An Analysis of Pathologies and Their Origin.
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Introduction
This report will cover the biomechanisms involved with the Spike protein for SARS-CoV-2 as well as various pathogenic responses it is known to elicit. We will begin with the natural observation of the spike protein’s role in cellular infection and end with an examination of the public health theory of using a vaccine based on spike protein during an active pandemic. Individual protein and genetic markers within the spike protein as well as their effects will be provided. In the end, it will be completely clear to anyone reading that the Spike protein for COVID-19 is the causative agent for “Long Covid”, which the HHS labels as a disability under the Americans with Disabilities Act (ADA), and MUST be designated a biologic toxin, and informed consent for vaccines expanded to include a warning for the possibility of a Healthcare-associated infection.
Let us Begin with Natural Infection to grasp S1 sui pathogenesis.
Spike Protein Role in Natural Infection
The role of the spike protein in natural infection is well-known. A brief explanation of its properties help provide context for understanding reported observations.
Coronavirus disease 2019 is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The spike (S) protein of SARS-CoV-2, which plays a key role in the receptor recognition and cell membrane fusion process, is composed of two subunits, S1 and S2. The S1 subunit contains a receptor-binding domain that recognizes and binds to the host receptor angiotensin-converting enzyme 2, while the S2 subunit mediates viral cell membrane fusion by forming a six-helical bundle via the two-heptad repeat domain.
A large number of glycosylated S proteins cover the surface of SARS-CoV-2 and bind to the host cell receptor angiotensin-converting enzyme 2 (ACE2), mediating viral cell entry. When the S protein binds to the receptor, TM protease serine 2 (TMPRSS2), a type 2 TM serine protease located on the host cell membrane, promotes virus entry into the cell by activating the S protein. Once the virus enters the cell, the viral RNA is released, polyproteins are translated from the RNA genome, and replication and transcription of the viral RNA genome occur via protein cleavage and assembly of the replicase–transcriptase complex. Viral RNA is replicated, and structural proteins are synthesized, assembled, and packaged in the host cell, after which viral particles are released.
https://www.nature.com/articles/s41401-020-0485-4
The above link provides further details on the function and structure of SARS for the purpose of finding a pharmacological solution. However, the foundation of the solution the article provides is based on preventing ACE2 binding, or the utilization of spike as a therapeutic target. TMPRSS2, being a natural enzyme necessary for cellular intrusion and therefore clinical infection, listed in the article as “activating the S protein”, is a target completely ignored.
Spike Protein Structure
The S1 subunit has 2 sections itself: Receptor Binding Domain (RBD) and the N-Terminal Domain (NTD). RBD must be in an “up” or “opened” position in order to bind with ACE2.
The fusion peptide (FP) (788–806 residues), heptapeptide repeat sequence 1 (HR1) (912–984 residues), HR2 (1163–1213 residues), TM domain (1213–1237 residues), and cytoplasm domain (1237–1273 residues) comprise the S2 subunit.
a Schematic representation of the SARS-CoV-2 spike.
b–c The S protein RBD closed and opened status.
d The S protein binds to ACE2 with opened RBD in the S1 subunit.
e The six-helix structure formed by HR1 and HR2 of the S2 subunit.
Observed Pathogenicity of Spike Protein
Acute lung injury (ALI) leading to acute respiratory distress syndrome is the major cause of COVID-19 lethality. Intratracheally instilled S1 subunit of SARS-CoV-2 spike protein (S1SP) in K18-hACE2 transgenic mice that overexpress human ACE2 [showed] signs of COVID-19-associated lung injury 72 h later.
K18-hACE2 mice that received either saline or whole SP exhibited little or no evidence of lung injury. Wild Type mice that received S1SP exhibited a milder form of COVID-19 symptoms, compared with the K18-hACE2 mice. Furthermore, S1SP, but not full spike protein, decreased cultured human pulmonary microvascular transendothelial resistance (TER) and barrier function.
https://journals.physiology.org/doi/full/10.1152/ajplung.00223.2021
Researchers Show How SARS-COV-2 Spike Protein Causes Acute Lung Injury in Mice
This is the first demonstration of a COVID-19-like response by an essential virus-encoded protein by SARS-CoV-2 in vivo.
This mouse study serves as clinical evidence of the pathogenic nature of the S1 spike protein on its own. Evidence of decreased microvascular transendothelial resistance (TER) is AT LEAST enough for a warning of this specific pathological result in vivo. However, it is not the only study with pathogenic findings for the spike protein.
Data reveals that S protein alone can damage endothelium, manifested by impaired mitochondrial function and eNOS activity but increased glycolysis. It appears that S protein in Endothelial Cells(EC’s) increases redox stress which may lead to AMPK (AMP-activated protein kinase) deactivation, MDM2 (murine double minute 2) upregulation, and ultimately ACE2 destabilization
Mitochondrial fragmentation caused by S1 binding to ACE2 is an unbelievably important finding, as is the data showing impairment of Endothelial Nitric Oxide Synthase (eNOS). eNOS impairment means less Nitric Oxide (NO2), which leads to vasodilation impairment, an increase in VEGF (Vascular endothelial growth factor) leading to increased localized cellular proliferation, and reduced antithrombotic activity due to reduced NO2 available to inhibit platelet activation. NO2 is also known to inhibit Nuclear factor kappa B (NF-κB), which means NO2’s absence or inhibition may cause an increase in NF-kB, leading to inflammation and increased binding of the immune system on the cell.
Increased intracellular glycolysis: Glycolosis produces an increase in reactive oxygen species (ROS). Not normally a cause of concern on its own, but with reduced Nitric Oxide also comes a reduction in Superoxide dismutase (SOD). Limited SOD means less available to counteract ROS, especially when glycolysis is elevated. ROS may reach such a level as to disrupt or destabilize ACE2 receptors.
AMPK is directly responsible for the creation of the ACE2 receptor in the cell. AMPK deactivation means the cell’s ability to make the ACE2 receptor is inhibited. MDM2 is necessary to express an ACE2 receptor on the cell surface. An upregulation of MDM2 means any ACE2 receptor lucky enough to be created in an already inhibitory environment is still going to have a hard time making it to the cell membrane to function at all.
The ACE1/ACE2 receptor balance is responsible for the inflammatory response. ACE1 is inflammatory in nature, and ACE2 is anti-inflammatory in nature. If ACE2 is destabilized intracellularly then inflammatory markers of ACE1 will become dominant as well. Keep in mind all of these effects were observed occurring due to the SPIKE PROTEIN ALONE.
https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.121.318902
Spike Protein Cytotoxicity – COVID-19 Primarily A Vascular Disease
Syncytia & Lymphocyte Elimination
Heterotypic cell-in-cell structures with lymphocytes inside multinucleated syncytia are prevalent in the lung tissues of coronavirus disease 2019 (COVID-19) patients. The expression of the SARS-CoV-2 spike glycoprotein is sufficient to induce a rapid (~45.1 nm/s) membrane fusion to produce syncytium, which could readily internalize multiple lines of lymphocytes to form typical cell-in-cell structures, remarkably leading to the death of internalized cells.
A unique bi-arginine motif with the polybasic S1/S2 cleavage site (FCS) of SARS-CoV-2 spike glycoprotein was identified to be capable of controlling this process by which syncytia, resulted from SARS-CoV-2 infection, could target infiltrated lymphocytes for internalization and CIC mediated death, contributing to lymphopenia in the patients.
Syncytia are a single cell or cytoplasmic mass containing several nuclei, formed by fusion of cells or by division of nuclei. Lymphocytes, aka White blood Cells, play a protective role in your immune system: B lymphocytes – T lymphocytes – Natural killer cells. Lymphopenia (also called lymphocytopenia) is a disorder in which your blood doesn’t have enough Lymphocytes (i.e. immune cells, antibodies).
https://www.nature.com/articles/s41418-021-00782-3
S1 Inflammagen & Fibrinogenic Activity
A study on the effect of isolated SARS-CoV-2 spike protein S1 subunit showed it as a potential inflammagen sui generis. Using scanning electron and fluorescence microscopy as well as mass spectrometry, this study investigated the potential of (S1) inflammagen to interact with platelets and fibrinogen directly to cause blood hypercoagulation. Using platelet-poor plasma (PPP), it has been found that the spike protein interferes with blood flow. Mass spectrometry also showed that when spike protein S1 is added to healthy PPP, it results in structural changes to β and γ fibrin, complement 3, and prothrombin. These proteins were substantially resistant to trypsinization, in the presence of spike protein S1.
Trypsinization is the process of cell dissociation using trypsin, a proteolytic enzyme which breaks down proteins, to dissociate adherent cells from the vessel in which they are being cultured. Changes to fibrin structure made them adhere to endothelial cells in a way natural processes are unable to remove or dissolve.
Whereas SARS-CoV-2 is widely considered an airborne respiratory virus, it is IMPOSSIBLE to ignore the effects on the vascular system. The prevalence of pathologies resulting from S1 are now observed outside the cell with direct interaction and mutation of fibrin proteins, which creates an additional set of vascular pathologies.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380922/
Clots | Blood Vessel Damage – This Is The Most Important Lecture for COVID
*Reminder of the role S1 plays in natural infection: How it is separated from the virus at the furin cleavage site (FCS) by TMPRSS2, and remains outside of the cell after cellular intrusion by the virus.
Further reading on Fibrinogen & Fibrin: https://ashpublications.org/blood/article/126/17/1977/34431/Not-fibrin-ogen-but-fibrinogen-or-fibrin
Amyloidogenesis
Amyloid fibril assays of peptide library mixtures and theoretical predictions identified seven amyloidogenic sequences within the S-protein. Three 20-amino acid long synthetic spike peptides (sequence 192–211, 601–620, 1166–1185) fulfilled three amyloid fibril criteria: nucleation dependent polymerization kinetics by ThT, Congo red positivity, and ultrastructural fibrillar morphology. Full-length folded S-protein did not form amyloid fibrils, but amyloid-like fibrils with evident branching were formed during 24 h of S-protein coincubation with the protease neutrophil elastase (NE) in vitro.
NE efficiently cleaved (activated) S-protein, rendering exposure of amyloidogenic segments and accumulation of the amyloidogenic peptide 194–203, part of the most amyloidogenic synthetic spike peptide. NE is overexpressed at inflamed sites of viral infection.
Amyloidosis is associated with cerebral amyloid angiopathy, blood coagulation disruption, fibrinolytic disturbance, FXII Kallikrein/Kinin activation, and thromboinflammation, suggesting potential links between S-protein amyloidogenesis and COVID-19 phenotypes.
https://pubs.acs.org/doi/10.1021/jacs.2c03925#
One major causal factor of Alzheimers disease is known to be extracellular amyloid beta (Abeta) accumulated senile plaques. Thus amyloidogenesis, as its own pathology caused by the S1-subunit, may have additional cascading effects within human physiology. In this context, amyloid cascade hypothesis, neuroinflammation, oxidative stress, granulovacuolar degeneration, loss of Wnt signaling, Abeta-related synaptic alterations, prolonged calcium ions overload and NMDAR-related synaptotoxicity, and damage signals hypothesis.
https://pubmed.ncbi.nlm.nih.gov/33539020/
Micro-Clotting
SARS-Cov-2-induced infection, the cause of coronavirus disease 2019 (COVID-19), is characterized by unprecedented clinical pathologies. One of the most important pathologies is hypercoagulation and microclots in the lungs of patients.
During the progression of the various stages of the COVID-19, markers of viral replication, as well as von Willebrand factor (VWF) and fibrinogen depletion with increased D-dimer levels and dysregulated P-selectin levels, followed by a cytokine storm, are likely to be indicative of a poor prognosis. This poor prognosis is further worsened as together with a substantial deposition of microclots in the lungs. Plasma of COVID-19 patients also carries a massive load of preformed amyloid clots, and there are also numerous reports of damage to erythrocytes, platelets, and dysregulation of inflammatory biomarkers.
Receptor binding is certainly responsible for cell-mediated pathologies, but does not itself explain the coagulopathies. Spike protein, can however be shed, and it has been detected in various organs, including the urinary tract. S1 proteins can also cross the blood–brain barrier. Free S1 particles play a role in the pathogenesis of the disease.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380922/
The fibrin(ogen) production serves like a biological net or glue. The trapping of VWF itself has a host of known thrombolytic implications – Von Willebrand factor (VWF) contributes to the pathogenesis of atherosclerosis, the development of arterial and venous thrombosis, and thromboembolic risks in people with atrial fibrillation. VWF inhibition may lead to its own CDC defined disease – https://www.cdc.gov/ncbddd/vwd/facts.html
https://www.sciencedirect.com/topics/medicine-and-dentistry/von-willebrand-factor
Markers used to identify clotting factors become entangled within the S1 induced fibrin structure, and will NOT show up on normal lab tests searching for those markers. It is thus preferred to conduct a TEG Scan (Thromboelastography), to determine the prevalence of the S1 modified fibrin structures and presence of microclots.
Research suggests starting antiplatelet and anticoagulants early on, with professional care, during the initial acute phase if possible. In dire or chronic cases apheresis may have a positive outcome. Another suggestion was Heparin induced, extracorporeal, lipoprotein/fibrinogen precipitation.
Interview with Dr. Resia Pretorius: LongCovid microclots (spike protein, apheresis + other topics)
https://youtu.be/C8tzTmVwEpM Details of Microclotting Papers By Prof. Resia Pretorius https://youtu.be/fflt95jPUYM
Thrombotic Thrombocytopenia
Thrombotic thrombocytopenic purpura is a rare disorder that causes blood clots (thrombi) to form in small blood vessels throughout the body. These clots can cause serious medical problems if they block vessels and restrict blood flow to organs such as the brain, kidneys, and heart.
This is a disease where microclots lead to bleeding. This diagnosis is the reason the FDA limited Johnson & Johnson vaccines to over 18 year-olds. With everything preceding this, we have laid the foundation for the set of S1 induced pathologies leading to this life-threatening disorder.
https://www.cnbc.com/2022/05/05/fda-limits-use-of-jjs-covid-19-vaccine-for-adults.html
S1 – Alpha7 nAChR Activation
Alpha7 nicotinic acetylcholine receptor (α7 nAChR) is an important part of the cholinergic nerve system in the brain. Moreover, it is associated with a cholinergic anti-inflammatory pathway in the termination of the parasympathetic nervous system.
AChR activation will influence enzyme acetylcholinesterase (AChE) availability in the neurosynaptic cleft normally present to quickly terminate the Acetylcholine (ACh) neurochemical signal.
Antagonists of α7 nAChR are a wide group represented by conotoxin and bungarotoxin. Alzheimer’s disease drug memantine acting as an antagonist in its side pathway belongs in this group. Agonists of α7 nAChR are suitable for treatment of multiple cognitive dysfunctions such as Alzheimer’s disease or schizophrenia.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3292018/
S1 epitope coincides with the well-described cryptic epitope for the human antibody CR3022 and with the epitope for the recently described COVA1-16 antibody.
The NCS is an important pathway which regulates the response to inflammation. Its effects on macrophages and other immune cells are mainly regulated by the vagus nerve and by alpha7 nicotinic acetylcholine receptors (nAChRs). This so-called “cholinergic anti-inflammatory pathway” has been found beneficial in preventing inflammatory conditions such as sepsis and Acute Respiratory Distress Syndrome (ARDS) in animal models. Dysregulation of the NCS could therefore be a possible cause for the uncontrolled inflammatory response in COVID-19.
SARS-CoV-2 S1 glycoproteins (A7J8L4, P0DTC2) with Neurotoxin homolog NL1 (Q9DEQ3). SARS-CoV-2 Receptor Binding Domain (RBD) (aa 306-527) Spike glycoproteins (the domain through which the spike protein recognizes the ACE2 on the host’s cell surface) neighboring to the ACE2 Receptor Binding Motif (aa 437-508). This sequence is exposed while spike protein is in a closed/down position and after S1 is cleaved.
https://www.biorxiv.org/content/10.1101/2020.08.20.259747v1.full
ARDS – Cytokine Storm
Cytokines are any of a number of substances, such as interferon, interleukin, and growth factors, which are secreted by certain cells of the immune system and have an effect on other cells.
Cytokine storm and cytokine release syndrome are life-threatening systemic inflammatory syndromes involving elevated levels of circulating cytokines and immune-cell hyperactivation. Cytokine Storm is the clinical cause of mortality; Its removal and reduction is the goal of any clinician.
ADE, or Antibody Dependent Enhancement will be expanded on in Part 2. However it is important to note the immune system’s presence in the bundle of cells included in the Cytokine mesh.
Acute respiratory distress syndrome (ARDS) is a serious lung condition that causes low blood oxygen. People who develop ARDS are usually ill due to another disease or a major injury.
In ARDS, fluid builds up inside the tiny air sacs of the lungs, and surfactant breaks down.
https://www.nhlbi.nih.gov/health/ards
Pulmonary surfactant is a surface-active complex of phospholipids and proteins formed by type II alveolar cells.[1] The proteins and lipids that make up the surfactant have both hydrophilic and hydrophobic regions. By adsorbing to the air-water interface of alveoli, with hydrophilic head groups in the water and the hydrophobic tails facing towards the air, the main lipid component of surfactant, dipalmitoylphosphatidylcholine (DPPC), reduces surface tension.
This may also be characterized as decreased cultured human pulmonary microvascular transendothelial resistance (TER) and barrier function as discussed earlier in “Observed Pathogenicity of Spike Protein”. ARDS appears to be a lung diagnosis when S1 induced cytokines sui generis cascade into numerous inflammatory pathologies.
Sui Pathogenesis – Intermission
“The Science” necessitates observable reality. Long Covid is an extension of pathologies (Sequelae) occurring during the acute phase via S1 sui pathogenesis. Inflammation has many characteristics and consequences. Knowing the S1 sui pathogenesis cascade provides a context to understand its chronic phase, conditions, and sequelae.
Understanding acute S1-induced physiologies provides a foundation to approach PASC (Post-Acute Severe Covid, aka Post-Acute Sequelae Covid19), Long Covid, Multi-System Inflammatory Syndrome (MIS-C), Myocarditis, Hepatitis, etc.
Diagnosing “inflammation” is akin to prescribing Motrin in the military. Whereas specialists are trained to label inflammation in an organ with a specific word, greater understanding needs to be given to the characteristics and specific pathophysiologies resulting in abnormal growth and function.
When the “experts” finally get around to telling you the originating cascade for a host of chronic conditions now being seen in the actuarial tables of life insurance agencies as a 40% increase in all-cause mortality, rest assured you have already read what you would expect them now to tell you…
CDC “Harmless” Semantics?
ALL VACCINES TARGET the S1 subunit for production.
https://www.nature.com/articles/s41541-021-00369-6
For some reason the CDC refers to the spike protein as “harmless”.
Knowing what we know now, how is it possible to call the spike protein harmless?
Now we will go into the immune response, and finish with Long Covid, which *spoiler alert* is caused by spike protein.
Please take a moment to digest this: How is it possible for S1 sui pathogenesis to be known to “Average Person” using peer-reviewed publicly available research and information, yet NOT provided for Informed Consent by “public health experts”, WHO officials, or other mandating entity?
S1 is a toxin
American Foundation for Informed Consent 
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