A new study has indicated that some vitamins, steroids, and antivirals may effectively help to combat COVID-19 by binding to the spike protein and inhibiting virus infectivity.
As evidence is emerging that vitamin supplements such as vitamin D, and possibly vitamins K and A, might help combat COVID-19, a new study undertaken by the University of Bristol has shown how these dietary supplements and compounds could bind to the viral spike protein and reduce SARS-CoV-2 infectivity. The study also indicates that cholesterol may increase infectivity, which could explain why having high cholesterol is considered a risk factor for serious disease.
The study has been published in the journal of the German Chemical Society Angewandte Chemie.
Recently, Bristol researchers showed that linoleic acid binds to a specific site in the viral spike protein, and that by doing so, it locks the spike into a closed, less infective form. Now, a research team has used computational methods to search for other compounds that might have the same effect, as potential treatments.
The team hope to prevent human cells becoming infected by preventing the viral spike protein from opening enough to interact with a human protein (ACE2).
The team first studied the effects of linoleic acid on the spike, using computational simulations to show that it stabilizes the closed form. Further simulations showed that dexamethasone – which is an effective treatment for COVID-19 – might also bind to this site and help reduce viral infectivity in addition to its effects on the human immune system.
Further simulations suggested several drug candidates among available pharmaceuticals and dietary components, including some that have been found to slow SARS-CoV-2 reproduction in the laboratory, have the potential to bind to the SARS-CoV-2 spike protein and prevent cell entry.
The simulations also predicted that the fat-soluble vitamins D, K, and A bind to the spike in the same way making the spike less able to infect cells.
Dr Deborah Shoemark, Senior Research Associate (Biomolecular Modelling) in the School of Biochemistry, who modelled the spike, said: “Our findings help explain how some vitamins may play a more direct role in combating COVID than their conventional support of the human immune system.
“Obesity is a major risk factor for severe COVID. Vitamin D is fat soluble and tends to accumulate in fatty tissue. This can lower the amount of Vitamin D available to obese individuals. Countries in which some of these vitamin deficiencies are more common have also suffered badly during the course of the pandemic. Our research suggests that some essential vitamins and fatty acids including linoleic acid may contribute to impeding the spike/ACE2 interaction. Deficiency in any one of them may make it easier for the virus to infect.”
The team’s simulations have also indicated that cholesterol could bind but may instead have a destabilising effect on the spike’s locked conformation, and favour the open, more infective conformation.
Dr Shoemark commented: “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 de-stabilises the “benign”, closed conformation or not, our results suggest that by directly interacting with the spike, the virus could sequester cholesterol to achieve the local concentrations required to facilitate cell entry and this may also account for the observed loss of circulating cholesterol post-infection.”
Professor Adrian Mulholland, of Bristol’s School of Chemistry, added: “Our simulations show how some molecules binding at the linoleic acid site affect the spike’s dynamics and lock it closed. They also show that drugs and vitamins active against the virus may work in the same way. Targeting this site may be a route to new anti-viral drugs. A next step would be to look at effects of dietary supplements and test viral replication in cells.”
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