November 26, 2020

expert reaction to study looking at SARS-CoV-2 and the cell’s internal cholesterol mechanisms

A study published in Nature Metabolism looks at how the cell’s internal cholesterol mechanisms facilitate SARS-CoV-2 entry.

Professor David Leake, Institute of Cardiovascular and Metabolic Health Research, University of Reading, said:

“This is an interesting and entirely novel paper, with good data, showing that the COVID-19 virus uses the cell-surface protein SR-BI to help it get into cells, although the main means of entry is by the protein ACE2. SR-B1 normally binds HDL (’good cholesterol’) to transfer cholesterol between the cell and this lipoprotein. The authors show that the S protein of the virus binds to cholesterol in HDL and HDL might act as a bridge between the virus particle and SR-B1. SR-B1 seems to help the virus to find its main receptor ACE2. Interestingly, an inhibitor of SR-B1 prevented the increased uptake of the virus.

“The authors show that SR-B1 is present in the lower respiratory tract, which is of course the main site in the body where serious COVID-19 complications arise.

“HDL is often considered to be protective against cardiovascular disease (although this is controversial), but it might have a potentially harmful effect in COVID-19 infections. People with diabetes or cardiovascular disease usually have lower, rather than increased, concentrations of HDL in their plasma and so this would not explain why they are at increased risk of serious complications from COVID-19. They are probably at higher risk of COVID-19 due to other factors.

“Targeting HDL to reduce its concentration in plasma as a therapy would be difficult. SR-B1 could be a target, as the authors suggest, but this might also be difficult as it fulfils useful functions in the body and reducing its levels on cells would not fully prevent virus entry into cells.”

Dr Riyaz Patel, Professor of Cardiology, UCL, said:

“The study explores how the virus enters the body’s cells, concluding that a particular receptor involved with cholesterol handling (SR-B1) makes it easier for the virus to do so.  Furthermore, this process works better in the presence of High Density Lipoprotein Cholesterol (HDL-C; also knowns as “good cholesterol”) particles.

“This is interesting as it adds more information about how the virus works to infect cells and may offer new treatment options. However the findings need to be replicated by others and more work is needed to understand the pathway in more detail.

“The press release says ‘This finding may help explain why individuals with both COVID-19 and a metabolic disorder such as diabetes or cardiovascular disease have elevated rates of morbidity and mortality‘, but I do not think this is accurate as the experiments only indicate that HDL-C (good cholesterol) particles may be relevant at the molecular level for the virus to infect cells and not whether having high or low blood levels of HDL cholesterol are relevant. Moreover, we know that people with diabetes, heart disease and those from BAME backgrounds who are at higher risk from COVID, often have low levels of HDL-C, so there is no obvious link. Similarly those with high HDL-C levels need not be alarmed either, as there is nothing to suggest they are at higher risk from COVID. If anything, factors that increase HDL-C (such as regular exercise) are much more important in protecting against ill health in general.”

‘HDL-scavenger receptor B type 1 facilitates SARS-CoV-2 entry’ by Wei et al is published in Nature Metabolism.

DOI: 10.1038/s42255-020-00324-0

All our previous output on this subject can be seen at this weblink:

www.sciencemediacentre.org/tag/covid-19

Declared interests

Dr Riyaz Patel: “No conflicts of interest.”

None others received.