SARS-cov-2 spike protein activates endotoxin receptor TLR4

[Mauritio]

Many people die of sepsis when they get covid .
This study shows that the SARS-cov-2 spike protein activates the endotoxin receptor TLR4.
Interestingly this was completely unrelated to its abilty to bind to ACE2 .
So the spike protein induces inflammation in at least two ways: inhibition of ACE2 and activation of TLR4 .

The spike protein was capable of dose-dependentoy increasing interleukin 1b . So the more spike protein, the more inflammation.

"Accumulating clinical data suggest the main causes of death by COVID-19 include respiratory failure and the onset of sepsis.1 Importantly, sepsis has been observed in nearly all deceased patients.2"

"Consistently, we found that the induction of IL1B by SARS-CoV-2 was completely blocked by TLR4-specific inhibitor Resatorvid"

"Results of the surface plasmon resonance (SPR) assay showed that SARS-CoV-2 spike trimer directly bound to TLR4 with an affinity of ~300 nM (Fig. 1b), comparable to many virus-receptor interactions."

"Collectively, SARS-CoV-2 spike protein is capable of interacting with and activating TLR4."

"...spike protein of SARS-CoV-2 was able to induce a number of immune-related genes, including interleukins, chemokines and IFN-stimulated genes (ISGs) (Fig. 1p, q; Supplementary information, Fig. S1s)."

"Treatment with ACE2 inhibitor (MLN-4760) or soluble ACE2 was not able to inhibit the induction of IL1B by LPS or spike protein (Supplementary information, Fig. S1p, q)."

"Thus, activation of TLR4 by spike protein was not regulated by ACE2 and TMPRSS2 or virus entry."

(SARS-CoV-2 spike protein interacts with and activates TLR41)

 

[Mauritio]

Btw the inflammation was completely reversible by using a TLR4 antagonist (Resatorvid - Wikipedia)

This makes already established covid treatments like vitamin D and aspirin even more valuable since they're also TLR4 antagonists.
Vitamin D is "anti-covid" in several ways: it reduces cytokines, it antagonizes TLR4 and it binds to the spike protein directly .
So by that logic other TLR4 agonists should work as well. Here are some suggestios:

Pregnenolone Is A Potent (functional) Endotoxin (TLR4) Antagonist

It seems that pregnenolone is finally starting to look exciting to the medical industry. In addition for its intensive studies for a variety of mental issues, now studies are coming out demonstrating its endotoxin (LPS) antagonism effects. As most forum users know, endotoxin exerts its effects...

raypeatforum.com

Lidocaine Is An Endotoxin (TLR4) Antagonist

In this study, Lidocaine protects kidneys and liver from endotoxin by down-regulating TLR4 receptor. It's not antagonist at receptor, actually it downregulates the receptor which means a better mechanism. Lidocaine protects against renal and hepatic dysfunction in septic rats via downregulation...

raypeatforum.com

Glycine Is An Endotoxin (TLR4) Antagonist

We can now add glycine to the substances that inhibit endotoxin or its effects. The endotoxin antagonism probably explains a good deal of glycine's protective effects on the liver from all sorts of assaults, but especially ethanol/alcohol (which is a known TLR4 agonist). The in-vivo study used a...

raypeatforum.com

Vitamin B2 (riboflavin) Is Endotoxin (LPS / TLR4) Antagonist

This is just a follow up on the recent post on both riboflavin and vitamin D. Vitamin B2 Remarkably Effective Against Endotoxin, Sepsis, And Other Bacterial Infections https://raypeatforum.com/community/threads/vitamin-d-is-endotoxin-lps-tlr4-antagonist-may-treat-lps-linked-conditions.12060/...

raypeatforum.com

Vitamin A (retinol) Is Endotoxin (LPS / TLR4) Antagonist

Another one in the series of endotoxin antagonism featuring so far vitamins D and B2. Vitamin B2 (riboflavin) Is Endotoxin Antagonist Vitamin B2 Remarkably Effective Against Endotoxin, Sepsis, And Other Bacterial Infections Vitamin D Is Endotoxin (LPS / TLR4) Antagonist, May Treat LPS-linked...

raypeatforum.com

Vitamin D Is Endotoxin (LPS / TLR4) Antagonist, May Treat LPS-linked Conditions

The activation of TLR by various substances like endotoxin, ethanol / alcohol, opioids, SSRI, etc is involved in the pathogenesis of many conditions, especially IBD, colon cancer, periodontal disease, etc. There are very few effective endotoxin antagonists in clinical use, which is unfortunate...

raypeatforum.com

Progesterone May Bind And Deactivate Endotoxin (LPS) Directly

I made a few posts recently discussing the blocking effects of pregnenolone on TLR4 and TLR family receptors in general, and the reduction of systemic inflammation stemming from this blockade/regulation...

raypeatforum.com

 

[Mauritio]

"There is a link between high lipopolysaccharide (LPS) levels in the blood and the metabolic syndrome, and metabolic syndrome predisposes patients to severe COVID-19. Here, we define an interaction between SARS-CoV-2 spike (S) protein and LPS, leading to aggravated inflammation in vitro and in vivo."

"Taken together, our results provide an interesting molecular link between excessive inflammation during infection with SARS-CoV-2 and comorbidities involving increased levels of bacterial endotoxins."

(SARS-CoV-2 spike protein binds to bacterial lipopolysaccharide and boosts proinflammatory activity - PubMed)

 

[dmorbelo]

Many people die of sepsis when they get covid .
This study shows that the SARS-cov-2 spike protein activates the endotoxin receptor TLR4.
Interestingly this was completely unrelated to its abilty to bind to ACE2 .
So the spike protein induces inflammation in at least two ways: inhibition of ACE2 and activation of TLR4 .

The spike protein was capable of dose-dependentoy increasing interleukin 1b . So the more spike protein, the more inflammation. View attachment 30626



"Accumulating clinical data suggest the main causes of death by COVID-19 include respiratory failure and the onset of sepsis.1 Importantly, sepsis has been observed in nearly all deceased patients.2"

"Consistently, we found that the induction of IL1B by SARS-CoV-2 was completely blocked by TLR4-specific inhibitor Resatorvid"

"Results of the surface plasmon resonance (SPR) assay showed that SARS-CoV-2 spike trimer directly bound to TLR4 with an affinity of ~300 nM (Fig. 1b), comparable to many virus-receptor interactions."

"Collectively, SARS-CoV-2 spike protein is capable of interacting with and activating TLR4."

"...spike protein of SARS-CoV-2 was able to induce a number of immune-related genes, including interleukins, chemokines and IFN-stimulated genes (ISGs) (Fig. 1p, q; Supplementary information, Fig. S1s)."

"Treatment with ACE2 inhibitor (MLN-4760) or soluble ACE2 was not able to inhibit the induction of IL1B by LPS or spike protein (Supplementary information, Fig. S1p, q)."

"Thus, activation of TLR4 by spike protein was not regulated by ACE2 and TMPRSS2 or virus entry."

(SARS-CoV-2 spike protein interacts with and activates TLR41)

I wonder if the TLR4 issue is from the spike protein and explains why we are seeing tinnitus following vaccinations.

 

[Mauritio]

What do you mean by TLR4 issue ?

 

[aliml]

I wonder if the TLR4 issue is from the spike protein and explains why we are seeing tinnitus following vaccinations.

In Traditional Chinese Medicine, tinnitus is often related to dysfunction of the Kidney, and TLR4 activation is associated with kidney injury.

TLR4 activation mediates kidney ischemia/reperfusion injury

Ischemia/reperfusion injury (IRI) may activate innate immunity through the engagement of TLRs by endogenous ligands. TLR4 expressed within the kidney is a potential mediator of innate activation and inflammation. Using a mouse model of kidney IRI, we ...

www.ncbi.nlm.nih.gov

 

[Perry Staltic]

Importantly, sepsis has been observed in nearly all deceased patients.

All, or nearly all, deceased covid patients were put on ventilators. Mechanical ventilation (MV) activates TLR4, which starts a cascade of inflammatory signaling leading to sepsis. This is called mechanotransduction, ie, transformation of a mechanical force (air pressure) into biochemical signaling.

Previous experimental studies have shown that injurious mechanical ventilation has a direct effect on pulmonary and systemic immune responses. How these responses are propagated or attenuated is a matter of speculation. The goal of this study was to determine the contribution of mechanical ventilation in the regulation of Toll-like receptor (TLR) signaling and interleukin-1 receptor associated kinase-3 (IRAK-3) during experimental ventilator-induced lung injury.
...
High VT mechanical ventilation for 4 hours was associated with a significant increase of TLR4 ...

Mechanical ventilation modulates TLR4 and IRAK-3 in a non-infectious, ventilator-induced lung injury model - PubMed

The current study supports an interaction between TLR4 and IRAK-3 signaling pathway for the over-expression and release of pro-inflammatory cytokines during ventilator-induced lung injury. Our study also suggests that injurious mechanical ventilation may elicit an immune response that is similar...

pubmed.ncbi.nlm.nih.gov

They really don't know what causes sepsis. They also can't separate the two signals of sepsis and ventilator-induced lung injury. In other words they can't tell if MV is causing sepsis.

The symptoms of severe covid and sepsis are identical. They can't separate the signals.

So how do they know a virus rather than mechanical ventilation is responsible for the bad outcomes?

They don't.

 

[Mauritio]

All, or nearly all, deceased covid patients were put on ventilators. Mechanical ventilation (MV) activates TLR4, which starts a cascade of inflammatory signaling leading to sepsis. This is called mechanotransduction, ie, transformation of a mechanical force (air pressure) into biochemical signaling.

Mechanical ventilation modulates TLR4 and IRAK-3 in a non-infectious, ventilator-induced lung injury model - PubMed

The current study supports an interaction between TLR4 and IRAK-3 signaling pathway for the over-expression and release of pro-inflammatory cytokines during ventilator-induced lung injury. Our study also suggests that injurious mechanical ventilation may elicit an immune response that is similar...

pubmed.ncbi.nlm.nih.gov

They really don't know what causes sepsis. They also can't separate the two signals of sepsis and ventilator-induced lung injury. In other words they can't tell if MV is causing sepsis.

The symptoms of severe covid and sepsis are identical. They can't separate the signals.

So how do they know a virus rather than mechanical ventilation is responsible for the bad outcomes?

They don't.

Why not both?

 

[Perry Staltic]

In Traditional Chinese Medicine, tinnitus is often related to dysfunction of the Kidney, and TLR4 activation is associated with kidney injury.

Mechanical ventilation (MV) activates inflammatory cascades that promote de novo synthesis of adhesion molecules (thrombotic precursors) in organs distal to the lungs (eg, kidneys). Microclotting causes organ damage.

Our data implicate that MV causes endothelial activation and inflammation in mice without pre-existing pulmonary injury, both in the lung and distal organs.

Ventilator-induced endothelial activation and inflammation in the lung and distal organs

Results from clinical studies have provided evidence for the importance of leukocyte-endothelial interactions in the pathogenesis of pulmonary diseases such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), as well as in systemic ...

www.ncbi.nlm.nih.gov

 

[Perry Staltic]

Why not both?

To be able to distinguish what causes what we would need clear signals. We don't have that because everyone who dies gets intubated. How do you separate the signals?

 

[David PS]

Why not both?

I agree. It could be a deadly combination.

 

[Mauritio]

To be able to distinguish what causes what we would need clear signals. We don't have that because everyone who dies gets intubated. How do you separate the signals?

I think it might be both, a deadly combination as @David PS said.

 

[Perry Staltic]

I think it might be both, a deadly combination as @David PS said.

The way mechanical ventilation is being used now, it would be deadly in combination with anything. MV can kill a perfectly healthy person by itself.

The data suggest that covid is not particularly deadly (99+% survival rate).

So the bad outcomes likely aren't due to some kind of synergy between the two, but rather to the associated medical response that is deadly.

 

[Perry Staltic]

I wonder if the TLR4 issue is from the spike protein and explains why we are seeing tinnitus following vaccinations.

Since the clot shots turn people into spike protein producing factories, perhaps TLR4 antagonists might be useful in remediating their damage potential.

 

[Perry Staltic]

Natural Products with Toll-Like Receptor 4 Antagonist Activity

Toll-Like Receptors (TLRs) are the innate immunity receptors that play an activating role when interacting with molecules released by bacteria and viruses (PAMPs, pathogen-associated molecular patterns) or with molecules released by injured cells and tissues (DAMPs, danger-associated molecular...

www.hindawi.com

 

[Mauritio]

The way mechanical ventilation is being used now, it would be deadly in combination with anything. MV can kill a perfectly healthy person by itself.

The data suggest that covid is not particularly deadly (99+% survival rate).

So the bad outcomes likely aren't due to some kind of synergy between the two, but rather to the associated medical response that is deadly.

Possible, but it has been shown in 2005 already that the spike protein is harmful to the lungs ,so I wouldn't discard that possibility entirely.

 

[Perry Staltic]

Natural Products with Toll-Like Receptor 4 Antagonist Activity

Toll-Like Receptors (TLRs) are the innate immunity receptors that play an activating role when interacting with molecules released by bacteria and viruses (PAMPs, pathogen-associated molecular patterns) or with molecules released by injured cells and tissues (DAMPs, danger-associated molecular...

www.hindawi.com

The molecules of natural origin with well-demonstrated TLR4 antagonist activity, currently reported in the literature, were LPS and lipid A from Rhodobacter sphaeroides, LOS from Bartonella quintana, LPS from Oscillatoria Planktothrix FP1, curcumin from Curcuma longa, sulforaphane and iberin from cruciferous vegetables, xanthohumol from hops and beer, celastrol from Tripterygium wilfordii.

The last one is called Thunder God Vine. What a name for a botanical.

 

[Perry Staltic]

Possible, but it has been shown in 2005 already that the spike protein is harmful to the lungs ,so I wouldn't discard that possibility entirely.

I think using TLR4 antagonists as treatment/prophylaxis for covid is a great idea, but possibly more so for clot shot remediation.

 

[LadyRae]

Btw the inflammation was completely reversible by using a TLR4 antagonist (Resatorvid - Wikipedia)

This makes already established covid treatments like vitamin D and aspirin even more valuable since they're also TLR4 antagonists.
Vitamin D is "anti-covid" in several ways: it reduces cytokines, it antagonizes TLR4 and it binds to the spike protein directly .
So by that logic other TLR4 agonists should work as well. Here are some suggestios:

Pregnenolone Is A Potent (functional) Endotoxin (TLR4) Antagonist

It seems that pregnenolone is finally starting to look exciting to the medical industry. In addition for its intensive studies for a variety of mental issues, now studies are coming out demonstrating its endotoxin (LPS) antagonism effects. As most forum users know, endotoxin exerts its effects...

raypeatforum.com

Lidocaine Is An Endotoxin (TLR4) Antagonist

In this study, Lidocaine protects kidneys and liver from endotoxin by down-regulating TLR4 receptor. It's not antagonist at receptor, actually it downregulates the receptor which means a better mechanism. Lidocaine protects against renal and hepatic dysfunction in septic rats via downregulation...

raypeatforum.com

Glycine Is An Endotoxin (TLR4) Antagonist

We can now add glycine to the substances that inhibit endotoxin or its effects. The endotoxin antagonism probably explains a good deal of glycine's protective effects on the liver from all sorts of assaults, but especially ethanol/alcohol (which is a known TLR4 agonist). The in-vivo study used a...

raypeatforum.com

Vitamin B2 (riboflavin) Is Endotoxin (LPS / TLR4) Antagonist

This is just a follow up on the recent post on both riboflavin and vitamin D. Vitamin B2 Remarkably Effective Against Endotoxin, Sepsis, And Other Bacterial Infections https://raypeatforum.com/community/threads/vitamin-d-is-endotoxin-lps-tlr4-antagonist-may-treat-lps-linked-conditions.12060/...

raypeatforum.com

Vitamin A (retinol) Is Endotoxin (LPS / TLR4) Antagonist

Another one in the series of endotoxin antagonism featuring so far vitamins D and B2. Vitamin B2 (riboflavin) Is Endotoxin Antagonist Vitamin B2 Remarkably Effective Against Endotoxin, Sepsis, And Other Bacterial Infections Vitamin D Is Endotoxin (LPS / TLR4) Antagonist, May Treat LPS-linked...

raypeatforum.com

Vitamin D Is Endotoxin (LPS / TLR4) Antagonist, May Treat LPS-linked Conditions

The activation of TLR by various substances like endotoxin, ethanol / alcohol, opioids, SSRI, etc is involved in the pathogenesis of many conditions, especially IBD, colon cancer, periodontal disease, etc. There are very few effective endotoxin antagonists in clinical use, which is unfortunate...

raypeatforum.com

Progesterone May Bind And Deactivate Endotoxin (LPS) Directly

I made a few posts recently discussing the blocking effects of pregnenolone on TLR4 and TLR family receptors in general, and the reduction of systemic inflammation stemming from this blockade/regulation...

raypeatforum.com

Great information! Thank you! I enjoy all your posts, even if I usually don't comment. I have still SO much to learn ( more than I thought I did LOL) ?

 

[LadyRae]

Since the clot shots turn people into spike protein producing factories, perhaps TLR4 antagonists might be useful in remediating their damage potential.

Lots of people are getting boosters. And you're never going to know who is who when you go into the grocery store or something you know? Last spring, my husband unfortunately got the J&J vaccine, and two days later I started a super-heavy 10 day period even though I was right in the middle of my cycle. Really scary. Now I know that his body was producing Mass amounts of Spike protein and circulating it around the house. Our teen daughter also had a strange cycle that month.

I have made an effort to be very factual and non-emotional in providing information about the vaccines that won't make me sound too conspiratorial or something, and he is not opting for a booster thank goodness.....

He is a bit overweight and he watches regular news twice a day( honestly I think this is the worst vaccination brainwashing) and I really have tried to be compassionate towards his fear, but offer alternatives.