Posted on 01/22/2021 12:28:02 PM PST by Red Badger
Researchers engineered cells to carry either a protein (green) from SARS-CoV-2 or its human target ACE2 (magenta). When near each other, the cells’ membranes fused. Researchers think a similar process lets the virus slip into cells. Credit: D. Sanders et al./bioRxiv.org
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People taking cholesterol-lowering drugs may fare better than others if they catch the novel coronavirus. A new study hints at why: the virus relies on the fatty molecule to get past the cell's protective membrane.
To cause COVID-19, the SARS-CoV-2 virus must force its way into people's cells—and it needs an accomplice. Cholesterol, the waxy compound better known for clogging arteries, helps the virus open cells up and slip inside, Howard Hughes Medical Institute Investigator Clifford Brangwynne's lab reports.
Without cholesterol, the virus cannot sneak past a cell's protective barrier and cause infection, the team writes in a preprint posted to bioRxiv.org on December 14, 2020. The work, which recreated the early stage of infection in lab-grown cells, has not yet undergone the scientific vetting process of peer review.
"Cholesterol is an integral part of the membranes that surround cells and some viruses, including SARS-CoV-2. It makes sense that it should be so important for infection," says Brangwynne, a biophysical engineer at Princeton University.
The finding might underlie the better health outcomes seen in COVID-19 patients taking cholesterol-lowering drugs known as statins, he adds. Although scientists haven't yet established the mechanism responsible, this study and another published last fall suggest the drugs prevent SARS-CoV-2 from getting into cells by denying it cholesterol.
This discovery of cholesterol's importance could help scientists develop new stopgap measures to treat COVID-19 until most people are vaccinated, Brangwynne says. The work may also shed light on a strange feature of the disease: the formation of giant, compound cells found in the lungs of COVID-19 patients. In their experiments, the scientists saw similar mega cells emerge under the microscope.
VIDEO AT LINK.............................
Many cells can fuse together, producing mega cells (green), or syncytia, similar to those found in the lungs of COVID-19 patients. 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 lab, like many others across the world, shifted focus, training their biological expertise on SARS-CoV-2. They began investigating how viral and human proteins interact, and how that interaction lets SARS-CoV-2 enter cells. "We're not a virology lab, we've never worked in this space before, so we started thinking about the tools and approaches we have developed that we could use," he says.
Brangwynne's lab often works with lab-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 an infection, the virus must fuse its membrane to a cell's membrane. This process begins when spike proteins meet their cellular target, ACE2.)
In the lab, the researchers watched as lab-grown cells with these proteins interacted. First, tiny tentacles emerged from cells with ACE2 and stuck to spike proteins on nearby cells. At these points, the two cellular membranes fused and openings formed, letting the cells' contents mix. Eventually, the two cells melded together—similar to how scientists expect the virus merges with a cell to infect it.
The researchers, including Princeton's David Sanders, Chanelle Jumper, and Paul Ackerman, tried to disrupt this cell melding. Using an automated system, they tested the effects of about 6,000 compounds, as well as more than 30 tweaks to the spike protein. These experiments and others suggested that if SARS-CoV-2's membrane lacks cholesterol, the virus cannot enter its target cell.
This isn't the first evidence implicating cholesterol. The 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 depletes cholesterol—but in this case from the cell's own membrane, not the virus's.
Credit: Howard Hughes Medical Institute "Cholesterol has been very well studied as an important factor in a large number of viral infections," says Peter Kasson, a scientist at the University of Virginia who studies the physical mechanisms of viral disease. "The interesting thing is that cholesterol's role in viral entry varies a lot between viruses." It's not clear exactly how cholesterol aids SARS-CoV-2, but understanding that process could offer clues about the biology of infection, says Kasson, who was not involved in the research.
The apparent beneficial effect of statins extends to other viral infections, too. Some research suggests that these drugs impair the influenza virus by depriving it of cholesterol, Kasson says. But that may not be the only way the drugs can alter the course of viral infections, he says. "It's a little complicated because statins also modify the immune response."
Mysterious mega cells
As Brangwynne's experiments ran, his team noticed something strange. The cells continued to engulf one another, spilling their contents together like eggs cracked into a bowl. The compound cells, known as syncytia, that appeared under the microscope resemble those found in healthy tissues, such as muscle and the placenta, and in some viral diseases.
"People already knew that the COVID-19 virus will create syncytia, but the researchers were able to visualize the process beautifully," says Jennifer Lippincott-Schwartz, a senior group leader at HHMI's Janelia Research Campus, who was not involved in the research. "Cell-cell fusion is itself a really under-studied area in biology."
The experiments likely illustrate how mega cells found in patients' lungs form, she says. "The formation of syncytia can be very injurious in the case of COVID, where it can destroy lung tissues and lead to death."
Brangwynne says it's not clear yet whether or not syncytia play a major role in the progression of COVID-19. But, his team writes, the discovery of cholesterol's contribution could help scientists fight the disease. "Our findings underscore the potential utility of statins and other [similar] treatments."
There have already been studies showing that the anti-cholesterol drug fenofibrate reduces the Covid infection to the level of the common cold. If you were on that particular drug, stay on it! I dd.
I’ve been on Lipitor since early last year!............................
At least in this case statins may provide some benefit.
You want to reduce blood cholesterol go on a high fat medium protein low carb diet.
I looked that up when someone here brought it up. Has an added benefit in that it is not a statin (if I remember correctly)
I was going to ask about that. Wouldn’t a keto diet that converts to triglyceride metabolism lower blood cholesterol?
Statins Mame people. I have seen several older people go down hill fast after taking them. They were fine before they took them.
I am using the best cholesterol reducer on earth...daily treadmill exercise for 27-30 minutes to cover 1 mile on up-slope of 2 to 3 degrees. At age nearing 81, no health issues at all, no drugs needed, no pains or aches, and more energy than when I was 50 years old.
And there is evidence, contrary to very early beliefs, that ACE inhibitors offer protection from the virus adhering to the ACEs and not damaging lung cells.
I’ve been on fenobibrate for a number of years. I thinks a report should be made about how recent studies show that if you drink your own urine once a day for five days you will have permanent immunity. Release that at 9 am and by 5 pm half the country will be walking around with piss breath. Simple sheep.
Individuals with high BMI and LDL cholesterol are at increased risk of COVID-19
The role of high cholesterol in age-related COVID19 lethality.
If we lived in an era with rule of law I would live to see statin manufacturers broke like big tobacco. But we don’t.
Statins are particularly hard on women. Starting studies showed there was no benefit derived by women taking them. People need to look at the actual data instead of headlines.
Nobody wants a heart attack, so most people do as their told.
That is a keto diet.
Screw this stupid bug ! and all the fear porn associated with it!!
Give it up everybody you’re scare Tactics have failed !!!
and we know that this is just a flu!!!
So go away with all your stupid scare stories ! about this stupid flu !!!
a new variant !!! It’s going to get you for sure
a new there’s a new strain again. It’s really scary this time.
it’s going to rip you likb from limb
throw your cross off a cliff !
have you run over by a train !!!
and all sorts of horrible things!!
So just stay home and keep our in a corner like we tell you to!!
Oh and by the way wear a face diaper all the time like we tell you to!
OK you good little slaves now?
Akira Endo discovered statins
When asked if he would take statins answered ”The indigo dyer wears white pants”
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