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
Abstract :
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.
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.
