SARS-CoV-2, the Spike Protein and Oncogenesis

How the SARS-CoV-2 and its Spike Protein cause Cancer by mimicking (and perhaps inducing) Cancer’s genetic altering of cellular functions.

Virtually everyone has some knowledge of the fact that Cancer is caused by the accumulation of somatic mutations. However, for cancer to occur, these mutations must alter cellular functions in one or more of the following categories:

·         DNA Repair

·         Cell Division

·         Apoptosis

·         Cellular Differentiation

·         Cell-Cell Contact/Communication

SARS-CoV-2 and its Spike Protein alter ALL these functions. This can explain why dormant cancer cells can become activated and why Cancer may appear de novo. Let us review each of the above cellular functions in relation to the Spike Protein and infection with SARS-CoV-2. Please note that the Spike Protein alone can induce many of these alterations.

DNA REPAIR

A paper which has been “retracted” clearly identifies the mechanism by which the Spike Protein impairs DNA repair:

Our findings provide evidence of the spike protein hijacking the DNA damage repair machinery and adaptive immune machinery in vitro. We propose a potential mechanism by which spike proteins may impair adaptive immunity by inhibiting DNA damage repair. Although no evidence has been published that SARS–CoV–2 can infect thymocytes or bone marrow lymphoid cells, our in vitro V(D)J reporter assay shows that the spike protein intensely impeded V(D)J recombination. Consistent with our results, clinical observations also show that the risk of severe illness or death with COVID–19 increases with age, especially older adults who are at the highest risk. This may be because SARS–CoV–2 spike proteins can weaken the DNA repair system of older people and consequently impede V(D)J recombination and adaptive immunity.

I have extensively reviewed this paper and can find no reason why it should have been retracted. The science is extremely sound. However, I am certain others have found reason to retract it:

Furthermore, our findings also imply a potential side effect of the full–length spike–based vaccine. This work will improve the understanding of COVID–19 pathogenesis and provide new strategies for designing more efficient and safer vaccines.

SARS–CoV–2 Spike Impairs DNA Damage Repair and Inhibits V(D)J Recombination In Vitro
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538446/

CELL DIVISION

Interaction between the negative C-terminals of tubulin and the central point of the receptor-binding domain of the spike protein embedded in the membrane of the SARS-CoV-2 virion. Mapping of electrostatic potential (red = negative charge, blue = positive charge) was carried out using the VMD molecular graphics software package for both the execution of APBS and the visualization of the resulting electrostatic potentials. Force field parameters such as atomic charges and radii were assigned using the PDB2PQR webserver (http://server.poissonboltzmann.org, accessed on 29 May 2021).

The Spike Protein impairs the cell division process. It does this by hijacking the microtubule cytoskeleton.

Here we consider how the SARS-CoV-2 virus may “hijack” cytoskeletal functions by docking inside the microtubule-organizing center’s centriole “barrels”, enabling certain interactions between the virus’s positively charged spike (“S”) proteins and negatively charged C-termini of the microtubules that the centriole comprises, somewhat like fingers on a keyboard.

Moreover, linked by microtubule spindles, the two cylinders replicate and separate to initiate cell division/mitosis and establish daughter cell shape.

For example, in mitosis/cell division, centrosomes replicate and separate to pull apart duplicate sets of chromosomes by means of microtubule mitotic spindles to establish daughter cell genome and architecture.

How COVID-19 Hijacks the Cytoskeleton: Therapeutic Implications
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9225596/

CELLULAR DIFFERENTIATION

SARS-CoV-2 infection causes global loss of cellular m6A RNA methylation. This loss of function disrupts the regulation of, among other processes, cell differentiation. The referenced paper does not indicate which viral proteins are involved in this loss of function.

N6-Methyladenosine modification (m6A) is a prevalent internal RNA modification (Baquero-Perez et al. 2021). It is involved in the regulation of a broad range of biological processes including cell differentiation (Geula et al. 2015), mRNA stability, translation, liquid-phase separation, and stress granule formation, among others (Zaccara et al. 2019)… Thus, our data suggest that loss of m6A during SARS-CoV-2 infection establishes a pattern of host cell gene expression that favors viral replication.

Yet, even though the paper does not specifically indicate that the Spike Protein is the cause, it is heavily suggestive.

We observed that infected HNEs were positive for spike protein and showed disturbed staining of cilia marker TUBB4A as reported earlier (Supplemental Fig. S7D; Robinot et al. 2021). Taken together, our observations in multiple transformed and primary cell culture models suggest that SARS-CoV-2 infection causes a global loss of m6A in cellular RNA.

Global loss of cellular m6A RNA methylation following infection with different SARS-CoV-2 variants
https://genome.cshlp.org/content/33/3/299.full

CELL-CELL CONTACT/COMMUNICATION

The Spike Protein is found in extracellular vesicles, which are responsible for cellular communication.

“Extracellular vesicles” (EVs) is the term used to define a family of membrane bodies released from almost all cell types having an important role in cellular communication (van Niel et al. 2022; Díaz-Godínez et al. 2022).

Surprisingly (or not) vaccination alone leads to the induction of extracellular vesicles which carry the Spike Protein.

To determine the mechanism, we analyzed the kinetics of induction of circulating exosomes with SARS-CoV-2 spike protein and Ab following vaccination of healthy individuals. Results demonstrated induction of circulating exosomes expressing spike protein on day 14 after vaccination followed by Abs 14 d after the second dose. Exosomes withs pike protein, Abs to SARS-CoV-2 spike, and T cells secreting IFN-g and TNF-a increased following the booster dose.

Cutting Edge: Circulating Exosomes with COVID Spike Protein Are Induced by BNT162b2 (Pfizer-BioNTech) Vaccination prior to Development of Antibodies: A Novel Mechanism for Immune Activation by mRNA Vaccines
https://pubmed.ncbi.nlm.nih.gov/34654691/

APOPTOSIS

This dysregulation is a special case. The Spike Protein induces Apoptosis, which is generally a good thing as it prevents Cancer cells from living and dividing uncontrollably. However, it is still dysregulated. Moreover, this process may contribute to the other observed pathological effects of the Spike Protein.

The dysregulation of apoptosis is a symptom in a wide variety of diseases. Accelerated apoptosis is found in infertility, immunodeficiency, and acute and chronic degenerative diseases, and delayed or inhibited apoptosis is present in cancer and autoimmunity.

Apoptosis: A Target for Anticancer Therapy
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5855670/

It is clear that the tremendous increase in cancers may have a definitive cause in SARS-CoV-2 and its Spike Protein. If you read the literature, this understanding is becoming ever more prevalent. I will continue to study the work of others and contribute to our overall knowledge of this virus and its proteins. I will also continue to find therapeutics to treat it.

Thank you for your continued support.