SARS-CoV-2 Spike aggregation and LPS

Into the chasm we go

This is one I have been waiting for ages to write. I will first cover the paper and introduce a whole host of things.

SARS-CoV-2 spike protein aggregation is triggered by bacterial lipopolysaccharide

The first part of this paper is pretty straightforward and somewhat easy to understand. If you don’t know what an LPS is, here you can read a pretty extensive paper about it, the short of it is the LPS is part of the membrane of bacteria with potent effects inside the human body. It is a potent activator of the Toll-Like Receptor 4 pathway, which can both fend off “disease” and feed in inflammatory responses.

Previously the author showed the Spike protein, both “parts” interacted with LPS, and now they went further to show regions that are prone to form aggregates are nearby the sites that binds (glue) to LPS, which have physiological and long-term effects.

Here they use a software-based predictive application to analyze the possible binding sites to find the regions with the highest possible score for aggregation, those being loop 246-250 of the NTF, loop 621-624 of the CTD2. Ironically enough, the loop is fairly close to the peptide sequence 601-620, which forms amyloid fibrils when the S protein is co-incubated with neutrophil elastase (neutrophil-secreted enzyme to break down specific types of proteins).

To not overcomplicate things but worth mention both of the sites discussed above are also close to the novel CTSL cleavage site that facilitates viral infection, and thanks to a friend, both of these CTSL sites are incredibly close to the GP120 inserts… what are the odds huh ?

Here authors argue about the structure of the Spike protein and the formation of protein complexes and how stable they are. Both shape and stability of proteins are among the most important aspects of molecular biology, arguably everything else is secondary.

Going to further argue there are other regions surrounding the LPS binding sites which can lead to further aggregation, forming larger complexes. Binding of smaller molecular such as heme metabolites on the NTD can induce profound changes in the shape of that region of the Spike Protein.

The closing remarks of the paper are rather simple to understand. At a low concentration of LPS, the Spike can and will induce large amounts of inflammatory response via TLR4 pathway, and at higher concentrations, the same sites, under certain conditions may induce the formation of amyloid, especially via the S protein “glued” to LPS interacting with other proteins that can form amyloid.

In summary, because it is about to get slightly complicated, a few places in the Spike Protein can bind (glue) themselves with one of the nastier parts of bacteria, the Lipopolysaccharide, exerting both inflammatory and potential neurodegenerative effects on the body under specific conditions. I would argue most of these rather complex effects of the Spike are under “specific conditions”.

First, the reader should understand, I have been hinting at the Spike Protein interacting with endotoxins for a looooong while, and I said it was via protein interaction, a few people can confirm the extension of my idea. In fact, it was at the same time I started researching the PAID hypothesis with a friend.

A part of a piece from February

The paper above is remarkable because it “proves” one of my observations which I never proposed publicly, just among a few people, which we just discussed. The Spike Protein, certain peptides sequence, “parts” of the Spike will interact with other proteins and create not aggregates and reactions. I will go further and present another one, the Spike itself, via similar “conditions” will also create endotoxic reactions, via protein interaction.

An insane proposition as far as 3 days ago, now circumstantial, but one day might be proved possible. Now we go old school. As Daoyu pointed out shortly before his ban, the Spike sequence is by itself a membrane piercer, meaning it will cut through other membranes, and more often than not, given the poor quality control many vaccinated will have the Spike floating around and doing damage.

Even if we ignore this, what do most severe, ICU and Long Covid patients have in common, besides poor metabolic, highly inflammatory markers and dysfunctional immune systems ? A severely imbalanced microbiome, which is a one-way street towards LPS going around you. Now that we have a few common links between Spike, bacteria, and LPS and its possible interactions, we can connect a few dots.

Iron overload accelerates neuronal amyloid-β production and cognitive impairment in transgenic mice model of Alzheimer's disease, here you also have an extensive paper on the relation between Iron dysregulation and amyloidogenesis, the first being a known effect of SARS-CoV-2 infection (and vaccination but this one evidence is harder to come by).

It also has known that LPS will increase levels of the neurotoxic metabolite of the Kynurenine Pathway, Quinolinic Acid, and also Kynurenic Acid (which can be neuroprotective), but in certain conditions, especially in regards to LPS it may cause behavioral and cognitive deficits.

Before finishing this piece, I will now show you the last reference.

Elevated amyloidoses of human IAPP and amyloid beta by lipopolysaccharide and their mitigation by carbon quantum dots

Type 2 diabetes (T2D) and Alzheimer's disease (AD) represent two most prevalent amyloid diseases with a significant global burden. Pathologically, T2D and AD are characterized by the presence of amyloid plaques consisting primarily of toxic human islet amyloid polypeptide (IAPP) and amyloid beta (Aβ). It has been recently revealed that the gut microbiome plays key functions in the pathological progression of neurological disorders through the production of bacterial endotoxins, such as lipopolysaccharide (LPS).

This study revealed a robust synergy between LPS and amyloid peptides in toxicity induction, and implicated CQDs as a potential therapeutic against the pathologies of T2D and AD.

The study above shows a high synergy between LPS and amyloid peptides exerting a toxic function in the human body. In case the reader is not aware IAPP is also known as Amylin, but there is another name it is used to be referred to. Amylin Islet Polypeptide, otherwise named AIP.

Now I want you to go to the piece below, look for the image below “These are the genes Interleukin-12 can up and down-regulate.” There is something between the protein MIF and SOD1, do you what those letter are ?

PAID Part III—Welcome to the Super Family

Oh…

As I have been aggressively stating, to the point of blocking most of Alt-Covid, this is how far back 2 people have been on the amyloidogenesis aspect of this, and this is how complex truly it is. You will understand more about how amylin connects to the rest in the Kynurenine Pathway Part II.

For the average reader or anyone else, I have already written about how to mitigate or “negate” these interactions, and it still stays the same. Proteolytic enzymes as Serratiopeptase and Nattokinase (Lumbrokinase if you have access), NAC or Liposomal Glutathione for a little bit of the Iron aspect, and some others. In fact, the circumstances where propagation of misfolded protein and amyloid will occur are somewhat stringent conditions, which most of the “stack” takes care of.

But the paper above as a sizable step in the right direction, leading the way to finally connecting “impossible” dots.

A mechanistic deep dive for the ones inclined would be going back into many of my other pieces. Yes, almost every single piece I wrote about SARS-CoV-2 is in fact one hypothesis. If you want some nightmare fuels this one is quite good too.

Have a nice day whenever you are reading this.

Massive appreciation to all supporters here and on Kofi !!!