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Posted On: 09/25/2020 5:20:42 AM
Post# of 145900
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Re: MD VIROLOGIST #57800
Quotes are from the linked paper.
Why the deterioration occurs is that Ang II increases RANTES (CCL5) production. Of course blocking the CCR5 binding site means CCL5 doesn't induce migration of macrophages to the site of Ang II.
CCR5 blockade disrupts the PI3K,mTOR / 4E-BP1 via downregulation of NF-kb. The same disrupted pathway I proposed for leronlimab's possible ability to act as a direct antiviral. CCR5 blockade also downregulates MAPK, ERK 1 and 2, JAK1 and 2, JNK (MAPK 8-10) and TNF-a.
I've shown in another post how CCR5 blockade downregulates bradykinin.
More complex than what they've outlined.
Quote:
Since angiotensin-(1–7) has a key counter-regulatory role in many of the angiotensin type 1 receptor (AT1R)-related physiopathological functions, the SARA-CoV-2-mediated downregulation of ACE2 and the resulting increased overall ratio of Ang II to angiotensin-(1–7) leads to the deterioration of the pulmonary function and lung injury
Why the deterioration occurs is that Ang II increases RANTES (CCL5) production. Of course blocking the CCR5 binding site means CCL5 doesn't induce migration of macrophages to the site of Ang II.
Quote:
Ang II can activate the nuclear factor kappa B (NF-κpathway [24], [25] via stimulation of the phosphorylation of the p65 subunit of NF-κB [26]. This will lead to increased production of IL-6 [27], TNFα, IL-1B and IL-10 [26]. After AT1R activation, Ang II regulates Mitogen-Activated Protein Kinases (MAPK) (ERK1/2, JNK, p38MAPK), which have important functions on cellular processes including the release of cytokines such as IL-1, IL-10, IL-12 and TNFα
CCR5 blockade disrupts the PI3K,mTOR / 4E-BP1 via downregulation of NF-kb. The same disrupted pathway I proposed for leronlimab's possible ability to act as a direct antiviral. CCR5 blockade also downregulates MAPK, ERK 1 and 2, JAK1 and 2, JNK (MAPK 8-10) and TNF-a.
Quote:
ACE2 /DABK/ bradykinin B1 receptor axis
I've shown in another post how CCR5 blockade downregulates bradykinin.
Quote:
Covid-19 cytokine storm is a complex network
More complex than what they've outlined.
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