suction cups that allow it to cling to the cell and ultimately enterthey explain. The more keys the virus finds, the better the interaction with the cell will be and the bigger the door will open. Hence the importance of finding how the virus manages to multiply the entry keys« .
Here comes the second discovery of researchers who wanted to catch the virus in its own trap, preventing it from clinging to its host cell. To do this, they blocked the attachment points of the protein S and thereby suppressed any interaction with the cell surface. « As if a padlock jammed the lock on the front door of the cell. To do this, one of the conditions is that the interaction between the virus and the blocking agent is stronger than that between the virus and the cell.« . In this precise case, « we demonstrated that multivalent structures (or glycoclusters) presenting multiple acids 9-O-acetylated sialics on their surface (the famous sugar variant updated by the UCLouvain team) are able to block both the binding and the infection of SARS-CoV-2comments David Alsteens. If the virus does not attach to the cells, it no longer knows how to enter and therefore it dies (the life time being from 1h to 5h)« . Thanks to this blocking, infection is prevented. CQFD.
And now?
This discovery has the advantage of acting on the virus, independently of the mutations, and is also interesting in the future, to counter other viruses. whose attachment factors are similar, further specifies the UCLouvain team, which will now carry out tests on mice for' »apply this blocking of virus links and observe if it works on the organism« .
According to the researchers, the results should not be long in coming and should eventually make it possible to develop an antiviral from these sugars, administered by aerosol, in the event of infection or contact at risk. Why aerosol? « Because the upper airways were more often the target of the later variants“, replies David Alsteens.
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