Another HIV "piece" in the Spike Protein

Blues clues remix here

I was supposed to publish my next Beyond Mathematical Odds focused on Deindustrialization, but events all day made it difficult, I could finish it very late but rather take my time in the face of this.

Earlier today, little past midnight, a paper was published. About how the Spike Protein and its mRNA can get inside the nucleus of cells by using a novel site, that site is one of the GP120-HIV inserts. I won’t cover that one here, but perhaps now researchers will start looking at what is happening at the nucleus.

I don’t expect it to reverse transcribe to be clear, I know the majority of people interested in this do think it will happen.

If you don’t recall, The Many Faces of the Spike Protein is basically talking about the functionality of the HIV inserts, each of them with a nasty function. One is a supersite for antibodies, basically fueling immune evasion of new variants, the other one is a novel cleavage site for the Spike Protein (so you don’t need Furin, you have an alternative method…), and the third one was a Galectin-3 mimic, which I will get to writing it. If you didn’t get it, high levels of Galectin-3 + IgG4 = diseases galore.

The reason for writing this one was this, and a stupid observation I had yesterday.

Flap structure within receptor binding domain of SARS-CoV-2 spike periodically obstructs hACE2 Binding subdomain bearing similarities to HIV-1 protease flap

This is a fairly touchy subject, the “HIV inserts” are not even widely accepted, let alone accepted as functional proteins, so the authors are very broad and light in their description in this “review”, they are even afraid to call their short paper, a scientific paper.

Beta Hairpin is a very rudimentary but important secondary structure that often connects different proteins, they are also essential for protein folding. Here this flap (hairpin) is described as a potential modulator of binding activity of the Receptor Binding Domain with human ACE2 receptors, similar to what happens in HIV, in which a similar structure modulates which type of receptor the V3 loops use.

As I wrote a couple of weeks ago, conformation (shape of the protein) matters a lot sometimes, which leads us to the following paragraph.

Specifically, residues V395-L518 in the Up-state protomer exhibit no dominant energetic interactions with its neighboring N-terminal Domain (NTD) protomer, as expected, whereas numerous residues in the same region of the Down-state protomer exhibited strong interactions with neighboring NTD protomer residues helping to keep this binding subdomain “hidden” and less available for hACE2 binding.

Depending on which state (shape) certain regions of the virus are in, they either have no effect or strong effects, but the part that is “most important” to me is the highlighted one. One of my focuses the last 8 weeks has been the non-canonical side of almost everything. Non-canonical roles of antibodies, the non-canonical function of proteins, non-canonical proteins, non-canonical usually means “not much studied”, or “pathway/mechanism yet to be fully uncovered”.

I had a stupid observation in between researching these topics, which was there are buried sequences in this, that will affect the interaction and conformation of the Spike, exposing cryptic (hidden) sites having unexpected effects. One of these stupid ideas I had last year was the Spike Binding with endotoxins, which now we know does bind to Lipopolysaccharides. < Also the section that binds to LPS is one of the HIV inserts… ops.

Another was that something changed the conformation around the Galectin-3 fold (NTD) exposing a cryptic site and eliciting an unusual molecular response. Outlandish up until earlier today.

It is safe to just say it now that there are cryptic functions all over the Spike Protein sequence, and depending on its conformation (shape) it either “activates” said function, or remains buried, without doing much. Other aspects of my stupid observation and research do apply but I would get way ahead of myself for now. Non-canonical proteins have more functions and are often much overlooked by researchers than canonical ones too, a topic to delve into if you like this subject matter.

Safe to say, the Spike Protein is like a Rubib’s Cube of viruses, and they will find many hidden things and functions inside it.

And there are people who say with a straight face this came from nature lmao.

Much appreciation for all supporters and subscribers who share the work if they find it useful.