Friday Hope: Inhibiting Cell Adhesion Dysregulation Induced by the Spike Protein: Vioprolide A
Anti-inflammatory and leukocyte-endothelial cell interaction blocking properties
Readers of my Substack may recall that earlier this year I revisited my hypothesis that the Spike Protein induces an Endothelial Disease. I then hypothesized that the evidence pointed towards the condition actually being a disease of Cell Adhesion dysregulation.
https://wmcresearch.substack.com/p/permanent-endothelial-activation
A paper published last month provides evidence that this may indeed be the case.
It is known that S protein from SARS-CoV-1 and SARS CoV-2 binds to the extracellular domain of angiotensin-converting enzyme 2 (ACE2) to infect the epithelial cells (12, 13). However, other cell entry mechanisms of SARS-CoV-2 have been strongly suggested (14). The recently evolved SARS CoV-2 S protein RGD motif (aa403-405) within the receptor binding domain (RBD) has been proposed to bind platelet integrin αIIbβ3 (7, 15). The RGD motif is not present in the S proteins from any other known human or bat coronavirus, but the KGD motif (lysine/glycine/aspartic acid), which is located at position aa390-392 in the SARS CoV-1 S protein RBD (16), is also able to bind αIIbβ3 integrin (4). The KGD motif is present also in the S proteins from so-called “bat SARS-like” coronaviruses, such as, RaGT13, WVI1, RsSHC014, Rs3367, and HKU3 (17).
Besides fibrinogen, other acute phase proteins such as prothrombin and vWF are integrin αIIbβ3 ligands, and they also use the RGD motif to bind activated platelets (18). Fibrinogen also binds to integrin α5β1 on endothelial cells via the carboxyl-terminal RGD sequence (aa572-574) of α-chain with high affinity (Kd = 65 nM), which have broad biological implications.
Are the integrin binding motifs within SARS CoV-2 spike protein and MHC class II alleles playing the key role in COVID-19
https://www.frontiersin.org/articles/10.3389/fimmu.2023.1177691/full
Therefore, I believe it may be important that those exposed to the Spike Protein, or those with active COVID/Spike Protein-related Disease find way to ameliorate the cell adhesion dysregulation. The naturally product Vioprolide A may be a natural treatment to address this dysregulation. Please note that it “hits all the right notes” in dealing with Spike Protein pathologies.
Chronic inflammation is characterized by persisting leukocyte infiltration of the affected tissue, which is enabled by activated endothelial cells (ECs). Chronic inflammatory diseases remain a major pharmacotherapeutic challenge, and thus the search for novel drugs and drug targets is an ongoing demand. We have identified the natural product vioprolide A (vioA) to exert anti-inflammatory actions in vivo and in ECs in vitro through inhibition of its cellular target nucleolar protein 14 (NOP14). VioA attenuated the infiltration of microglia and macrophages during laser-induced murine choroidal neovascularization and the leukocyte trafficking through the vascular endothelium in the murine cremaster muscle. Mechanistic studies revealed that vioA downregulates EC adhesion molecules and the tumor necrosis factor receptor (TNFR) 1 by decreasing the de novo protein synthesis in ECs. Most importantly, we found that inhibition of importin-dependent NF-ĸB p65 nuclear translocation is a crucial part of the action of vioA leading to reduced NF-ĸB promotor activity and inflammatory gene expression. Knockdown experiments revealed a causal link between the cellular target NOP14 and the anti-inflammatory action of vioA, classifying the natural product as unique drug lead for anti-inflammatory therapeutics.
The natural product vioprolide A exerts anti-inflammatory actions through inhibition of its cellular target NOP14 and downregulation of importin-dependent NF-ĸB p65 nuclear translocation
https://www.sciencedirect.com/science/article/pii/S0753332221010398
As you may read, reduced NF-ĸB promotor activity and inflammatory gene expression and attenuation of the microglia and macrophage infiltration are very important in successfully treating COVID and Spike Protein related disease.
This has been looked at as a possible treatment in April of 2022.
A further target in the fight against COVID-19 is in microvascular phase, by limiting the tissue damage caused by activated leucocytes. However, this therapy is not microbe specific and effective in any vasculitis accelerated on the phagocyte pathway. Vioprolide A is a natural product isolated from the myxobacterium Cystobacter violaceus. It is a highly potent substance, showing promising effects on the vascular endothelium in inflammatory processes by reducing phagocyte–endothelial cell interactions and targeting the importin family of carrier proteins without exerting cytotoxic effects.
Adverse Cardiac Effects of SARS-CoV-2 Infection
https://www.japscjournal.com/articles/adverse-cardiac-effects-sars-cov-2-infection
In light of the recent findings, I believe Vioprolide A should be trialed and investigated by clinicians and research institutes. Vioprolide A may also be of great benefit to those suffering from Long COVID. Should any clinicians have tried this, please let me know the results.
Please have a blessed weekend. I will continue to work on our understanding of the Spike Protein and on therapeutics.
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Myocarditis Is Rare.
It's So Rare That Everyone Has It At Once.
See.
How Rare Is That?
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Great essay and heck yeah needs to be studied , thanks Walter https://pubmed.ncbi.nlm.nih.gov/34607110/