The following is what Brazilian researchers came up with when studying tadpoles. On the one hand, the protein fragments that make up the spike proteins increased oxidative stress, and on the other hand, they increased the activity of the so-called acetylcholinesterase, thereby excessively degrading acetylcholine from the nervous system and other cells. (1) The latter has serious consequences. If the acetylcholine in the heart decreases, its effects are permanently damaging to the heart and it can promote the development of heart failure. This may be indicated by an increase in heart rate, which is also quite common in Covid patients with mild symptoms. Decreased acetylcholine in the heart may be accompanied by the weakening of the parasympathetic nervous system and a jump in heart rate. (2) (3) Decreased acetylcholine and damage to the acetylcholine signaling system also have serious consequences in the central nervous system. It reduces the function of the neural inflammatory pathway, the cholinergic anti-inflammatory pathway, and promotes the development of a cytokine storm and the development of a life-threatening condition. (4) In those with pre-existing brain damage to the acetylcholine signaling system, such as at patients with Alzheimer’s, impaired heart rate variability also indicates dysfunction of the anti-inflammatory cholinergic system and thus the coronavirus caused disease is more prone to the development of cytokine storms. (5) Scientists, therefore, recommend activating the vagus nerve and strengthening the cholinergic anti-inflammatory pathway in the fight against coronavirus. (6) (7) It has a good reason that the infection becomes critical and a cytokine storm occurs in those who have previously shown a significant drop in heart rate variability (HRV), as this predicts a weakening of the cholinergic anti-inflammatory pathway. (8)
In my opinion, it is shocking that, as a primary drug defense against coronavirus, immunization therapies based on the toxic proteins of spike protein are being introduced and injected into the bloodstream. This is certainly based on a disregard for the existing spike protein literature. The neurotoxic effect of spike protein may be significantly enhanced by the possible aluminum content of vaccines, such as for EpiVacCorona rated as 100% effective. (13) The use of proinsulin c-peptide may be a promising therapeutic intervention for several reasons. On the one hand, it can generally reduce oxidative stress. (9) (10) (11) On the other hand, it can effectively strengthen HRV and thus the cholinergic anti-inflammatory pathway. (12)
(1) Ives Charlie-Silva, Amanda P. C. Araújo, Abraão T. B. Guimarães, Flávio P Veras, Helyson L. B. Braz, Letícia G. de Pontes, Roberta J. B. Jorge, Marco A. A. Belo, Bianca H V. Fernandes, View ORCID ProfileRafael H. Nóbrega, Giovane Galdino, Antônio Condino-Neto, Jorge Galindo-Villegas, Glaucia M. Machado-Santelli, Paulo R. S. Sanches, Rafael M. Rezende, Eduardo M. Cilli, Guilherme Malafaia
An insight into neurotoxic and toxicity of spike fragments SARS-CoV-2 by exposure environment: A threat to aquatic health? https://www.biorxiv.org/…/10.1101/2021.01.11.425914v1.full
(2) Roy A, Dakroub M, Tezini GC, et al. Cardiac acetylcholine inhibits ventricular remodeling and dysfunction under pathologic conditions. FASEB J. 2016;30(2):688-701. doi:10.1096/fj.15-277046 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6188225/
(3) Roy A, Fields WC, Rocha-Resende C, et al. Cardiomyocyte-secreted acetylcholine is required for maintenance of homeostasis in the heart. FASEB J. 2013;27(12):5072-5082. doi:10.1096/fj.13-238279 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3834786/
(4) Lehner KR, Silverman HA, Addorisio ME, et al. Forebrain Cholinergic Signaling Regulates Innate Immune Responses and Inflammation. Front Immunol. 2019;10:585. Published 2019 Apr 2. doi:10.3389/fimmu.2019.00585 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6455130/
(5) Pomara N, Imbimbo BP. Impairment of the cholinergic anti-inflammatory pathway in older subjects with severe COVID-19. Med Hypotheses. 2020;144:110274. doi:10.1016/j.mehy.2020.110274 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493726/
(6) Bonaz B, Sinniger V, Pellissier S. Targeting the cholinergic anti-inflammatory pathway with vagus nerve stimulation in patients with Covid-19? Bioelectron Med. 2020 Jul 29;6:15. doi: 10.1186/s42234-020-00051-7. PMID: 32743022; PMCID: PMC7387121. https://pubmed.ncbi.nlm.nih.gov/32743022/
(7) Mazloom R. Feasibility of Therapeutic Effects of the Cholinergic Anti-Inflammatory Pathway on COVID-19 Symptoms. J Neuroimmune Pharmacol. 2020;15(2):165-166. doi:10.1007/s11481-020-09919-6 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202901/
(8) Frederick Hasty, MD, Guillermo García, MD, Col Héctor Dávila, MD, MSS, MC, USAR (Ret.), S Howard Wittels, MD, Stephanie Hendricks, BA, Stephanie Chong, DNP, CRNA, ARNP, Heart Rate Variability as a Possible Predictive Marker for Acute Inflammatory Response in COVID-19 Patients, Military Medicine, 2020;, usaa405, https://doi.org/10.1093/milmed/usaa405
(9) Essid SM, Bevington A, Brunskill NJ. Proinsulin C-Peptide Enhances Cell Survival and Protects against Simvastatin-Induced Myotoxicity in L6 Rat Myoblasts. Int J Mol Sci. 2019;20(7):1654. Published 2019 Apr 3. doi:10.3390/ijms20071654 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6479794/
(10) Cifarelli V, Geng X, Styche A, Lakomy R, Trucco M, Luppi P. C-peptide reduces high-glucose-induced apoptosis of endothelial cells and decreases NAD(P)H-oxidase reactive oxygen species generation in human aortic endothelial cells. Diabetologia. 2011 Oct;54(10):2702-12. doi: 10.1007/s00125-011-2251-0. Epub 2011 Jul 20. PMID: 21773684. https://pubmed.ncbi.nlm.nih.gov/21773684/
(11) Bhatt MP, Lim YC, Hwang J, Na S, Kim YM, Ha KS. C-peptide prevents hyperglycemia-induced endothelial apoptosis through inhibition of reactive oxygen species-mediated transglutaminase 2 activation. Diabetes. 2013;62(1):243-253. doi:10.2337/db12-0293 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3526059/
(12) Johansson BL, Borg K, Fernqvist-Forbes E, Odergren T, Remahl S, Wahren J. C-peptide improves autonomic nerve function in IDDM patients. Diabetologia. 1996 Jun;39(6):687-95. doi: 10.1007/BF00418540. PMID: 8781764. https://pubmed.ncbi.nlm.nih.gov/8781764/
(13) https://clinicaltrials.gov/ct2/show/NCT04527575
S protein is the primary target to produce vaccines 148 against COVID-19, as reported in different studies.
These data are exciting since they corroborate previous studies that describe the critical role the SARS-CoV-2 Spike protein in inducing oxidative stress in COVID-19 infection [see the review of Suhail et al. (2020)] while demonstrating that the peptides evaluated, even in a non-host organism, can cause metabolic disorders related to the increase in reactive species.
the increase in antioxidant defenses does not seem to have been sufficient to reduce oxidative stress, at a concentration of 500 ng/mL, all the peptides evaluated exerted an effect in the cholinergic system, causing an increase in the activity of AChE (Figure 7) While the peptides PSPD2001 and PSPD2002 induced increases of 219 and 553.8% in relation to AChE activity in the control group’s animals, respectively; the PSPD2003 peptide impressively induced an even more significant increase (697.3%). Therefore, these data confirmed the initial hypothesis that the SARS-CoV-2 Spike fragments induce neurotoxic effects, inferred by the stimulatory effect of the cholinergic system of the animals evaluated, especially in those exposed to the highest concentration (500 ng/mL) of the peptides.