![]() If we look at HIV, after 30 years of research what worked in the end is a cocktail of small molecule anti-viral drugs that keeps the virus at bay. Professor Schaffitzel said: "COVID-19 continues to cause widespread devastation and in the absence of a proven vaccine, it is vital that we also look at other ways to combat the disease. The Bristol team, based on their data, is optimistic that a similar strategy can now be pursued to develop small molecule anti-viral drugs against SARS-CoV-2. These small molecules were successfully used as anti-viral drugs in human trials and show promise for treating rhinovirus clinically. ![]() In rhinovirus, a virus causing the common cold, a similar pocket was exploited to develop potent small molecules that bound tightly to the pocket distorting the structure of the rhinovirus, stopping its infectivity. The question now is how to turn this new knowledge against the virus itself and defeat the pandemic." Professor Berger adds: "Our discovery provides the first direct link between LA, COVID-19 pathological manifestations and the virus itself. A recent study of COVID-19 patients showed markedly reduced LA levels in their sera." These pathologies are all observed in patients suffering from severe COVID-19. Professor Schaffitzel explained: "From other diseases we know that tinkering with LA metabolic pathways can trigger systemic inflammation, acute respiratory distress syndrome and pneumonia. And the virus that is causing all this chaos, according to our data, grabs and holds on to exactly this molecule – basically disarming much of the body's defences." So here we have LA, a molecule which is at the centre of those functions that go haywire in COVID-19 patients, with terrible consequences. Professor Berger said: "We were truly puzzled by our discovery, and its implications. LA is also needed to maintain cell membranes in the lungs so that we can breathe properly. Intriguingly, LA plays a vital role in inflammation and immune modulation, which are both key elements of COVID-19 disease progression. Instead, the body absorbs this essential molecule through diet. LA is a free fatty acid, which is indispensable for many cellular functions. Unexpectedly, the research team’s analysis revealed the presence of a small molecule, linoleic acid (LA), buried in a tailor-made pocket within the Spike protein. Enabled by Oracle high-performance cloud computing, a 3D structure of SARS CoV-2 Spike protein was generated allowing the researchers to peer deep inside the Spike identifying its molecular composition. In this ground-breaking study, the team headed by Professor Christiane Schaffitzel from Bristol’s School of Biochemistry and Professor Imre Berger from the Max Planck-Bristol Centre for Minimal Biology, used a powerful imaging technique, electron cryo-microscopy (cryo-EM), to analyse SARS-CoV-2 Spike at near atomic resolution. Spike binds to the human cell surface, allowing the virus to penetrate the cells and start replicating, causing widespread damage. SARS-CoV-2 is decorated by multiple copies of a glycoprotein, known as the 'Spike protein', which plays an essential role in viral infectivity.
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