Scavenger receptors in good cholesterol may allow SARS-CoV-2 into the human body, a study says

The structure and cross-sectional view of the human Coronavirus. Exhibition depicting the shape of the coronavirus and the cross-sectional view. The image shows the main elements including Spike S protein, HE protein, viral envelope and helical RNA. Image credit: Wikipedia

High-density lipoprotein (HDL) is a type of cholesterol that has a reputation for being good for you. As the United States Centers for Disease Control and Prevention (CDC) explains, while low-density lipoproteins (LDL or bad cholesterol) make up for most of the cholesterol in your body, it is HDL that absorbs it from all over the your system and carries it back to the liver. The liver then eliminates the LDL cholesterol and the HDL goes back to work.

Most studies indicate that high levels of HDL in the body can reduce the risks of heart disease and stroke. However, a new study published in the journal Metabolism of nature suggests that the SARS-CoV-2 virus, which causes COVID-19 infection, uses the body’s cholesterol synthesis system to enter host cells. The study, conducted by researchers from the Academy of Military Medical Sciences in China, shows that SARS-CoV-2 actually hijacks the essentially healthy process through which HDL works to gain entry into the body.

How SARS-CoV-2 drags on HDL synthesis

The connection between cholesterol and COVID-19 it is one that has been established for some time; this is reflected in the fact that studies, and even the CDC, list high cholesterol levels as a risk factor for severe COVID-19 pathology. A study published in Trends in anesthesia and intensive care in September 2020 explains that SARS-CoV-2 has ribonucleic acid (RNA) in its genetic material with a lipid envelope. Hence, the cholesterol synthesis pathways play an important role in the assembly, replication and infectivity of SARS-CoV-2 viral RNA in each case.

This could also be why this study and others have suggested that cholesterol-lowering drugs such as statins that reduce cholesterol synthesis and absorption also have antiviral effects and can be prescribed to COVID-19 patients to reduce severe outcomes. The new studio in Metabolism of nature expands this role of lipids in COVID-19 infection explaining the role played by the HDL B type 1 scavenger receptor (SR-B1).

HDL, scavenger receptors and COVID-19

The study explains that the angiotensin converting enzyme 2 (ACE2) receptor binds to the SARS-CoV-2 virus through a receptor binding domain. This binding is a complex mechanism, and research indicates that SARS-CoV-2 could also use other receptors in the host’s body to gain entry into cells. SR-B1, the researchers suggest, is one of these crucial co-receptors for SARS-CoV-2.

SR-B1 is a cell-surface HDL receptor that helps select bad cholesterol and other similar components in cells, which is a crucial cellular mechanism in the body. SR-B1 expression has been recognized in all cell types in the body, including adrenal, ovarian and testicular cells. SR-B1 is also responsible for the synthesis of vitamin E in the body, which is an essential micronutrient.

The researchers looked for cholesterol-regulated models in the SARS-CoV-2 virus and then evaluated the virus’s ability to bind to the host’s cholesterol. They found that certain components of the virus spike proteins quickly binded to cholesterol and successfully interacted with HDL and its components via SR-B1. This evaluation showed scientists that SARS-CoV-2 has specific affinities for host cholesterol and possibly HDL components as well.

Further investigation showed that HDL actually improved the SARS-CoV-2 protein activity in a dose-dependent manner and significantly increased viral entry and replication. Hence, HDL actually mediates the entry of SARS-CoV-2 into the human body. On the other hand, the researchers found that HDL cholesterol depletion in cell membranes inhibits SARS-CoV-2 infection, ultimately suggesting that further research on blocking SR-B1 and other sensitive HDL components could potentially provide avenues to treat and prevent COVID-19 infection.

For more information, read our article on high cholesterol.

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