January 8, 2022
I believe the endocytosis of the Spike Protein is interfering with Ryanodine Receptors causing a calcium channelopathy resulting in Catecholaminergic Polymorphic Ventricular Tachycardia. This is a potentially fatal arrhythmia which is induced when the heart rate exceeds 120 bpm.
The intracellular actions of the Spike Protein with Cathepsin L, a protease on the plasma membrane of host cells, increases Ca2+ release from the endoplasmic reticulum (ER) via the ryanodine receptors (RyRs). The associated elevation of cytosolic Ca2+ concentration, in turn, increases cathepsin L activity. Cathepsin L promotes virus fusion with host cells by cleaving and activating the spike (S) protein. High levels of extracellular and cytosolic Ca2+ concentrations are also necessary for virus fusion and endocytosis. Cathepsin L in the endosome, under the condition of a high level of Ca2+ concentration, promotes virus RNA release into the cytosol. On the other hand, the increased cytosolic Ca2+ concentration due to the overactivation of RyRs activates calcineurin, which dephosphorylates NF-AT and translocates into the nucleus for promoting transcription and virus replication. Excess Ca2+ release from ER via overactivation of RyRs in AD cells results in depletion of ER Ca2+ and associated ER stress, as well as the overloading of mitochondria with Ca2+ and associated mitochondria damage.
The Spike Protein therapies should be paused while this mechanism is investigated.
Referenced/Related Papers
Ryanodine receptor channelopathies
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC2885589/
Channelopathies as Causes of Sudden Cardiac Death
https://pubmed.ncbi.nlm.nih.gov/29173400/
SARS-CoV-2 infects cells after viral entry via clathrin-mediated endocytosis
https://www.jbc.org/article/S0021-9258(21)00075-2/fulltext
Endocytosis of the receptor-binding domain of SARS-CoV spike protein together with virus receptor ACE2
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7114441/
Could dantrolene be explored as a repurposed drug to treat COVID-19 patients by restoring intracellular calcium homeostasis?