Evidence suggests that vitamin D – and possibly vitamins K and A – may help fight COVID-19. A new study from Bristol University published in the journal German Chemical Society Angewandte Chemie has shown how they – and other antiviral drugs – can work.
The research shows that these diet and fertilizer products may bind to the viral spike protein and thus may reduce SARS-CoV-2 infection. In contrast, cholesterol may increase infectivity, which may explain why high cholesterol is considered a risk factor for serious disease.
Recently, researchers from Bristol showed that linoleic acid binds to a specific site in the viral spike protein, and in doing so, locks the spike in a closed, less infectious form. . Now, a research team has used computer techniques to find other compounds that may have the same effect, such as potential treatments.
They hope to prevent human cells from inhibiting the viral spike protein from opening sufficiently to interact with human protein (ACE2). New antiviral drugs can take years to design, develop and test, so the researchers looked through a library of approved drugs and vitamins to find those that could be linked to the virus. pocket of this recently discovered drug inside the SARS-CoV-2 spike protein.
The team first studied the effect of linoleic acid on the spike, using computer simulations to show that it stabilizes the closed form. Further indications showed that dexamethasone – which is an effective treatment for COVID-19 – may also link to this site and help reduce viral infections as well as its impact on the human immune system.
The team then made simulations to see what other fertilizers bind to the fatty acid site. This identified some drugs found by experiments to be active against the virus, suggesting that this may be one way in which they prevent such viral reproduction, by blocking the spike structure in the same way as linoleic acid.
The findings suggested several drug candidates among available pharmaceutical and diet products, including some that were found to delay laboratory SARS-CoV-2 reproduction. These have the ability to bind to the spike protein SARS-CoV-2 and may help prevent cell entry.
The simulations also predicted that the fat-soluble vitamins D, K and A would bind to the spike in the same way making the spike less able to capture cells.
Dr Deborah Shoemark, Senior Research Associate (Biomolecular Modeling) in the School of Biochemistry, who was a model on the spike, explained:
Our findings help explain how some vitamins may play a more direct role in fighting COVID than normal support for the human immune system.
Obesity is a major risk factor for true COVID. Vitamin D is present in fat and tends to accumulate in fat. This can reduce the amount of vitamin D available to obese people. Countries where some of these vitamin deficiencies are more prevalent have also suffered severely from the pandemic. Our research suggests that some vitamins and fatty acids containing linoleic acid may contribute to inhibition of spike / ACE2 interactions. Deficiency in any of them may make it easier for the virus to become infected. “
Previous high cholesterol levels have been associated with an increased risk for severe COVID-19. Reports that the cholesterol-binding protein SARS-CoV-2 spike protein prompted the team to investigate whether it could bind at the fatty acid-binding site. Their symbols indicate that it may bind, but that it may have an unstable effect on the locking concord of the spike, and favors the open, more contagious concord.
Dr Shoemark continued: “We know that the use of cholesterol-lowering statins reduces the risk of developing severe COVID and shortens recovery time in less severe cases. Whether cholesterol uninstalling the “incompetent”, closed concordance or not, our results suggest that by interacting directly with the spike, the virus could trap cholesterol to the concentrations needed to achieve cell entry and this may also account for the perceived loss of circulating cholesterol after infection. “
Professor Adrian Mulholland, of Bristol School of Chemistry, said: “Our simulations show how some molecules bound at the site of linoleic acid affect the dynamics of the spike and lock it in. They also shows that drugs and vitamins that are active against the virus may work in the same way Targeting this site may be a new path antiviral drugs. The next step is to look at the effects of diet and test products viral reproduction in cells.“
Alison Derbenwick Miller, Vice President, Oracle for Research, said:
Interestingly, researchers are gaining new insights into how SARS-CoV-2 interacts with human cells, which will eventually lead to new ways to fight COVID-19. . We are thrilled that Oracle’s high-performance cloud infrastructure is helping to advance this kind of world-changing scrutiny. Growing a connected global community of cloud-powered researchers is exactly what Oracle for Research is designed to do. “
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Magazine Reference:
Footprint, DK, et al. (2020) Molecular models suggest vitamins, retinoids and steroids as ligands bind a fat-free acid pocket of SARS-CoV-2 spike protein. Angewandte Chemistry. doi.org/10.1002/anie.202015639.