22nd Sep 2020
22nd Sep 2020
Curated by Endre Szvetnik
Scientists have discovered an area on the notorious SARS-CoV-2 spike protein that could be used to disable the virus. The finding opens the way to create small-molecule drugs that could help treat the disease.
The team at the University of Bristol was surprised to chance upon a previously unknown ‘pocket’ that could prevent the virus from docking with human cells using its spike protein, if targeted with new drugs. The ‘handshake’ between the spike and human cell receptors is the first step in a potentially devastating process of infection. The scientists have found that the ‘pocket’ in the structure of the spike that harbours free fatty acids, such as linoleic acid (LA), an essential small molecule.
Linoleic acid is a fatty acid, not produced by the human body that can help disable the spike protein. The team has found that when something occupies the linoleic acid-binding pocket, the spike protein is unable to dock with human cell receptors, so it can’t spread infection. LA is also important to many cellular functions. For example, it helps maintain the membranes of lung cells. We can obtain this molecule through our diet. In the context of COVID-19, the lack of or depleted levels of LA were detected in patients suffering from severe disease. The reason for this is because the acid plays an important role in inflammation and in regulating the balance of different immune cells that both malfunction in severe COVID-19.
The researchers froze the SARS-CoV-2 spike molecules and then observed them with powerful cryo-electron microscopes which provide very high magnification and allow to see individual molecules. They recorded a multitude of clips of the spike from different angles and used powerful cloud computing, to create a 3D model of the spike. With this, they managed to determine the structure of the spike protein and come across the pocket that can be its weak point.
The next step is to find the molecules that bind to the pocket and switch off the viral spike. This has been done before: researchers have created molecules that tightly covered a ‘pocket’ of the common cold-causing rhinovirus. The molecules performed well in clinical trials but there isn’t any inhibitor drug on the market yet that is based on them. The recent discovery about the spike protein could offer a new way to suppress SARS-CoV-2 in the absence of a vaccine, but there is much work remaining for to create an effective drug.
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