Fat-soluble vitamins may help reduce COVID-19 infectivity, proposes investigation

29 Jan 2021 --- Vitamins A, D and K, as well as antiviral drugs, may bind to SARS‐CoV‐2’s viral spike protein and thus reduce infectivity. In contrast, cholesterol may increase infectivity, which could explain why having high cholesterol is considered a risk factor for serious disease.

This is according to a computational investigation from the University of Bristol, UK, which used docking and molecular dynamic simulations to examine linoleate (an essential fatty acid) and other ligands.

Lead study author Dr. Deborah Shoemark believes that linoleate molecules’ presence in the closed conformation of the SARS-CoV-2 spike protein makes it harder for the virus to extend the spike receptor-binding domain to the ACE2 protein, which is thought to be the entry receptor for SARS‐CoV‐2. 

“We surmised [the viral spike protein] might provide a good potentially ‘druggable’ site and set about performing computer-based docking studies of approved drugs to this site to predict if and how well anything may fit,” she tells NutritionInsight. The researchers hope to prevent human cells becoming infected by preventing the viral spike protein from opening enough to interact with ACE2.

Fat-soluble vitamins show promise
While the linoleate was found to be a good binder, the fat-soluble vitamins K, D and A scored even higher, surprising the researchers.

“This was particularly interesting as deficiencies in vitamins D and K are associated with increased risk for severe COVID-19, and vitamin K deficiency predicts for mortality in hospitalized patients.”

Overall, steroids (including dexamethasone and vitamin D), retinoids (some known to be active in vitro and vitamin A) and vitamin K were identified as potential ligands that may stabilize the closed conformation.

“Our findings help explain how some vitamins may play a more direct role in combating COVID-19 than their conventional support of the human immune system,” says Shoemark.

Obesity and vitamin D
Prior investigations have found that individuals with obesity are more likely to suffer from more extreme effects of COVID-19. This investigation could point to some reasons for this phenomenon. 

Shoemark explains that vitamin D is fat-soluble and tends to accumulate in fatty tissue. This can lower the amount of vitamin D available to obese individuals, which could then have a knock-on effect on disease outcomes. 

Countries in which some of these vitamin deficiencies are more common have also suffered badly during the course of the pandemic, she notes.

“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 simulations showed how molecules binding at the linoleic acid site affect the spike’s dynamics and lock it closed.

Cholesterol impacts
Additionally, pre-existing high cholesterol levels have been associated with increased risk for severe COVID-19. 

Reports that the SARS-CoV-2 spike protein binds cholesterol led the team to investigate whether it could bind at the fatty acid binding site. 

Their simulations indicate that it could bind but that it may have a destabilizing effect on the spike’s locked conformation and favor the open, more infective conformation.

“We know that the use of cholesterol-lowering statins reduces the risk of developing severe COVID-19 and shortens recovery time in less severe cases,” says Shoemark. 

“Whether cholesterol destabilizes 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. This may also account for the observed loss of circulating cholesterol post-infection.”

Impacting recommendations? 
Addressing potential impacts for official recommendations, Shoemark states that vitamin D supplementation could be a good idea for those who are overweight, have darker skin tone or find it difficult to expose bare skin to sunshine. 

This is broadly in line with England’s recommendations. The country is supplying free vitamin D supplements this winter to people deemed vulnerable to COVID-19. 

“It can also do no harm to make sure the diet includes linoleate-containing oils, like sunflower oil. [Diets can also include] carrots or dairy for vitamin A, and a serving of spinach, kale, cabbage, broccoli, sprouts or other vitamin K-rich vegetables every day,” says Shoemark. 

Jonathan Ball, professor of molecular virology at the University of Nottingham, UK, and who was not involved with this study, warns that there is still “a lot of work to do” to show that lead chemicals work in the clinic and can effectively treat patients.

“In these worrying times of quack remedies and snake oil salesmen, it’s really important to understand that this study, and others like it, have identified interventions that might have an effect, but this needs to be proven through laboratory and human experimentation,” he emphasizes. 

By Katherine Durrell