Spike Protein S2 inhibits p53 (cancer implications)

And some blood - regeneration stuff

Some days things just happen. Today is one of those days. To start it off, for a couple of years now I have been wondering what is hiding inside the S2 part of the Spike Protein because all the evidence pointed towards quite a few possible “threats” there.

Spike protein S2 enhances amyloid-β production

So you can imagine my surprise when this was published late yesterday.

SARS-CoV-2 spike S2 subunit inhibits p53 activation of p21(WAF1), TRAIL Death Receptor DR5 and MDM2 proteins in cancer cells

This paper is not very long, but it is complex, and it was written, on purpose so they could even upload the paper as a pre-print. So far the entire p53 (a master regulator of cancer, together with another protein and…a forgotten enzyme…) hinged on bioinformatics for the most part, an actual model was never tried, probably because of the hot potato aspect of the topic. Other papers measured p53 levels, which can increase in response to cellular stress.

Also before going any further, this study was done in cancer cell lines, which obviously affects the outcomes, and the Spike Protein here is overexpressed. It does NOT invalidate the research, but it is something to be very aware of.

First, the authors tested what Spike overexpression would do to these cancer cells, and if there was any interaction between Spike, p53, and MDM2. MDM2 is a negative regulator of p53, a way for the body to avoid “overcorrection”, it is a very important protein. They observed that abundant S2 impacted the binding of p53 and MDM2 in cancer cells, but they couldn’t observe the S2 binding with p53. They also weren’t able to observe the Spike getting inside the nucleus of the cell but there was a minuscule quantity inside some cells, so they couldn’t discard it.

Remember, whatever goes on in the nucleus of the cell is of extreme importance, and this is the only place where I would “disagree” with the authors They didn’t observe, but there is more than one mechanism by which S2 or the entire Spike Protein can get to the nucleus.

Their next step was a investigate if or how SARS-CoV-2 Spike S2 affected p53 signaling in these cancer cells. They how active p53 is in the presence of S2 and found out that it was less active, and even when using drugs to make p53 more active (cisplatin causes DNA damage, which activates p53) or Nutlin-3a (it stops MDM2 and makes p53 more active) the Spike S2 made p53 less active.

They found that the SARS-CoV-2 spike S2 reduces the transcriptional activity of p53. This means that when the SARS-CoV-2 spike S2 subunit protein is present, the p53 protein isn’t able to do its job of starting transcription as effectively.

So far the findings are concerning, but their next step was more concerning. They continued their research and this time used a chemotherapy model, using 2 types of cancer cells, MCF7 a breast cancer cell (ironically… it has estrogen receptors…), and H460 a lung cancer cell, and introduced S2 in them. Then they treated these cells with 2 chemotherapy drugs, etoposide and 5-Fluorouracil.

They found that the cells with S2 in them showed less p53 activity compared to the control cells, this means the S2 may reduce the activity of p53 in chemotherapy. Next, they look at the levels of specific proteins that are usually controlled by p53, p21, TRAIL Death Receptor DR5, and MDM2 were lower or their levels increased slowly when S2 was present. So in the chemotherapy scenario, the S2 affects the p53 signaling potentially affecting growth arrest and cell death (important for cancer).

Since p53 is involved in DNA damage response as repair they next examined this by analyzing y-H2AX (a marker for DNA damage) levels in cancer cells. They found that y-H2AX levels were lower in the cells with Spike S2 in them, suggesting that S2 might change how the cancer cells sense and repair DNA damage.

In the author’s finishing remarks.

Our results have implications for the biological effects of spike S2 subunit in human cells whether spike is present due to primary COVID-19 infection or due to mRNA vaccines where its expression is used to promote anti-viral immunity. A perturbed p53 pathway is concerning but also complicated in sorting out since cellular transformation and cancer are a multi-step process that evolves over time. Further detailed studies can more fully characterize the effects of spike, as well as structural determinants within the protein for interaction between the DNA damage sensing and response pathways as well as the p53 tumor suppressing pathway. With respect to the p53 pathway, further studies are needed to unravel how less MDM2 is bound to p53 in the presence of spike and the mechanisms underlying reduced p21(WAF10), TRAIL Death Receptor DR5 as well as MDM2 under conditions where there is less degradation of p53 due to reduced interaction with MDM2

In summary, we identified the SARS-CoV-2 spike S2 subunit as a COVID-19 virus factor that interrupts p53 binding to MDM2 in cancer cells and demonstrated the suppressive effect of SARSCoV-2 spike S2 on p53 signaling in cancer cells. Correlated to the inhibition of p53 signaling, the short-term expression of spike S2 caused an altered DNA damage response through altered levels of g-H2AX after DNA damage in cells, altered sensing in the damage response to cisplatin Importantly, the p53-dependent DNA damage induction of growth arrest and apoptotic targets p21(WAF1) and TRAIL Death Receptor DR5 was significantly attenuated under different experimental conditions with spike S2 and this was associated with greater cell viability in the presence of spike S2 and chemotherapy treatment. As loss of p53 function is a known driver of cancer development and confers chemo-resistance, our study provides insight into cellular mechanisms by which SARS-CoV-2 spike S2 may be involved in reducing barriers to tumorigenesis during and post SARS-CoV-2 infections.

Cancer is complex, it is most of the time paradoxical, you will find conflicting evidence for each and every mechanism if you look long enough. The Spike Protein and the virus itself have multiple mechanisms to induce or accelerate cancer, I covered many here, latent viruses reactivation, affecting and disrupting fungal immunity, setting of bacterial infection sensitivity (getting infected by bacteria all the time), all contribute to cancer onset and growth.

SARS-CoV-2 and the Oncogenes pathway

But here, we have a plausible mechanism in which the Spike alone in a limit setting can accelerate the growth, especially if the mechanism described here causes Mutant p53, leading to “turbo cancers” (a point brought up by Paul Traynor bsc). I was surprised the authors found lower levels of y-H2AX, but this may be their model using cancer cell lines, or the type of cells, those being breast and lung.

But this vindicates two older papers that are very important. The first, was where they found that the Spike Protein caused indirect damage to cardiomyocytes (heart cells), by lowering P53, but found higher levels of y-H2AX.

SARS-COV-2 elevated DNA damage risk in cardiomyocytes without direct infection

The second is among the most important ones, which I buried in a longer article on purpose.

SARS-CoV-2 - Impaired DNA repair, viral evolution, and secondary infections

In the author’s own words, this paper was heavily criticized at the time.

Mechanistically, we found that the spike protein localizes in the nucleus and inhibits DNA damage repair by impeding key DNA repair protein BRCA1 and 53BP1 recruitment to the damage site. Our findings reveal a potential molecular mechanism by which the spike protein might impede adaptive immunity and underscore the potential side effects of full-length spike-based vaccines.

Does all of these mechanism have a unique aspect to it ? A protein to rule them all ? And what else is hiding in the S2 ?

I will now finish my Omicron article and publish it in the next few days since it is extremely important, but before… how about some conspiracy for your night ?

You, an intellectual - There is no reason for powerful people to consume the blood of young children
Me, a schizo - The blood of young children regenerates the old
The science →

I really appreciate your support, thank you !

Me tired of these horrors within comprehension