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Researchers have discovered a pocket in the Pico protein of SARS-CoV-2, which they say could be a drug target for COVID-19.
Researchers have discovered a potentially junkie pocket in the SARS-CoV-2 Spike (S) protein. According to the team, from the University of Bristol, UK, drugging this pocket could prevent the virus from infecting human cells.
The researchers explain that the surface of SARS-CoV-2 is covered by multiple copies of glycoprotein S, which plays an essential role in viral infectivity. Protein S binds to the surface of the human cell, allowing the virus to penetrate cells and begin to replicate, causing widespread damage.
In this study, the team used an imaging technique called cryogenic electron microscopy (cryo-EM) to analyze the SARS-CoV-2 S protein at near-atomic resolution. Enabled by Oracle’s high-performance cloud computing, a three-dimensional (3D) structure of protein S was generated, allowing researchers to understand its molecular makeup.
Analysis revealed the presence of a small molecule, linoleic acid (LA), within a pocket in the SARS-CoV-2 S protein. LA is a free fatty acid that is essential for many cellular functions, but the human body does not. can produce LA. Instead, the body absorbs this essential molecule through diet. The molecule is also required to keep the cell membranes in the lungs to breathe.
One of the principal investigators, Professor Imre Berger, said: “We were truly puzzled by our discovery and its implications. So here we have LA, a molecule that is at the center of those functions that go haywire in COVID-19 patients, with dire consequences. And the virus that is causing all this chaos, according to our data, grabs and latches on exactly to this molecule, basically disarming much of the body’s defenses. “
Another lead researcher, Professor Christiane Schaffitzel, explained: “From other diseases we know that manipulating the metabolic pathways of LA can trigger systemic inflammation, acute respiratory distress syndrome (ARDS) and pneumonia. All of these pathologies are seen in patients with severe COVID-19. A recent study of patients with SARS-CoV-2 showed markedly reduced LA levels in their sera ”.
Professor Berger added: “Our discovery provides the first direct link between the pathological manifestations of LA, COVID-19 and the virus itself. The question now is how to turn this new knowledge against the virus itself and defeat the pandemic. “
The researchers say that with the rhinovirus, which causes the common cold, a similar pocket was exploded to develop powerful little molecules that bound tightly to the pocket, distorting the structure of the rhinovirus and stopping its infectivity. These small molecules have been used successfully as antiviral drugs in human trials and show promise for the clinical treatment of rhinovirus. The Bristol team, based on their data, is optimistic that a similar strategy can now be followed to develop small molecule antiviral drugs against SARS-CoV-2.
“COVID-19 continues to cause widespread devastation and, in the absence of a proven vaccine, it is vital that we also look for other ways to combat the disease … Our discovery of a drug pocket within the SARS-CoV-2 S protein could lead to new antiviral drugs to turn off and eliminate the virus before it enters human cells, firmly stopping it in its tracks, ”said Professor Schaffitzel.
He was published in Sciences
