How vitamins, steroids and potential antivirals can affect SARS-CoV-2

Evidence is emerging that vitamin D – and possibly vitamins K and A – can help fight COVID-19. A new study from the University of Bristol published in the journal of the German Chemical Society Angewandte Chemie showed how they – and other antiviral drugs – can work. Research indicates that these supplements and dietary compounds can bind to the peak viral protein and therefore reduce the infectivity of SARS-CoV-2. In contrast, cholesterol can increase infectivity, which could explain why having high cholesterol is considered a risk factor for serious illnesses.

Recently, researchers from Bristol showed that linoleic acid binds to a specific location in the viral peak protein and that in doing so, it blocks the peak in a closed and less infectious form. Now, a research team has used computational methods to search for other compounds that may have the same effect, such as potential treatments. They hope to prevent human cells from becoming infected, preventing the viral protein from opening up enough to interact with a human protein (ACE2). New antiviral drugs may take years to be designed, developed and tested, so the researchers looked at a library of approved drugs and vitamins to identify those that can bind to this newly discovered ‘drugstable bag’ within the SARS-CoV-2 spike protein.

The team first studied the effects of linoleic acid on the peak, using computer simulations to show that it stabilizes the closed form. Other simulations have shown that dexamethasone – which is an effective treatment for COVID-19 – can also bind to this location and help reduce viral infectivity, in addition to its effects on the human immune system.

The team ran simulations to see which other compounds bind to the fatty acid site. This identified some drugs that were found in experiments to be active against the virus, suggesting that this may be a mechanism by which they prevent viral replication, for example, blocking the peak structure in the same way as linoleic acid.

The findings suggested several drug candidates among pharmaceutical products and dietary components available, including some that delayed the reproduction of SARS-CoV-2 in the laboratory. They have the potential to bind to the SARS-CoV-2 spike protein and can help prevent cell entry.

The simulations also predicted that fat-soluble vitamins D, K and A bind to the peak in the same way, making the peak less capable of infecting cells.

Dr. Deborah Shoemark, Senior Associate Researcher (Biomolecular Modeling) at the School of Biochemistry, who modeled the peak, explained: “Our findings help explain how some vitamins can play a more direct role in combating COVID than their conventional support of human immune system.

“Obesity is an important risk factor for severe COVID. Vitamin D is fat-soluble and tends to accumulate in adipose tissue. This can reduce the amount of vitamin D available to obese individuals. Countries where some of these vitamin deficiencies are more common also suffered a lot during the course of the pandemic. Our research suggests that some essential vitamins and fatty acids, including linoleic acid, may contribute to preventing the peak / ACE2 interaction. . “

Elevated pre-existing cholesterol levels have been associated with an increased risk of severe COVID-19. Reports that the SARS-CoV-2 spike protein binds to cholesterol led the team to investigate whether it could bind to the fatty acid binding site. Their simulations indicate that it can bind, but it can have a destabilizing effect on the blocked peak conformation and favor the open and more infectious conformation.

Dr. Shoemark continued: “We know that the use of statins to lower cholesterol reduces the risk of developing severe COVID and shortens recovery time in less severe cases. Whether cholesterol destabilizes the” benign “closed conformation or not, our results suggest that by interacting directly with the peak, the virus could sequester cholesterol to reach the local concentrations necessary to facilitate entry into cells and this may also be responsible for the observed loss of circulating cholesterol after infection. “

Professor Adrian Mulholland of the Bristol School of Chemistry added: “Our simulations show how some molecules that bind to the linoleic acid site affect the peak dynamics and block it. They also show that drugs and vitamins active against the virus can work on it Targeting this location could be a route to new antiviral drugs. A next step would be to examine the effects of dietary supplements and test for viral replication in cells. “

Alison Derbenwick Miller, vice president of Oracle for Research, said: “It is incredibly exciting that researchers are gaining new insights into how SARS-CoV-2 interacts with human cells, which will eventually lead to new ways to combat COVID-19. I am delighted that Oracle’s high-performance cloud infrastructure is helping to advance this kind of research that changes the world. The growth of a globally connected community of cloud researchers is exactly what Oracle for Research was designed to do.