Angiotensin converting enzyme 2 (ACE2) crucial in SARS-coronavirus lung injury (2005)
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Re: Angiotensin converting enzyme 2 (ACE2) crucial in SARS-coronavirus lung injury (2005)
#2That's a quite old (2005) article, dating to the original sars outbreak.
https://www.biorxiv.org/content/10.1101/2020.01.26.919985v1 is a much more recent one, specific to covid-19.
(Edit typo)
Re: Angiotensin converting enzyme 2 (ACE2) crucial in SARS-coronavirus lung injury (2005)
#3What are the implications of this?
Re: Angiotensin converting enzyme 2 (ACE2) crucial in SARS-coronavirus lung injury (2005)
#4What are the implications of this?
this is the mechanism a coronavirus assembly exploits to enter a cell.
the virion uses a peplomer [one of its spikes] to dock with the cell at the ACE2 receptor then wrenches it apart like cutting a door right out of its frame, then the virus inserts itself into the cell leaving its envelope and protien accessories fused with the cell membrane.
-if this mechanism can be blocked it will inhibit viral entry
-if it can be mimmicked a vaccine is possible
here is a good place to start looking at background information:
https://en.wikipedia.org/wiki/Renin%E2%80%93angiotensin_syst...
This is what is so damaging to the infected cells to begin with. it disrupts an essential signalling system.
Re: Angiotensin converting enzyme 2 (ACE2) crucial in SARS-coronavirus lung injury (2005)
#5That's a quite old (2005) article, dating to the original sars outbreak. https://www.biorxiv.org/content/10.1101/2020.01.26.919985v1 is a much more recent one, specific to covid-19. (Edit typo)
That particular preliminary linked to is too new and requires critical interpretation for a number of issues
Re: Angiotensin converting enzyme 2 (ACE2) crucial in SARS-coronavirus lung injury (2005)
#6What are the implications of this?
this is the mechanism a coronavirus assembly exploits to enter a cell. the virion uses a peplomer [one of its spikes] to dock with the cell at the ACE2 receptor then wrenches it apart like cutting a door right out of its frame, then the virus inserts itself into the cell leaving its envelope and protien accessories fused with the cell membrane. -if this mechanism can be blocked it will inhibit viral entry -if it can…
Another interesting side effect could be other temporizing measures in the inpatient setting. My understanding from a brief skim of older research papers is that the ACE inhibitors and angiotensin receptor blockers that we use today, like lisinopril or losartan, could upregulate the expression of ACE-2 receptors. If a patient is admitted with coronavirus, discontinuing blood pressure medications such as lisinopril and losartan could be worthwhile to decrease length of stay, morbidity, and mortality.
Re: Angiotensin converting enzyme 2 (ACE2) crucial in SARS-coronavirus lung injury (2005)
#7What are the implications of this?
the meds modulating ACE family of proteins are also commonly available as blood pressure meds, actually. But interestingly, the side effect is...coughing...
But the research behind what is needed to modulate ACE is already there..
Re: Angiotensin converting enzyme 2 (ACE2) crucial in SARS-coronavirus lung injury (2005)
#8Earlier quoted context omitted.
this is the mechanism a coronavirus assembly exploits to enter a cell. the virion uses a peplomer [one of its spikes] to dock with the cell at the ACE2 receptor then wrenches it apart like cutting a door right out of its frame, then the virus inserts itself into the cell leaving its envelope and protien accessories fused with the cell membrane. -if this mechanism can be blocked it will inhibit viral entry -if it can…
Another interesting side effect could be other temporizing measures in the inpatient setting. My understanding from a brief skim of older research papers is that the ACE inhibitors and angiotensin receptor blockers that we use today, like lisinopril or losartan, could upregulate the expression of ACE-2 receptors. If a patient is admitted with coronavirus, discontinuing blood pressure medications such as lisinopril an…
I suppose that explains why a lot (most?) of the people who died also suffered from high blood pressure.
Re: Angiotensin converting enzyme 2 (ACE2) crucial in SARS-coronavirus lung injury (2005)
#9Earlier quoted context omitted.
Another interesting side effect could be other temporizing measures in the inpatient setting. My understanding from a brief skim of older research papers is that the ACE inhibitors and angiotensin receptor blockers that we use today, like lisinopril or losartan, could upregulate the expression of ACE-2 receptors. If a patient is admitted with coronavirus, discontinuing blood pressure medications such as lisinopril an…
I suppose that explains why a lot (most?) of the people who died also suffered from high blood pressure.
No, I think that's just the fact that most of the people who died were older with lots of comorbidities, like high blood pressure, diabetes, COPD, etc
Re: Angiotensin converting enzyme 2 (ACE2) crucial in SARS-coronavirus lung injury (2005)
#10Earlier quoted context omitted.
this is the mechanism a coronavirus assembly exploits to enter a cell. the virion uses a peplomer [one of its spikes] to dock with the cell at the ACE2 receptor then wrenches it apart like cutting a door right out of its frame, then the virus inserts itself into the cell leaving its envelope and protien accessories fused with the cell membrane. -if this mechanism can be blocked it will inhibit viral entry -if it can…
Another interesting side effect could be other temporizing measures in the inpatient setting. My understanding from a brief skim of older research papers is that the ACE inhibitors and angiotensin receptor blockers that we use today, like lisinopril or losartan, could upregulate the expression of ACE-2 receptors. If a patient is admitted with coronavirus, discontinuing blood pressure medications such as lisinopril an…
this is something of a bush to beat around.
- when the virus docks with the ACE2 receptor there is a loss of the ACE2 receptor function as it is a destructive process.
- when the virus inhabits the cell there is probably a cytoplasmic down regulation of ACE2 expression as the cell is now "claimed" as a place for replication
so the question would be when would we administer or withdraw such an ACE2 blocker
the loss of ACE2 functionality is devastating to the cell but the presence of functional ACE2 receptor makes a cell vulnerable to entry
-and should we be using a blocker pe se or should we use some sort of hypothetical receptor inhibitor that is not displace by coronavirus spike protien, as in competetive inhibition?