Another Spike Protein Parallel to Radiation Damage: DNA Double Strand Breaks

DNA damage from radiation causes the expression of γ-H2AX. So does the Spike Protein.

Simplified representation of the DNA-damage-induced checkpoint response. Ionizing radiation induces DNA breaks. After the detection of a given damage by sensor proteins, this signal is transduced to the effector protein CHK2 via the transducer protein ATM. This ATM activation induces γ-H2AX formation, used as a biomarker for DNA breaks. Depending on the phase of the cell cycle the cell is in, this can lead to activation of p53 and inactivation of CDC25, which eventually leads to cell cycle arrest. Mediator proteins mostly are cell cycle specific and associate with damage sensors, signal transducers, or effectors at particular phases of the cell cycle and, thus, help provide signal transduction specificity. The effect of UV light is via the transducer protein ATR and the effector protein CHK1. MRE11 meiotic recombination 11, NBS1 Nijmegen breakage syndrome 1, ATM ataxia telangiectasia mutated, ATR ataxia telangiectasia related, γ-H2AX phosphorylated form of Histone variant 2AX, MDC1 mediator of DNA damage checkpoint 1, 63BP p63 binding protein, BRCA1 breast cancer 1, TopBP1 topoisomerase binding protein 1, CHK1 check 1, CHK2 check 2, CDC25 cell division cycle 25, G1 gap 1, S synthesis, G2 gap 2, M mitosis

I am continuing my study of the Spike Protein and how its actions mimic that of radiation. Radiation, as is widely known, causes DNA Double Strand Breaks (DSBs). This leads to the expression of γ-H2AX, the gold standard biomarker for DNA damage.

Within hours, ionizing irradiation induces DNA strand breaks that lead to ataxia telangiectasia mutated (ATM) phosphorylation. As a result, the histone H2AX is phosphorylated within seconds, which is termed γ-H2AX and is radiation dose-dependent [69, 70]. It is evident that the γ-H2AX formation is correlated with DNA strand breaks [71]. Increases in γ-H2AX formation are found in mice [72], Gottingen minipigs [73] and non-human primates [74]. The γ-H2AX foci formation was found in peripheral blood lymphocytes and plucked hairs, suggesting a robust biodosimeter for analyzing partial body exposure to ionizing radiation in humans [74].

Radiation: a poly-traumatic hit leading to multi-organ injury
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6417034/

This is also precisely what the Spike Protein induces.

In vitro studies have shown that the SARS-CoV-2 spike protein inhibits DNA damage repair by impeding the recruitment of DNA damage repair checkpoint proteins, a pre-requisite for V(D)J recombination in adaptive immunity. This has further been confirmed in spike protein over expressed cells by upregulation of DNA damage marker γ-H2AX.

Transcriptomic profiling of cardiac tissues from SARS-CoV-2 patients identifies DNA damage
https://www.medrxiv.org/content/10.1101/2022.03.24.22272732v1.full

We observed an increase in the DNA damage response marker γ-H2AX in cells transfected with the viral spike gene. γ-H2AX was found to be localized to the nucleus in viral spike-transfected A549 cells. Our results indicated that SARS-CoV-2 spike protein expression induces a senescent state in spike-transfected A549 cells that is associated with the DNA damage response and increased ROS generation.

SARS-CoV-2 Spike Protein Induces Paracrine Senescence and Leukocyte Adhesion in Endothelial Cells
https://journals.asm.org/doi/10.1128/jvi.00794-21

While this is concerning, it is my current thinking that treatments limiting and ameliorating DNA damage may be helpful in the treatment of COVID and Spike Protein-related disease, and in preventing and treating Long COVID. I will be working on defining these potential therapeutics.