First case of postmortem study in a patient vaccinated against SARS-CoV-2

[Nemo]

Quinine and quinoline derivatives delay brain destruction by prions.

Quinoline derivatives are therapeutic candidates for transmissible spongiform encephalopathies - PubMed

We previously reported that quinacrine inhibited the formation of an abnormal prion protein (PrPres), a key molecule in the pathogenesis of transmissible spongiform encephalopathy, or prion disease, in scrapie-infected neuroblastoma cells. To elucidate the structural aspects of its inhibiting...

pubmed.ncbi.nlm.nih.gov

 

[Nemo]

Excellent Nemo do the pills from India require a prescription?

JRK, no, the pills from India do not require a prescription.

There may be other good places but I know this place is reliable. You can get HCQ, ivermectin, azithromycin, maybe other Fleming protocol drugs:

Ivermectin Tablet for Sale in USA, UK, Canada and EU | Ziverdo Kit Store

Buy Ivermectin tablets in the USA, UK, Canada, Australia, and EU. This medicine plays an important role in maintaining the health of a person. We ship worldwide and deliver In just 10 to 20 days.

www.ziverdokit.store

 

[J.R.K]

JRK, no, the pills from India do not require a prescription.

There may be other good places but I know this place is reliable. You can get HCQ, ivermectin, azithromycin, maybe other Fleming protocol drugs:

Ivermectin Tablet for Sale in USA, UK, Canada and EU | Ziverdo Kit Store

Buy Ivermectin tablets in the USA, UK, Canada, Australia, and EU. This medicine plays an important role in maintaining the health of a person. We ship worldwide and deliver In just 10 to 20 days.

www.ziverdokit.store

Thank you so much Nemo!,These would help clear the spike protein but the antibodies will still be present within the vaccinated person, what outcome for these people awaits if they have cleared out the spike protein but the antibodies to the spike protein remain dormant within the lymph nodes when contact with either a spike protein via transmission or the wild version of the virus ?

 

[Nemo]

Thank you so much Nemo!,These would help clear the spike protein but the antibodies will still be present within the vaccinated person, what outcome for these people awaits if they have cleared out the spike protein but the antibodies to the spike protein remain dormant within the lymph nodes when contact with either a spike protein via transmission or the wild version of the virus ?

If the vax spike proteins are gone, I believe you will stop making the antibodies to them and your immune system will go back to normal from the vax "reprogramming". I'm not 100% sure, but that's pretty much the only reason they'd want to get the RNA into your DNA to make the spike proteins forever. So I'm confident but still trying to disprove that theory.

Obviously if the antibodies are gone, you don't have to worry about ADE or autoimmune attacks.

 

[Mito]

Methylene blue will work to keep you from bad Covid symptoms while your immune system clears the virus.

But I think if you're in a situation where you're constantly picking up spike proteins from vaxxed people, I would do ivermectin or HCQ.
You could do full prophylaxis weekly or just do a once a month or quarterly cleaning. I would pay attention to any symptoms you're getting and base your protocol on that. More people who are in constant contact with vaxxed people are telling me about flu-like symptoms, headaches, bad nosebleeds, brain fog and more. I would take those symptoms seriously.

The spike protein can't reproduce on its own. It needs the virus or vax RNA. You just have to worry about it binding to cells and causing inflammation, even blood clotting and worse effects if you pick up enough and your immune system isn't clearing it out.

Still looking for that study on which receptor fenbendazole stops the spike protein from binding to. It's not ACE2. I think duckduckgo is now censoring studies because I can't find a number of them that I saw as recently as two weeks ago.

“Methylene blue inhibited the entry of a SARS-CoV-2 spike bearing pseudovirus into ACE2-expressing cells with similar IC50 (3.5 μM).”

Methylene Blue Inhibits the SARS-CoV-2 Spike-ACE2 Protein-Protein Interaction-a Mechanism that can Contribute to its Antiviral Activity Against COVID-19 - PubMed

Due to our interest in the chemical space of organic dyes to identify potential small-molecule inhibitors (SMIs) for protein-protein interactions (PPIs), we initiated a screen of such compounds to assess their inhibitory activity against the interaction between SARS-CoV-2 spike protein and its...

pubmed.ncbi.nlm.nih.gov

“Emodin, an anthraquinone compound derived from genus Rheum and Polygonum, significantly blocked the S protein and ACE2 interaction in a dose-dependent manner. It also inhibited the infectivity of S protein-pseudotyped retrovirus to Vero E6 cells.”

Emodin blocks the SARS coronavirus spike protein and angiotensin-converting enzyme 2 interaction

Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused by a novel coronavirus (SARS-CoV). SARS-CoV spike (S) protein, a typ…

www.sciencedirect.com

 

[J.R.K]

“Methylene blue inhibited the entry of a SARS-CoV-2 spike bearing pseudovirus into ACE2-expressing cells with similar IC50 (3.5 μM).”

Methylene Blue Inhibits the SARS-CoV-2 Spike-ACE2 Protein-Protein Interaction-a Mechanism that can Contribute to its Antiviral Activity Against COVID-19 - PubMed

Due to our interest in the chemical space of organic dyes to identify potential small-molecule inhibitors (SMIs) for protein-protein interactions (PPIs), we initiated a screen of such compounds to assess their inhibitory activity against the interaction between SARS-CoV-2 spike protein and its...

pubmed.ncbi.nlm.nih.gov

“Emodin, an anthraquinone compound derived from genus Rheum and Polygonum, significantly blocked the S protein and ACE2 interaction in a dose-dependent manner. It also inhibited the infectivity of S protein-pseudotyped retrovirus to Vero E6 cells.”

Emodin blocks the SARS coronavirus spike protein and angiotensin-converting enzyme 2 interaction

Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused by a novel coronavirus (SARS-CoV). SARS-CoV spike (S) protein, a typ…

www.sciencedirect.com

So a little cascara segrada might help with the shedding or transmission aspects as well as Ivermectin and hydroxychloroquine I am wondering if vitamin K2 since it is also a quinone would be beneficial? Even tonic water although the quinones are at low levels if one were unable to get hydroxychloroquinone

 

[Peatness]

So a little cascara segrada might help with the shedding or transmission aspects as well as Ivermectin and hydroxychloroquine I am wondering if vitamin K2 since it is also a quinone would be beneficial? Even tonic water although the quinones are at low levels if one were unable to get hydroxychloroquinone

I had the same thought about vitamin K2 today. That would be great. Q10 is also recommended.

 

[J.R.K]

I had the same thought about vitamin K2 today. That would be great. Q10 is also recommended.

I presume that you mean CoQ 10. I always get confused as to which is the better one Ubiquinol or Ubiquinone or the one called Mito Q any help or thoughts would be appreciated.

 

[Peatness]

I presume that you mean CoQ 10. I always get confused as to which is the better one Ubiquinol or Ubiquinone or the one called Mito Q any help or thoughts would be appreciated.

Dr Peat favours ubiquinone. I am not sure the exact reason. I don't know anything about Mito Q

 

[J.R.K]

Dr Peat favours ubiquinone. I am not sure the exact reason. I don't know anything about Mito Q

Thank you @Pina

 

[Nemo]

Fleming's protection protocol for vaxxed people involves drugs that aren't readily available for most people, including to deal with vax-caused prion diseases. I'm worried vaxxed people will look at the list of transfusions and hard-to-get drugs and give up on protecting themselves.

So here's why I think a dose of ivermectin, followed by weekly hydroxychloroquine, in the doses Fleming recommends, will likely do the job of protecting most vaxxers from the prion disease vax side effects.

Prion diseases are caused by misfolding of important bodily proteins. When they misfold they form toxic molecules like tiny fibers that damage brain cells.

Prion diseases include Mad Cow and probably Alzheimer's, Parkinson's, and ALS. Reportedly we're pretty sure we've identified the toxic particles causing these diseases. We know Mad Cow and Lewy bodies are forming in the brains of macaques and humanized mice injected with the spike protein.

Susceptibility to misfolding depends on something called the "glycine zipper motif". That's a pattern of two glycine residues spaced by three intervening amino acids, represented as GxxxG. The prion that causes Mad Cow has ten of those zipper motifs in a row. Amyloid-β precursor protein (APP), which plays a central role in Alzheimer's, has four zipper motifs. These zipper motifs are common in transmembrane proteins.

The Bat Plague spike protein is a transmembrane protein that contains FIVE glycine zipper motifs. It was designed with those zipper motifs with extra proline in the x positions to keep it from fusing with the cell membrane, which makes it more susceptible to misfolding.

In other words, it looks like it's the spike protein itself that is designed to work as a prion. It also binds to many known endogenous proteins and may induce their misfolding into potential prions.

Either way, get rid of the spike proteins and you likely get rid of prion disease. Spike proteins that get into your brain bind to ACE2 receptors in your brain. Hydroxychloroquine easily crosses the blood brain barrier and, like ivermectin, has been proven to block binding of spike proteins to ACE2.

While the prion-domain on the tip of the spike protein sounds scary, the vax scientists I follow, plus one of the studies Fleming links to, have concluded it's stuck there merely to enhance binding with ACE2 receptors and facilitate the spike proteins' crossing of the blood brain barrier.

There are other potential triggers of misfolding in the vaxxes, like RNA fragments. And there are other places, like the gut, where misfolding can take place and then misfolded proteins will be transferred to the brain via the vagus nerve, probably in the form of exosomes. But that likely depends on an inflammatory state, and the spike proteins are highly inflammatory, while ivermectin and HCQ are anti-inflammatory and get rid of spike proteins.

There are other problems in the vaxxes, like cationic lipids that create an acidic pH and inflammation conducive to misfolding. And there are other receptors that the spike protein binds to. But a basically healthy vaxxed person who kicks the spike proteins off his ACE2s should be in a good position to clean up the rest of the mess on his own, especially when starting with a dose of ivermectin, which appears to restore part of your vax-disabled immune system.

One reason to be concerned about shedding is that prions that have traveled from one animal to another wind up in the lymph system, especially the spleen, another place where misfolded proteins accumulate and from which they are transferred via exosomes to the brain. Since the vax nanoparticles accumulate in the spleen, it seems likely spike proteins an unvaxxed person may pick up via shedding will too.

Now, if you look up studies on the effectiveness of hydroxychloroquine for prion diseases or Alzheimer's, you will learn it is completely ineffective. And related drugs like Mefloquine, which appear effective in vitro, have been shown not to adequately cross the blood brain barrier. But don't be discouraged by that. We're not dealing with natural prions or other causes of these diseases here. We're dealing with an injected bioweapon prion against which hydroxychloroquine is highly effective, including in the brain.

One final comment. You remember that Alzheimer's drug the FDA just approved after it was unanimously rejected by the FDA advisory board of big-time doctor scientists? Three of the advisors resigned from the board in protest. One has been telling the media it's the worst drug the FDA has ever approved.

To me it's obvious the FDA knows how the vax spike protein will act as a prion. But they're not approving this drug to help people through what's coming. This drug is another remdesivir, totally worthless but grotesquely expensive. Since they've managed to scare a huge chunk of the population off hydroxychloroquine, they probably figure they can make coin off this new piece of dung.

 

[J.R.K]

Fleming's protection protocol for vaxxed people involves drugs that aren't readily available for most people, including to deal with vax-caused prion diseases. I'm worried vaxxed people will look at the list of transfusions and hard-to-get drugs and give up on protecting themselves.

So here's why I think a dose of ivermectin, followed by weekly hydroxychloroquine, in the doses Fleming recommends, will likely do the job of protecting most vaxxers from the prion disease vax side effects.

Prion diseases are caused by misfolding of important bodily proteins. When they misfold they form toxic molecules like tiny fibers that damage brain cells.

Prion diseases include Mad Cow and probably Alzheimer's, Parkinson's, and ALS. Reportedly we're pretty sure we've identified the toxic particles causing these diseases. We know Mad Cow and Lewy bodies are forming in the brains of macaques and humanized mice injected with the spike protein.

Susceptibility to misfolding depends on something called the "glycine zipper motif". That's a pattern of two glycine residues spaced by three intervening amino acids, represented as GxxxG. The prion that causes Mad Cow has ten of those zipper motifs in a row. Amyloid-β precursor protein (APP), which plays a central role in Alzheimer's, has four zipper motifs. These zipper motifs are common in transmembrane proteins.

The Bat Plague spike protein is a transmembrane protein that contains FIVE glycine zipper motifs. It was designed with those zipper motifs with extra proline in the x positions to keep it from fusing with the cell membrane, which makes it more susceptible to misfolding.

In other words, it looks like it's the spike protein itself that is designed to work as a prion. It also binds to many known endogenous proteins and may induce their misfolding into potential prions.

Either way, get rid of the spike proteins and you likely get rid of prion disease. Spike proteins that get into your brain bind to ACE2 receptors in your brain. Hydroxychloroquine easily crosses the blood brain barrier and, like ivermectin, has been proven to block binding of spike proteins to ACE2.

While the prion-domain on the tip of the spike protein sounds scary, the vax scientists I follow, plus one of the studies Fleming links to, have concluded it's stuck there merely to enhance binding with ACE2 receptors and facilitate the spike proteins' crossing of the blood brain barrier.

There are other potential triggers of misfolding in the vaxxes, like RNA fragments. And there are other places, like the gut, where misfolding can take place and then misfolded proteins will be transferred to the brain via the vagus nerve, probably in the form of exosomes. But that likely depends on an inflammatory state, and the spike proteins are highly inflammatory, while ivermectin and HCQ are anti-inflammatory and get rid of spike proteins.

There are other problems in the vaxxes, like cationic lipids that create an acidic pH and inflammation conducive to misfolding. And there are other receptors that the spike protein binds to. But a basically healthy vaxxed person who kicks the spike proteins off his ACE2s should be in a good position to clean up the rest of the mess on his own, especially when starting with a dose of ivermectin, which appears to restore part of your vax-disabled immune system.

One reason to be concerned about shedding is that prions that have traveled from one animal to another wind up in the lymph system, especially the spleen, another place where misfolded proteins accumulate and from which they are transferred via exosomes to the brain. Since the vax nanoparticles accumulate in the spleen, it seems likely spike proteins an unvaxxed person may pick up via shedding will too.

Last, if you look up studies on the effectiveness of hydroxychloroquine for prion diseases or Alzheimer's, you will learn it is completely ineffective. And related drugs like Mefloquine, which appear effective in vitro, have been shown not to adequately cross the blood brain barrier. But don't be discouraged by that. We're not dealing with natural prions or other causes of these diseases here. We're dealing with an injected bioweapon prion against which hydroxychloroquine is highly effective, including in the brain

So it sounds like good preventative medicine for an unvaccinated person to use hydroxychloroquine and some Ivermectin as good preventative maintenance until the smoke clears if it does. Ivermectin once a week and hydroxychloroquine once a month as mentioned above just to clear the system, the irony of going into a lockdown mode being unnecessary for the virus but having to take preventative measures for the mandate of the vaccine is not lost on me.

 

[Nemo]

So it sounds like good preventative medicine for an unvaccinated person to use hydroxychloroquine and some Ivermectin as good preventative maintenance until the smoke clears if it does. Ivermectin once a week and hydroxychloroquine once a month as mentioned above just to clear the system, the irony of going into a lockdown mode being unnecessary for the virus but having to take preventative measures for the mandate of the vaccine is not lost on me.

JRK, hydroxychloroquine has a long half-life. Looks like it's roughly 18 days. Ivermectin is more like 18 hours if I remember correctly. But ivermectin restores part of your immune system that the vax spike protein "reprograms".

The way I'm handling this for my own family is I'd do 1-2 doses of 12 mg ivermectin, one day right after the other, to clear whatever is in you.

If you've got continuing exposure, I'd start the hydroxychloroquine protocol for weekly after that until the smoke clears. The hydroxychloroquine gives you good continuous coverage safely. You really can't do ivermectin frequently enough for that.

If you mostly have little exposure, but are worried about occasional exposure, you could possibly do the ivermectin dose occasionally, as needed.

 

[Nemo]

“Methylene blue inhibited the entry of a SARS-CoV-2 spike bearing pseudovirus into ACE2-expressing cells with similar IC50 (3.5 μM).”

Methylene Blue Inhibits the SARS-CoV-2 Spike-ACE2 Protein-Protein Interaction-a Mechanism that can Contribute to its Antiviral Activity Against COVID-19 - PubMed

Due to our interest in the chemical space of organic dyes to identify potential small-molecule inhibitors (SMIs) for protein-protein interactions (PPIs), we initiated a screen of such compounds to assess their inhibitory activity against the interaction between SARS-CoV-2 spike protein and its...

pubmed.ncbi.nlm.nih.gov

“Emodin, an anthraquinone compound derived from genus Rheum and Polygonum, significantly blocked the S protein and ACE2 interaction in a dose-dependent manner. It also inhibited the infectivity of S protein-pseudotyped retrovirus to Vero E6 cells.”

Emodin blocks the SARS coronavirus spike protein and angiotensin-converting enzyme 2 interaction

Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused by a novel coronavirus (SARS-CoV). SARS-CoV spike (S) protein, a typ…

www.sciencedirect.com

That is fantastic.

Thank you for posting this.

These are the first studies I've seen actually dealing with preventing spike binding.

 

[Nemo]

“Methylene blue inhibited the entry of a SARS-CoV-2 spike bearing pseudovirus into ACE2-expressing cells with similar IC50 (3.5 μM).”

Methylene Blue Inhibits the SARS-CoV-2 Spike-ACE2 Protein-Protein Interaction-a Mechanism that can Contribute to its Antiviral Activity Against COVID-19 - PubMed

Due to our interest in the chemical space of organic dyes to identify potential small-molecule inhibitors (SMIs) for protein-protein interactions (PPIs), we initiated a screen of such compounds to assess their inhibitory activity against the interaction between SARS-CoV-2 spike protein and its...

pubmed.ncbi.nlm.nih.gov

“Emodin, an anthraquinone compound derived from genus Rheum and Polygonum, significantly blocked the S protein and ACE2 interaction in a dose-dependent manner. It also inhibited the infectivity of S protein-pseudotyped retrovirus to Vero E6 cells.”

Emodin blocks the SARS coronavirus spike protein and angiotensin-converting enzyme 2 interaction

Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused by a novel coronavirus (SARS-CoV). SARS-CoV spike (S) protein, a typ…

www.sciencedirect.com

What dose are we telling people? I know Haidut's talked about 5 mg or something with MB, but what is the minimum dose you think would be effective for protection from routine shedding?

Do you think this would clear the spikes from people who got the shot?

 

[J.R.K]

JRK, hydroxychloroquine has a long half-life. Looks like it's roughly 18 days. Ivermectin is more like 18 hours if I remember correctly. But ivermectin restores part of your immune system that the vax spike protein "reprograms".

The way I'm handling this for my own family is I'd do 1-2 doses of 12 mg ivermectin, one day right after the other, to clear whatever is in you.

If you've got continuing exposure, I'd start the hydroxychloroquine protocol for weekly after that until the smoke clears. The hydroxychloroquine gives you good continuous coverage safely. You really can't do ivermectin frequently enough for that.

If you mostly have little exposure, but are worried about occasional exposure, you could possibly do the ivermectin dose occasionally, as needed.

Thank you Nemo, I suppose the one other thing that is helping as mentioned in this page is that I have been taking 1 mg per day methylene blue which will help provide protection somewhat until the hydroxychloroquine arrives.
It appears we have many things in the arsenal to help us I use niacinamide daily as well and Thiamine so they to will help I think on the inflammatory side of things as well as progesterone.

 

[Nemo]

Fleming's protection protocol for vaxxed people involves drugs that aren't readily available for most people, including to deal with vax-caused prion diseases. I'm worried vaxxed people will look at the list of transfusions and hard-to-get drugs and give up on protecting themselves.

So here's why I think a dose of ivermectin, followed by weekly hydroxychloroquine, in the doses Fleming recommends, will likely do the job of protecting most vaxxers from the prion disease vax side effects.

Prion diseases are caused by misfolding of important bodily proteins. When they misfold they form toxic molecules like tiny fibers that damage brain cells.

Prion diseases include Mad Cow and probably Alzheimer's, Parkinson's, and ALS. Reportedly we're pretty sure we've identified the toxic particles causing these diseases. We know Mad Cow and Lewy bodies are forming in the brains of macaques and humanized mice injected with the spike protein.

Susceptibility to misfolding depends on something called the "glycine zipper motif". That's a pattern of two glycine residues spaced by three intervening amino acids, represented as GxxxG. The prion that causes Mad Cow has ten of those zipper motifs in a row. Amyloid-β precursor protein (APP), which plays a central role in Alzheimer's, has four zipper motifs. These zipper motifs are common in transmembrane proteins.

The Bat Plague spike protein is a transmembrane protein that contains FIVE glycine zipper motifs. It was designed with those zipper motifs with extra proline in the x positions to keep it from fusing with the cell membrane, which makes it more susceptible to misfolding.

In other words, it looks like it's the spike protein itself that is designed to work as a prion. It also binds to many known endogenous proteins and may induce their misfolding into potential prions.

Either way, get rid of the spike proteins and you likely get rid of prion disease. Spike proteins that get into your brain bind to ACE2 receptors in your brain. Hydroxychloroquine easily crosses the blood brain barrier and, like ivermectin, has been proven to block binding of spike proteins to ACE2.

While the prion-domain on the tip of the spike protein sounds scary, the vax scientists I follow, plus one of the studies Fleming links to, have concluded it's stuck there merely to enhance binding with ACE2 receptors and facilitate the spike proteins' crossing of the blood brain barrier.

There are other potential triggers of misfolding in the vaxxes, like RNA fragments. And there are other places, like the gut, where misfolding can take place and then misfolded proteins will be transferred to the brain via the vagus nerve, probably in the form of exosomes. But that likely depends on an inflammatory state, and the spike proteins are highly inflammatory, while ivermectin and HCQ are anti-inflammatory and get rid of spike proteins.

There are other problems in the vaxxes, like cationic lipids that create an acidic pH and inflammation conducive to misfolding. And there are other receptors that the spike protein binds to. But a basically healthy vaxxed person who kicks the spike proteins off his ACE2s should be in a good position to clean up the rest of the mess on his own, especially when starting with a dose of ivermectin, which appears to restore part of your vax-disabled immune system.

One reason to be concerned about shedding is that prions that have traveled from one animal to another wind up in the lymph system, especially the spleen, another place where misfolded proteins accumulate and from which they are transferred via exosomes to the brain. Since the vax nanoparticles accumulate in the spleen, it seems likely spike proteins an unvaxxed person may pick up via shedding will too.

Now, if you look up studies on the effectiveness of hydroxychloroquine for prion diseases or Alzheimer's, you will learn it is completely ineffective. And related drugs like Mefloquine, which appear effective in vitro, have been shown not to adequately cross the blood brain barrier. But don't be discouraged by that. We're not dealing with natural prions or other causes of these diseases here. We're dealing with an injected bioweapon prion against which hydroxychloroquine is highly effective, including in the brain.

One final comment. You remember that Alzheimer's drug the FDA just approved after it was unanimously rejected by the FDA advisory board of big-time doctor scientists? Three of the advisors resigned from the board in protest. One has been telling the media it's the worst drug the FDA has ever approved.

To me it's obvious the FDA knows how the vax spike protein will act as a prion. But they're not approving this drug to help people through what's coming. This drug is another remdesivir, totally worthless but grotesquely expensive. Since they've managed to scare a huge chunk of the population off hydroxychloroquine, they probably figure they can make coin off this new piece of dung.

Here's a doctor talking about the misfolding proteins, the way the spike protein is configured not to fuse with the membrane, increasing the risk of misfolding, etc.

She's talking about early-onset Parkinson's. The studies Fleming links to show prion diseases/Lewy bodies 18 months to 2 years after exposure:


View: https://twitter.com/heidegger79/status/1404048666311135237

 

[md_a]

Two important methods as prevention / treatment against `covid` is to block the virus / Spike protein from attaching to ACE2 and to reduce the the angiotensin II type 1 receptor (AT1 receptor)
..........

The mechanistic overview of SARS-CoV-2 using angiotensin-converting enzyme 2 to enter the cell for replication: possible treatment options related to the renin–angiotensin system​

Abstract​

The SARS-CoV-2 pandemic is a healthcare crisis caused by insufficient knowledge applicable to effectively combat the virus. Therefore, different scientific discovery strategies need to be connected, to generate a rational treatment which can be made available as rapidly as possible. This relies on a solid theoretical understanding of the mechanisms of SARS-CoV-2 infection and host responses, which is coupled to the practical experience of clinicians that are treating patients. Because SARS-CoV-2 enters the cell by binding to angiotensin-converting enzyme 2 (ACE2), targeting ACE2 to prevent such binding seems an obvious strategy to combat infection. However, ACE2 performs its functions outside the cell and was found to enter the cell only by angiotensin II type 1 receptor (AT1R)-induced endocytosis, after which ACE2 is destroyed. This means that preventing uptake of ACE2 into the cell by blocking AT1R would be a more logical approach to limit entry of SARS-CoV-2 into the cell. Since ACE2 plays an important protective role in maintaining key biological processes, treatments should not disrupt the functional capacity of ACE2, to counterbalance the negative effects of the infection. Based on known mechanisms and knowledge of the characteristics of SARS-CoV we propose the hypothesis that the immune system facilitates SARS-CoV-2 replication which disrupts immune regulatory mechanisms. The proposed mechanism by which SARS-CoV-2 causes disease immediately suggests a possible treatment, since the AT1R is a key player in this whole process. AT1R antagonists appear to be the ideal candidate for the treatment of SARS-CoV-2 infection. AT1R antagonists counterbalance the negative consequences of angiotesnin II and, in addition, they might even be involved in preventing the cellular uptake of the virus without interfering with ACE2 function. AT1R antagonists are widely available, cheap, and safe. Therefore, we propose to consider using AT1R antagonists in the treatment of SARS-CoV-2.

Conclusion​

Because SARS-CoV-2 enters the cell bound to ACE2, which induces ACE2 deficiency at the cell membrane, AngII is persistently activated. Increased AngII induces activation of AT1R, causing more uptake of SARS-CoV-2 and increasing ACE2 deficiency, thus maintaining and exacerbating a non-specific immune response, consisting of cytokine-induced inflammation. This non-specific immune response is an attempt to reduce the viral load, while the specific immune response is mounted. Unrestrained AngII eventually causes death by respiratory distress induced by excessive inflammation and its deleterious effects on other organs. Therefore, SARS-CoV-2-induced mortality is promoted by three mechanisms: (i) increased AngII induces endocytosis of ACE2-bound SARS-CoV-2, leading to ACE2 deficiency and viral replication; (ii) ACE2 deficiency prevents the priming of an adaptive immune response by lack of NO; and (iii) Ang II induces an increase in viral load leading to an increased innate immune response and a further increase in AngII levels. Therefore, treatments should aim at preventing the AngII ‘storm’ in an early phase of the infection, restoring the modulation of NO, and preventing the entry of SARS-CoV-2 into the cell. All these mechanisms are targeted by AT1R antagonists. They may reduce morbid inflammatory distress and provide an environment to facilitate an effective, virus-specific adaptive immune response.

The mechanistic overview of SARS-CoV-2 using angiotensin-converting enzyme 2 to enter the cell for replication: possible treatment options related to the renin–angiotensin system

..........

Emodin blocks the SARS coronavirus spike protein and angiotensin-converting enzyme 2 interaction​

Abstract​

Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused by a novel coronavirus (SARS-CoV). SARS-CoV spike (S) protein, a type I membrane-bound protein, is essential for the viral attachment to the host cell receptor angiotensin-converting enzyme 2 (ACE2). By screening 312 controlled Chinese medicinal herbs supervised by Committee on Chinese Medicine and Pharmacy at Taiwan, we identified that three widely used Chinese medicinal herbs of the family Polygonaceae inhibited the interaction of SARS-CoV S protein and ACE2. The IC(50) values for Radix et Rhizoma Rhei (the root tubers of Rheum officinale Baill.), Radix Polygoni multiflori (the root tubers of Polygonum multiflorum Thunb.), and Caulis Polygoni multiflori (the vines of P. multiflorum Thunb.) ranged from 1 to 10 microg/ml. Emodin, an anthraquinone compound derived from genus Rheum and Polygonum, significantly blocked the S protein and ACE2 interaction in a dose-dependent manner. It also inhibited the infectivity of S protein-pseudotyped retrovirus to Vero E6 cells. These findings suggested that emodin may be considered as a potential lead therapeutic agent in the treatment of SARS.

Emodin blocks the SARS coronavirus spike protein and angiotensin-converting enzyme 2 interaction - PubMed

.......

SARS-CoV-2 spike protein promotes IL-6 trans-signaling by activation of angiotensin II receptor signaling in epithelial cells​

Abstract​

Cytokine storm is suggested as one of the major pathological characteristics of SARS-CoV-2 infection, although the mechanism for initiation of a hyper-inflammatory response, and multi-organ damage from viral infection is poorly understood. In this virus-cell interaction study, we observed that SARS-CoV-2 infection or viral spike protein expression alone inhibited angiotensin converting enzyme-2 (ACE2) receptor protein expression. The spike protein promoted an angiotensin II type 1 receptor (AT1) mediated signaling cascade, induced the transcriptional regulatory molecules NF-κB and AP-1/c-Fos via MAPK activation, and increased IL-6 release. SARS-CoV-2 infected patient sera contained elevated levels of IL-6 and soluble IL-6R. Up-regulated AT1 receptor signaling also influenced the release of extracellular soluble IL-6R by the induction of the ADAM-17 protease. Use of the AT1 receptor antagonist, Candesartan cilexetil, resulted in down-regulation of IL-6/soluble IL-6R release in spike expressing cells. Phosphorylation of STAT3 at the Tyr705 residue plays an important role as a transcriptional inducer for SOCS3 and MCP-1 expression. Further study indicated that inhibition of STAT3 Tyr705 phosphorylation in SARS-CoV-2 infected and viral spike protein expressing epithelial cells did not induce SOCS3 and MCP-1 expression. Introduction of culture supernatant from SARS-CoV-2 spike expressing cells on a model human liver endothelial Cell line (TMNK-1), where transmembrane IL-6R is poorly expressed, resulted in the induction of STAT3 Tyr705 phosphorylation as well as MCP-1 expression. In conclusion, our results indicated that the presence of SARS-CoV-2 spike protein in epithelial cells promotes IL-6 trans-signaling by activation of the AT1 axis to initiate coordination of a hyper-inflammatory response.

SARS-CoV-2 spike protein promotes IL-6 trans-signaling by activation of angiotensin II receptor signaling in epithelial cells - PubMed

Cytokine storm is suggested as one of the major pathological characteristics of SARS-CoV-2 infection, although the mechanism for initiation of a hyper-inflammatory response, and multi-organ damage from viral infection is poorly understood. In this virus-cell interaction study, we observed that...

pubmed.ncbi.nlm.nih.gov

 

[J.R.K]

Thanks for this @md_a! I haven’t spoken to you in a while but you have always got such great finds. I for one appreciate the help in understanding.
So what I am getting from this (and please do correct if I am wrong as an expert on this I am not by any stretch of the imagination this is what I feel I am contributing to the forum the average guy who knows very little but is not afraid to ask questions)
Cascara segrada would provide a source of emotion which would help prevent the spike proteins spread via transmission bind to the ACE2 receptor and perhaps detox (for lack of a better term) it from our system or at least help move it on the ejection side of things?
Is there a reference to possibly the pine needle tea mentioned earlier in another thread the word polygonaceae seems familiar but I could be wrong.

 

[Nemo]

Thanks for this @md_a! I haven’t spoken to you in a while but you have always got such great finds. I for one appreciate the help in understanding.
So what I am getting from this (and please do correct if I am wrong as an expert on this I am not by any stretch of the imagination this is what I feel I am contributing to the forum the average guy who knows very little but is not afraid to ask questions)
Cascara segrada would provide a source of emotion which would help prevent the spike proteins spread via transmission bind to the ACE2 receptor and perhaps detox (for lack of a better term) it from our system or at least help move it on the ejection side of things?
Is there a reference to possibly the pine needle tea mentioned earlier in another thread the word polygonaceae seems familiar but I could be wrong.

Dandelion tea works too, even for variants:

Common dandelion (Taraxacum officinale) efficiently blocks the interaction between ACE2 cell surface receptor and SARS-CoV-2 spike protein D614, mutants D614G, N501Y, K417N and E484K in vitro

On 11th March 2020, coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, was declared as a global pandemic by the World Health Organization (WHO). To date, there are rapidly spreading new “variants of concern” of SARS-CoV-2, the United Kingdom (B.1.1.7), the South African...

www.biorxiv.org