__This is not medical advice. Do not go out and take a bunch of losartan without a doctor, you could die.__
Here's the article's main point (from 2005): Kuba et al showed that by injecting losartan into mice (a common ACE inhibitor that is off patent) with a SARS-Coronavirus protein leads to less lung injury than the controls without losartan. No studies have shown this works in living, breathing humans, but...
(Oral) losartan is widely available (at least right now), it can be prescribed off-label by doctors and picked up today. As its on-label use is treating hypertension, obviously it will lead to low blood pressure, along with all the other possible side effects including life-threatening swelling and more. And since dehydration and sepsis can also lead to lower blood pressure, you'd be playing with fire in life-threatening ways without careful watch by a doctor. You can bet this is a source of ongoing research and trials, probably already underway.
__This is not medical advice. Do not go out and take a bunch of losartan without a doctor, you could die.__
This wasn’t in a petri dish actually, this was an in vivo study using mice. Other in vivo studies show similar.
There are actually no known trials with ARBs and SARS-CoV-2, which is really weird. There should be. One reason why is because most of the non-crazy (eg Chinese medicine) drugs being trailed were selected by semi-brute force from in vitro type testing. ARBs wouldn’t work in vitro AFAICT, which is a reason they haven’t been tested; the drug won’t stop the virus from entering cells the same way other drugs might, but instead may stop some or all of the major damage the virus does to the body.
There’s lots of discussion and papers collected here on this subject:
they would both have the effect of altering the state of the renin-angiotensin system
they work from different ends:
the receptor blocker, inhibits angiotensin II from binding
the ACE inhibitor, interferes with conversion of angiotensin I > angiotensin II ,,,,thus reducing the interaction between angiotensinII and the receptor.
In the case of ACE inhibitor the receptor is open and available for docking,,,in the case of the blocker, there is something that _may_ get in the way of viral peplomer docking to the receptor
ideally there exists, some sort of receptor blocker that competetively inhibits coronavirus peplomer binding but is also displaced by angiotensin II ,,, or binds in a site that does not interfere with the ligand recognition sites but prevents the binding of peplomer
They won’t block ACE2 but as indicated in the article they may prevent the lung damage associated with SARS by blocking AT1R which is the receptor that may mediate lung damage.
There’s lots of discussion and papers collected here:
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..
0. How can I find out if I have too high (?) ACE2, and what can I do about it? Are there symthoms at least?
1. What does modulating ACE means?
2. Do you mean shall everyone get those blood pressure meds? Or what is the relation now with these meds in terms of action? Does it mean people who need it must get it for sure?
3. Research what is needed to modulate ACE: can you please give a pointer.
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:
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.
One of the most popular blood pressure medications, Lisinopril, is an ACE inhibitor. A lot of people worldwide (including myself) take it daily. Its mechanism of action is to prevent the conversion of ACE to ACE2.
having high ACE2 is not something that you need to worry about as you only need enough to get the virus in you.
- having "high" ACE2 could actually be a benefit if it turns out that you retain proper ACE2 functionality after infection and through the course of the physiological challenge of the virus.
Readit News
Here's the article's main point (from 2005): Kuba et al showed that by injecting losartan into mice (a common ACE inhibitor that is off patent) with a SARS-Coronavirus protein leads to less lung injury than the controls without losartan. No studies have shown this works in living, breathing humans, but...
(Oral) losartan is widely available (at least right now), it can be prescribed off-label by doctors and picked up today. As its on-label use is treating hypertension, obviously it will lead to low blood pressure, along with all the other possible side effects including life-threatening swelling and more. And since dehydration and sepsis can also lead to lower blood pressure, you'd be playing with fire in life-threatening ways without careful watch by a doctor. You can bet this is a source of ongoing research and trials, probably already underway.
__This is not medical advice. Do not go out and take a bunch of losartan without a doctor, you could die.__
There are actually no known trials with ARBs and SARS-CoV-2, which is really weird. There should be. One reason why is because most of the non-crazy (eg Chinese medicine) drugs being trailed were selected by semi-brute force from in vitro type testing. ARBs wouldn’t work in vitro AFAICT, which is a reason they haven’t been tested; the drug won’t stop the virus from entering cells the same way other drugs might, but instead may stop some or all of the major damage the virus does to the body.
There’s lots of discussion and papers collected here on this subject:
https://twitter.com/__philipn__
https://en.wikipedia.org/wiki/Angiotensin_II_receptor_blocke...
they work from different ends:
the receptor blocker, inhibits angiotensin II from binding
the ACE inhibitor, interferes with conversion of angiotensin I > angiotensin II ,,,,thus reducing the interaction between angiotensinII and the receptor.
In the case of ACE inhibitor the receptor is open and available for docking,,,in the case of the blocker, there is something that _may_ get in the way of viral peplomer docking to the receptor
ideally there exists, some sort of receptor blocker that competetively inhibits coronavirus peplomer binding but is also displaced by angiotensin II ,,, or binds in a site that does not interfere with the ligand recognition sites but prevents the binding of peplomer
(Edit typo)
it's on bioarxiv, what exactly does 'too new' mean?
They will not block ACE2 which is a protein which gets expressed in the lung tissues.
Please Do not get carried away. https://en.wikipedia.org/wiki/Angiotensin-converting_enzyme_...
There’s lots of discussion and papers collected here:
https://twitter.com/__philipn__
But the research behind what is needed to modulate ACE is already there..
0. How can I find out if I have too high (?) ACE2, and what can I do about it? Are there symthoms at least?
1. What does modulating ACE means? 2. Do you mean shall everyone get those blood pressure meds? Or what is the relation now with these meds in terms of action? Does it mean people who need it must get it for sure? 3. Research what is needed to modulate ACE: can you please give a pointer.
It did make my prostate feel swollen for a couple days though.
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.
How can I find out if I have too high (?) ACE2, and what can I do about it? Are there sympthoms at least?
- having "high" ACE2 could actually be a benefit if it turns out that you retain proper ACE2 functionality after infection and through the course of the physiological challenge of the virus.
Scientific articles gain credibility as they age and no known exception to elucidated principles is apparent.
in this case the [2005] article is superior to a [2020] article.
i do agree however it is helpful and conventional to include a date of publication
Deleted Comment