Friday Hope: Spermidine: Clearing the Spike Protein

Autophagy may be one of the best strategies for clearing the pathogenic Spike Protein.

Overview of the autophagy pathway during viral infection. 1. ACE2/TMPRSS2 mediated endocytosis. 2. Replication of virus inside ER-derived DMVs containing LC3-I. 3. Induction of early stages of autophagy and accumulation of autophagosomes. 4. Viral proteins block the fusion event between autophagosomes and lysosomes, thereby blocking late stages of autophagy. 5. MHC-mediated presentation of viral particles upon autophagic degradation. Created with BioRender.com. 

ACE2 = angiotensin converting enzyme-2; DMV = double membraned vesicles; ER = endoplasmic reticulum; LC3 = microtubule-associated protein 1A/1B-light chain 3B; MHC = major histocompatibility complex; TMPRSS2 = a type II transmembrane serine protease 

If you have been following my work, you will know that I now believe Long COVID is not a disease unto itself. I believe there is ample evidence to show that Long COVID is actually Persistence of the Spike Protein. We still need to determine if this persistence is due to the virus hiding in parts of the body, the Spike Protein retrotranscribing itself, or a combination of the two. 

Could SARS-CoV-2 Spike Protein Be Responsible for Long-COVID Syndrome? 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8757925/ 

I have delved into ways for the body to naturally rid itself of this pathogenic protein. After weeks of reading, I conclude that Autophagy is perhaps the best place to start detoxifying the body from this pathogen. 

First, what is Autophagy? 

Autophagy (pronounced “ah-TAH-fah-gee”) is your body’s process of reusing old and damaged cell parts. Cells are the basic building blocks of every tissue and organ in your body. Each cell contains multiple parts that keep it functioning. Over time, these parts can become defective or stop working. They become litter, or junk, inside an otherwise healthy cell. 

Autophagy is your body’s cellular recycling system. It allows a cell to disassemble its junk parts and repurpose the salvageable bits and pieces into new, usable cell parts. A cell can discard the parts it doesn’t need. 

Autophagy is also quality control for your cells. Too many junk components in a cell take up space and can slow or prevent a cell from functioning correctly. Autophagy remakes the clutter into the selected cell components you need, optimizing your cells’ performance. 

Autophagy is essential for a cell to survive and function. Autophagy: 

• Recycles damaged cell parts into fully functioning cell parts. 

• Gets rid of nonfunctional cell parts that take up space and slow performance. 

• Destroys pathogens in a cell that can damage it, like viruses and bacteria. 

Autophagy plays an important role when it comes to aging and longevity, too. As a person ages, autophagy decreases, which can lead to a build-up of cellular junk parts and, in turn, cells that aren’t functioning at their best. 

Autophagy 
https://my.clevelandclinic.org/health/articles/24058-autophagy 

Shortly after the beginning of the Pandemic, researchers discovered that Autophagy inducers demonstrated great potential to inhibit the REPLICATION of SARS-CoV-2. 

Early on during the first wave of infections in April, a group from the virology department at Berlin’s Charité showed great potential for autophagy modulators, including spermidine, Akt (protein kinase B) inhibitor MK-2206 and Beclin-1 stabilising niclosamide, to inhibit SARS-CoV-2 propagation (preprint, not peer-reviewed) [10]. Many of the more promising compounds currently investigated in clinical trials are indeed autophagy modulators, thus substantiating the need for an understanding of how coronaviruses interact with and utilise components of the autophagy pathway. 

Autophagy is a multistep process for lysosomal degradation of cytoplasmic content such as damaged organelles, protein aggregates or long-lived proteins, and hence ensures a supply of biomass in times of nutrient starvation and stress. Although there are different subtypes of autophagy depending on cargo recognition and the method of delivery to the lysosome, we focus solely on macroautophagy for the purposes of this article. Macroautophagy (hereafter autophagy) traps cytoplasmic contents through the formation of a thin membrane around the cargo, called the phagophore, which furthermore expands and closes to become the double-membraned autophagosome. 

Autophagy and coronavirus infection – a Trojan horse or Achilles heel? 
https://smw.ch/index.php/smw/article/view/2942/4845 

Later, it was discovered (given that Autophagy degrades protein aggregates and long-lived proteins (see above) that Autophagy likely CLEARS THE SPIKE ITSELF through these mechanisms. 

4.4. Clearing Spike Protein 

So far, we have discussed ways to inhibit the impacts of the spike protein on the host’s system. Importantly, to progress beyond this, it is necessary to clear out the spike protein. This can be accomplished through upregulation of the protein degradative pathways in the body through upregulation of autophagy. Autophagy can be upregulated by fasting [170] and calorie restriction, especially if protein is reduced. Autophagy in many instances does not require the complete cessation of food intake (protocols are available at https://COVID19criticalcare.com/treatment-protocols/, accessed on 15 April 2023). Sharply decreasing protein intake can upregulate autophagy pathways, and this can be accomplished while still eating, which makes this more approachable as a protocol. Regular fasting was also associated with better outcomes from acute COVID-19. 

Spermidine, a polyanion compound found in high concentrations in wheat germ, can potently stimulate autophagy. 

Moreover, many other compounds we have discussed as being beneficial in combatting the Spike Protein – are also inducers of Autophagy! 

Other factors which influence autophagy are acute heat exposure, as one would experience in a sauna, flavonoid consumption, phenolic compounds, and coffee. Resveratrol can also induce fasting, as it acts as a protein restriction mimetic, and metformin, a diabetes medication, can influence autophagy signaling. Surprisingly, cold exposure, in addition to heat exposure, also increases autophagy. Hyperbaric oxygen and ozone therapy may also stimulate autophagy. 

Strategies for the Management of Spike Protein-Related Pathology 
https://www.mdpi.com/2076-2607/11/5/1308 

I urge clinicians to investigate the use of Autophagy induction in their treatment of patients with Spike Protein and COVID-related pathologies.