The COVID-19 Code – Cracked – WHO can Save The World (?)!


Authors : Dr. Velmurugan Kuppuswamy; Dr. Deepa Nagarajan; Dr. Suhasini Balasubramaniam; Dr. Rajarajeswari Velmurugan; Dr. Safi Kottililkutty; Dr. (Lt. Commander) Devashish Tarra

Volume/Issue : Volume 5 - 2020, Issue 8 - August

Google Scholar : http://bitly.ws/9nMw

Scribd : https://bit.ly/33w5XN0

DOI : 10.38124/IJISRT20AUG276

The first step in COVID-19 pathogenesis is the viral spike protein priming by Trans Membrane Peptide Receptor Serine S2 (TMPRSS2). TMPRSS2 promotes viral entry, cell to cell transmission, evasion of host immune response, and Angiotensin-Converting Enzyme 2 (ACE2) downregulation. Androgen through Androgen Receptor (AR) increases TMPRSS2 gene expression. Blocking AR may prevent viral entry and other TMPRSS2 mediated actions. ACE2 acts as an entry point for COVID-19 and as the counter regulator in Renin-Angiotensin-Aldosterone System (RAAS). RAAS maintains homeostasis of blood pressure, salt and water, inflammation, and immune response – through its two arms called “killer” and “protective pathways.” The balance between these two pathways determines life or death in disease states. ACE2 converts Angiotensin II to Angiotensin (1-7), which through Mas receptors mediates antiinflammatory, immune-modulatory, and anti-fibrotic actions. Angiotensin II also acts on Angiotensin type 2 Receptor (AT2R) to produce similar actions, called a "protective pathway." Further, Angiotensin II acts through its primary Angiotensin type 1 Receptor (AT1R), causing inflammatory, cytokine storm, and profibrotic response – called "Killer pathway." In COVID, down-regulated ACE2 leads to unabated Angiotensin II/AT1R – "Killer pathway" – actions producing a vicious cycle of "hyper-inflammatory state," resulting in ALI, ARDS, and death. AT1R activation further stimulates the secretion of aldosterone, which through Mineralocorticoid Receptor (MR), augments AT1R mediated 'killer pathway”. None of the COVID guideline drugs modulate this pathogenic mechanism. We examine the first time in history the scientific rationale for combined AR/AT1R/MR blockade for COVID-19 treatment and prevention.

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