Very interesting, according to the authors it’s “like velcro”.
> [Covid] primarily uses a protein called the angiotensin-converting enzyme 2 (ACE2) receptor to enter human cells. Lung cells have high levels of ACE2 receptors, which is why the COVID-19 virus often causes severe problems in this organ of infected people.
> Like ACE2, LRRC15 is a receptor for coronavirus, meaning the virus can bind to it. But unlike ACE2, LRRC15 does not support infection. It can, however, stick to the virus and immobilise it. In the process, it prevents other vulnerable cells from becoming infected.
> “We think it acts a bit like Velcro, molecular Velcro, in that it sticks to the spike of the virus and then pulls it away from the target cell types,” Dr Loo said.
> “Basically, the virus is coated in the other part of the Velcro, and while it's trying to get to the main receptor, it can get caught up in this mesh of LRRC15,” Mr Waller said.
Given then that this protein is synthesized by our body, and in people with less severe COVId more of this protein was found, and less in more severe cases, could mRNA injections be used to stimulate/ramp up production?
The approach mentioned in the article is a nasal spray which I suppose is easier to manufacture.
This then begs the question, could mRNA injections be used in place of traditional medication?
Probably no if the medication needs to be targeted at a specific region, yes?
Could it be that the complexity of the protein affects our capacity to produce medication for it?
Or is it that the means of administration is the main factor on how we select our approach?
With mRNA vaccines we get the cells to produce the protein. Does this imply that synthesis of the spike protein is difficult, or is it that administration is?
> With mRNA vaccines we get the cells to produce the protein. Does this imply that synthesis of the spike protein is difficult, or is it that administration is?
It's that the mechanism of production of spike (inside infected cells) parallels the mechanism of production of spike protein in a natural infection. This stimulates the immune response against spike without need for additional adjuvants.
> This then begs the question, could mRNA injections be used in place of traditional medication?
Not my specialty, but as you say targeting may be difficult. There are various lipid carriers that I believe can target certain cell types or tissues, but I don't know how well these work, and of course actually distributing them so that they will reach lung tissue is also a matter. And then how well would they work in already infected lung tissue versus just spraying the lungs with the protein?
As for the second segment. I only have more questions now. Could it be that requesting that the cells produce additional proteins of a particular kind "overloads" them or simply "asks too much" in a fashion similar to a virus?
That seems unlikely unless the administered medication is simply "too much". I wonder, is there a saturation point? ie a point where additional mRNA medication does not result in more cells producing the target protein? Seems likely.
Which then raises the question, if such a saturation point exists, then what is causing cells to explode due to virus replication? Is it that the viral particles can not escape the cell and thus they "use" pressure? If so, have we encountered a virus that "opens up" a cell without damaging it and eventually becomes parasitic to the host?
It's probably the case that when cells die prematurely, they leave traces for our immune system to trigger an issue, so not destroying the cell seems like a beneficial evolutionary advantage. Otoh, the additional code required for this is likely very "expensive".
I hope a virologist drops by and clarifies on this.
I'm not a virologist, and this is taxing to my memory, so it will be a bit more basic than you might prefer, and won't be as accurate.
> Could it be that requesting that the cells produce additional proteins of a particular kind "overloads" them or simply "asks too much" in a fashion similar to a virus?
It could be. I believe that most of the cells that express from the mRNA vaccine do indeed die (from the immune response against them). I'm not positive about this though. In general if a cell is preferentially producing protein from a particular mRNA it doesn't have to resources left to do what is expected of it (including cellular maintenance).
> then what is causing cells to explode due to virus replication?
https://bio.libretexts.org/Bookshelves/Introductory_and_Gene...
"During release, the newly-created viruses are released from the host cell, either by causing the cell to break apart, waiting for the cell to die, or by budding off through the cell membrane."
According to the video below it can be caused by crowding. I think it can also be caused by virus proteins, or an apoptotic response - programmed cell death done to hinder the viruses ability to replicate more infectious particles. Often enough the cell does not burst, but simply buds off new virus. This is still very detrimental because the cell isn't doing what it is supposed to do, instead having been hijacked to create new viruses.
> If so, have we encountered a virus that "opens up" a cell without damaging it and eventually becomes parasitic to the host?
What I'm going to say won't directly answer your question, but it will answer the question you would have had if you knew a bit more. You want to look up lytic versus lysogenic viral replication. A basic overview: https://www.khanacademy.org/science/high-school-biology/hs-h...
I’ve seen the spikes mentioned a lot. Are these mechanical descriptions of how the spikes operate dumbed down for the average person to understand? Im surprised we don’t hear more about biologically destroying the cells instead.
My background on this comes from a neuroscience course in gradschool. The idea is that molecules and proteins “bind” to receptors which cause a cascade of reactions. The binding depends on the shape of the proteins and receptors.
A bridge like protein is created by removing parts of the spike protein through the cascade. The bridge connects the virus and the cell, and folds into itself to cause the two cells to merge.
I am not sure why it is called spike but I’d guess it’s because it looks like tiny spikes on the virus.
So when what we do with mRNA vaccines is produce the mRNA that encodes this protein, and wrap it in lipids which allow it to enter the cells and the cells manufacture it.
Now, our cells don’t naturally produce the spike protein, so this triggers our immune system to build antibodies which bind onto the proteins and render them useless, or flags for certain parts of our immune system. This results in increased production of certain cells and proteins for this specific protein.
Our immune system has the capacity to create antibodies for and bind onto all sorts of different proteins. This is because it the immune system is allowed to recombine and order its DNA. In order to avoid wrecking havoc at our own body, the immune system passes through filters which filter out proteins that would bind to the naturally occurring proteins in our body.
Van der Waals force[1] is sort of midway between chemical and mechanical interaction. We think of proteins as crystals because that’s how we can image them, but really they’re sort of floppy things that can often change their shape dynamically in response to forces and then exert different forces because of that. This leads to all kinds of interesting feedback loops. The polarity of the water molecules they’re floating around in plays a role too.
> [Covid] primarily uses a protein called the angiotensin-converting enzyme 2 (ACE2) receptor to enter human cells. Lung cells have high levels of ACE2 receptors, which is why the COVID-19 virus often causes severe problems in this organ of infected people.
> Like ACE2, LRRC15 is a receptor for coronavirus, meaning the virus can bind to it. But unlike ACE2, LRRC15 does not support infection. It can, however, stick to the virus and immobilise it. In the process, it prevents other vulnerable cells from becoming infected.
> “We think it acts a bit like Velcro, molecular Velcro, in that it sticks to the spike of the virus and then pulls it away from the target cell types,” Dr Loo said.
> “Basically, the virus is coated in the other part of the Velcro, and while it's trying to get to the main receptor, it can get caught up in this mesh of LRRC15,” Mr Waller said.
Given then that this protein is synthesized by our body, and in people with less severe COVId more of this protein was found, and less in more severe cases, could mRNA injections be used to stimulate/ramp up production?
The approach mentioned in the article is a nasal spray which I suppose is easier to manufacture.
This then begs the question, could mRNA injections be used in place of traditional medication?
Probably no if the medication needs to be targeted at a specific region, yes?
Could it be that the complexity of the protein affects our capacity to produce medication for it?
Or is it that the means of administration is the main factor on how we select our approach?
With mRNA vaccines we get the cells to produce the protein. Does this imply that synthesis of the spike protein is difficult, or is it that administration is?