Conspiracy Friday - MERS and the Bioengineering Conundrum

A molecular clamp a day brings the plague to stay

I am currently in the middle of nowhere, with never-ending rain, and barely any meaningful high-speed connection sometimes no connection at all, therefore no AI-podcast to help you this time =P.

A week prior to Christmas a specific paper was published, an interesting one at that, fit to some of my more… unorthodox ideas.

Pre-pandemic artificial MERS analog of polyfunctional SARS-CoV-2 S1/S2 furin cleavage site domain is unique among spike proteins of genus Betacoronavirus

Objectives

SARS-CoV-2 spike (S) glycoprotein furin cleavage site is a key determinant of SARS-CoV-2 virulence and COVID-19 pathogencity. Located at the S1/S2 junction, it is unique among sarbecoviruses but frequently found among betacoronaviruses. Recent evidence suggests that this site includes two additional functional motifs: a pat7 nuclear localization signal and two flanking O-glycosites. However, a systematic genus and subgenus analysis of spike protein sequences bearing this polyfunctional sequence domain has been missing.

Data description

Here we report comprehensive sequence data to demonstrate that among spike proteins of genus Betacoronavirus and outside of the SARS-CoV-2 clade a fully analogous S1/S2 domain was found in only one other virus: the artificial MERS infectious clone MERS-MA30, described already in 2017, which was rationally selected from serial passage in genetically humanized mice. As the evolutionarily closest betacoronaviruses outside of the SARS-CoV-2 clade lack all its three functional motifs, these data extend—beyond natural evolution and zoonosis—the current view on SARS-CoV-2 pre-pandemic origins by presenting the analogous S1/S2 MERS-MA30 sequence domain as a precise molecular blueprint for SARS-CoV-2.

Collectively, these data suggest that, within genus Betacoronavirus, MERS-MA30 S1/S2 spike—a year 2017 or earlier product of directed adaptation and rational selection in an artificial (i.e., genetically engineered) murine host—is the only instance of a complete pat7/FCS/O-glycosite composite motif fully analogous to the S1/S2 polyfunctional spike sequence domain of SARS-CoV-2.

In simpler terms, the author of this paper analyzed the data of different coronaviruses with a specific focus on what enabled SARS-CoV-2 to infect humans, and to our own hypothesis, enabled it to become a Neo-polymorphic Toxin, its Furin Cleavage Site. In this comparison, the only other coronavirus that is a perfect analog (copy) of SARS-CoV-2 was MERS-MA30 CoV.

MA-30 is a synthetic, lab-engineered, and serially passaged “copy” of MERS. MA-30 only attained a perfect FCS analog by serially passaging in humanized mice. This means repeatedly infecting mice with a virus, collecting the sample, “growing” more of this virus that infected a bunch of humanized mice, repeat the process until you achieve the desired result or gather sufficient data to study.

The data analysis by itself already hinders the arguments of natural origins, but this also leads to evidence and credence to my and a few other’s hypotheses (including Chinese researchers btw) that someone has been tinkering and releasing coronaviruses as field tests since the first SARS-CoV outbreak.

At the odd turns and highly important discoveries, MERS is often cited. SARS-CoV-2 Spike Protein can interact and induce a “leaky gut” by interacting with both CEACAM5 and Galectin-9. CEACAM5 can help MERS infect cells. Galectin-9 plays an essential and crucial role in HIV.

Divergent T-cells and forgetful B-cells

A direct quote from the article above.

In simplistic terms, this explains why there is a huge discrepancy at different points in time in the pandemic between vaccinated X unvaccinated, viral loads, and viral spread, at least initially. It can also explain some viral rebound cases at the time. And given it is the weekend, your conspiracy for it will be, it is interesting that both MERS-CoV (which has a similar Furin Cleavage Site to SARS-CoV-2), and SARS-CoV-1 also induce short-lived antibodies.

One of my primary and largest interests is superantigens, together with toxins. That PRRAR sequence is all-in-one. All the letters in the “C” section in the image form a multifunctional protein. It is the cleavage site, it also mimics one of the most powerful toxins known to science (SEB), and it also can mimic Neisseria Meningitis (another powerful toxin). Ironically it also mimics a part of HIV (GP120).

Also as a matter of interest, there is another HIV insert in the sequences above, the “135” one, HKNNKS. Here is where things get complicated. There is a measurable difference in how the T-cell responses between unvaccinated and vaccinated, with each group of immune cells targeting specific sequences.

The unvaccinated will often target the superantigenic region, while the vaccinated target other regions, there is an overlap, but there are distinct T-cell responses between the two.

SARS-CoV, MERS, and especially SARS-CoV-2 all contain a “Galectin-fold” an almost perfect mimic of human Galectin-3.

Chimeric nature of Galectin-3 and SARS-CoV-2

In 2015 the UNC experienced a series of lab accidents that could potentially lead to a leak, and I have in good authority (a former lab worker) that 8 people there got infected with a severe form of pneumonia… in 2017. This entire article goes back to here.

Conspiracy Monday - Virology Nostradamus

Despite a very specific, driven purely by self-interest clique of professionals (virologists) pushing the narrative for 2 decades that SARS-CoV came from bats, MERS-CoV came from camels, there is no conclusive proof, there is circumstantial evidence. And with its added features throughout the years, some arising only via precise engineering, the question remains.

MERS-CoV, SARS-CoV-1, and SARS-CoV-2 share certain structural and functional characteristics. SARS-CoV-2's S1/S2 region includes not only the furin cleavage site but also:

• Mimics of superantigens, such as the bacterial SEB toxin.

• Structural homology to HIV-1 GP120 and Neisseria meningitis toxins.

• Galectin-fold structures, which closely resemble human Galectin-3.

The “PRRAR” sequence in SARS-CoV-2 i It functions as a furin cleavage site while mimicking multiple potent toxins and immune-evading structures and is a small section of HIV’s GP120. Additionally, the presence of sequences like "HKNNKS" is also an GP120 piece, so is “GTNGTKR” known as the Galectin-fold, and “TPGDSSG”.

GP120 one of the world’s most known and likely used molecular clamp, imagine it as a customized Lego block, enabling you to “glue” 2 small proteins together that don’t quite fit well, but with a molecular clamp, they become stable. Each of these sequences play more than one role in the viral infection, and consequentially the lasting sequelae, and I now refer to them as “Multifunctional scaffold motifs”, scaffolds are proteins that work as “building blocks” for more complex proteins.

Someone has been playing a very long game. A conspiracy thought for the end of your year. Also if you want a deep dive into a far more complex and vast analysis on the complexity of these sequences, many of my most recent articles are related to this topic. I prefer keeping things separeted.

It should go without saying but given the absurd amount of rain, power sometimes going out, and lack of proper mobile connection, articles may lag until I return home.

If I was a Prussian, probably…