Fat-soluble vitamins may help reduce COVID-19 infectivity

The research suggested that vitamins A, D and K, as well as antiviral drugs, could potentially reduce infectivity by binding to SARS‐CoV‐2’s viral spike protein.

In contrast, the study found that cholesterol might increase infectivity, which could explain why having high cholesterol was considered a risk factor for serious disease.

Researchers at the University of Bristol used docking and molecular dynamic simulations to examine linoleate (an essential fatty acid) and other ligands.

The presence of linoleate molecules in the closed conformation of the SARS-CoV-2 spike protein made it more difficult for the virus to extend the spike receptor-binding domain to the ACE2 protein, which is believed to the entry receptor for SARS-CoV-2, explained lead study author Dr Deborah Shoemark.

“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 might fit,” Shoemark told NutritionInsight.

The researchers hoped to prevent human cells becoming infected by preventing the viral spike protein from opening enough to interact with ACE2.

Linoleate was found to be a good binder. However, the fat-soluble vitamins A, D and K had scored even higher, the researchers said.

“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 hospitalised patients,” she said.

The study identified steroids (including dexamethasone and vitamin D), retinoids (some known to be active in vitro and vitamin A) and vitamin K as potential ligands that had the potential to stabilise 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,” added Shoemark.

The study linked to findings in separate investigations that obese individuals were more likely to suffer from more extreme effects of COVID-19.

As vitamin D was fat-soluble and tended to accumulate in fatty tissue, this could lower the amount of vitamin D available to obese individuals, Shoemark said, which could affect disease outcomes.

“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 also investigated if SARS-CoV-2 could bind cholesterol at the fatty acid binding site. Its simulations indicated that it could bind although it might have a destabilising effect on the spike’s locked 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,” Shoemark said.

“Whether cholesterol destabilises 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.”

Researchers believed this could account for the observed loss of circulating cholesterol post-infection.

Following the study’s findings, researchers suggested vitamin D supplementation for the overweight, those with darker skin tone or for those who received little direct sunshine.

“|t can also do no harm to make sure the diet includes the linoleate-containing oils, like sunflower,” she added.

However, Jonathan Ball, professor of molecular virology at the University of Nottingham, who was not involved in the study, was quoted by NutritionInsight as saying that more such studies needed to be proven through laboratory and human experimentation.