SARS-CoV-2 requires cholesterol to invade cells and form mega cells.


Researchers engineered cells to carry proteins (green) from SARS-CoV-2 or its human target ACE2 (magenta). When the cells are near each other, the membranes of the cells fuse. Researchers believe a similar process allows the virus to slide into cells. Credit: d. Sanders et al. BioRxiv.org

People taking cholesterol-lowering drugs may be better than others at catching novel coronoviruses. A new study indicates that: The virus relies on the fatty molecule to acquire the cell’s protective membrane.

To cause COVID-19, the SARS-CoV-2 virus must make its way into people’s cells – and it requires a partner. Cholesterol, a waxy compound known for waxy compounding arteries, helps the virus open cells and slide inside, lab reports from Howard Hughes Medical Institute Investigator Clifford Brongwin.

Without cholesterol, the virus cannot eliminate the protective inhibition of a cell and cause infection, the team writes in an impression posted on BioRxiv.org on December 14, 2020. The work, which has recreated the initial phase of infection in laboratory-developed cells, has yet to undergo a peer-reviewed scientific vetting process.

Brangwyn, a biophysical engineer at Princeton University, says, “Cholesterol is an integral part of the membrane that surrounds cells and some viruses, including SARS-CoV-2. It is understandable that this is too much for infection is important.”

They say the discovery could see better health outcomes in patients with COVID-19, who know cholesterol-lowering drugs as statins. Although scientists have not yet accounted for the mechanism, this study and another published final decline suggest that drugs prevent SARS-CoV-2 from entering cells by denying cholesterol.

Brangwynne says that this discovery of the importance of cholesterol may help scientists develop new stopgap measures to treat COVID-19. A strange feature of the disease can also be highlighted: the formation of giant, mixed cells in the lungs of COVID-19 patients. In their experiments, scientists observed that similar mega cells emerge under the microscope.







The formation of mega cells (green) or syncytia found in the lungs of COVID-19 patients may cause many cells to fuse simultaneously. Credit: d. Sanders et al. BioRxiv.org

Mimicking a viral infection

In normal times, Brangwynne’s team studies the physical forces that organize molecules within cells. But in the spring of 2020, his laboratory, like many others around the world, focused on SARS-COV-2, training his biological expertise. They started investigating how viral and human proteins interact, and how this interaction enters SARS-CoV-2 cells. “We’re not a virology lab, we’ve never worked in this location before, so we’ve started thinking about the tools and approaches we’ve developed that we can use,” he says.

Brangwynne’s laboratory often works with laboratory-grown cells. To mimic SARS-CoV-2 infection, his team engineered such cells to sport one of two molecules, either the viral “spike protein” or the human ACE2 protein. (To cause infection, the virus must attach its membrane to a cell’s membrane. This process begins when spike proteins meet their cellular target, ACE2.)

In the laboratory, researchers viewed these cells as having evolved in the laboratory with these proteins. First, small tentacles originated from cells with ACE2 and clung to spike proteins on nearby cells. At these points, two unicellular membranes are connected and open, allowing the cells’ contents to be mixed. Eventually, the two cells melt together – scientists expect how the virus merges with one cell to infect it.

Researchers, including Princeton’s David Sanders, Chanelle Jumper and Paul Ackerman, tried to hinder the cell from melting. Using an automated system, he tested the effects of about 6,000 compounds, plus more than 30 tweaks to the spike protein. These experiments and others suggested that if there is a cholesterol deficiency in the membrane of SARS-CoV-2, the virus cannot enter its target cell.

This is not the first evidence showing cholesterol. A previous study by a group at the University of California, San Diego found that the body’s immune response to the virus produces a compound that lowers cholesterol – but in this case from the cell’s own membrane, not that of the virus.






Sincerely: Howard Hughes Medical Institute

“Cholesterol has been very well studied as a major factor in viral infections,” says Peter Casson, a University of Virginia scientist who studies the physical mechanisms of viral disease. “Interestingly, the role of cholesterol in viral entry varies greatly among viruses.” It is unclear how cholesterol aids SARS-CoV-2, but understanding that process may provide clues about the biology of the infection, says Kasen, who was not involved in the research.

The apparent beneficial effect of statins also extends to other viral infections. Some research suggests that these drugs worsen influenza virus by depriving them of cholesterol, says Kessen. But this may not be the only way that drugs can change the course of viral infections, he says. “This is a bit complicated because statins also modulate the immune response.”

Mysterious Mega Sale

As Brangwen’s experiments progressed, his team found something strange. The cells continued to attach to each other, spreading their contents together like eggs burst into a bowl. Compound cells, known as synthesia, which appear under the microscope, are found in healthy tissues, such as in the muscle and placenta, and in some viral diseases.

“People already knew that the COVID-19 virus would cause syncytia, but researchers were able to see the process beautifully,” says Jennifer Lippincott-Schwartz, a senior group leader at HHMI’s Genelia Research Campus. “Cell-cell fusion is itself a very under-studied field in biology.”

She describes how mega cells are found in the lungs of patients. “The formation of syncetia can be very harmful in the case of COVID, where it can destroy lung tissue and lead to death.”

Brangwynne states that it is not yet clear whether synchrotia play a major role in the progression of COVID-19. But, his team writes, the discovery of the contribution of cholesterol can help scientists fight the disease. “Our findings underscore the potential utility of statins and others [similar] the treatment. ”


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more information:
David W. Sanders et al. SARS-CoV-2 requires cholesterol for viral entry and pathological syncytia formation. Biorxiv (2020). DOI: 10.1101 / 2020.12.14.422737

Provided by Howard Hughes Medical Institute

Quotes: SARS-CoV-2 requires cholesterol to invade cells and mega cells (2021, 22 January), https://phys.org/news/2021-01-sars-cov-cholesterol, 22 January 2021 Retrieved from -invade-cells-. Mega. html

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