Angiotensin converting enzyme 2 (ACE2) crucial in SARS-coronavirus lung injury (2005) • Hacker News Board

Re: Angiotensin converting enzyme 2 (ACE2) crucial in SARS-coronavirus lung injury (2005)

#51

Post by koheripbal » Mon, Mar 02, 2020, 4:27 PM UTC

ptest1 wrote: post #45

rolph wrote: post #44

Earlier quoted context omitted.

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…

Just a little clarification. These renin-angiotensin terms are totally confusing (due to how similar they all are!) and from my correspondence with physicians, many of them even get them mixed up! Virus binds to and downregulates ACE2. ACE2 converts Ang II to Ang 1-7. Ang II binds to AT1R and AT2R receptors: https://twitter.com/__philipn__/status/1229607854232850432?s... Pic for clarity. When there’s less ACE2, and i…

So, to be clear, a patient should stop taking Losartan if he suspects he has covid-19, correct?

Re: Angiotensin converting enzyme 2 (ACE2) crucial in SARS-coronavirus lung injury (2005)

#52

Post by koheripbal » Mon, Mar 02, 2020, 4:28 PM UTC

rolph wrote: post #44

koheripbal wrote: post #43

Earlier quoted context omitted.

I'm confused. Losartan is a Angiotensin II receptor blocker (ARB). I thought that was different from an ACE inhibitor... https://en.wikipedia.org/wiki/Angiotensin_II_receptor_blocke...

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…

Ok, so then (assuming this all gets verified), then the recommendation for covid-19 patients taking Losartan, is that they stop taking it, correct?

Re: Angiotensin converting enzyme 2 (ACE2) crucial in SARS-coronavirus lung injury (2005)

#53

Post by rolph » Mon, Mar 02, 2020, 4:36 PM UTC

koheripbal wrote: post #51

ptest1 wrote: post #45

Earlier quoted context omitted.

Just a little clarification. These renin-angiotensin terms are totally confusing (due to how similar they all are!) and from my correspondence with physicians, many of them even get them mixed up! Virus binds to and downregulates ACE2. ACE2 converts Ang II to Ang 1-7. Ang II binds to AT1R and AT2R receptors: https://twitter.com/__philipn__/status/1229607854232850432?s... Pic for clarity. When there’s less ACE2, and i…

So, to be clear, a patient should stop taking Losartan if he suspects he has covid-19, correct?

you should stop taking losartan if directed to do so by your doctor.

this thread is descended from a conversation about recent discoveries and lead considerations that are not yet perfected and very probably not completely understood.

I get the idea that its tempting to try and find a physiological sweet spot where you can evade the virus,

but virus has a number of tools that work in concert to manipulate the host physiology into a working environment and exploit molecular machinery.

this ACE2 related pathology is likely multiprong so disruption of one aspect will not be sure to reduce harm.

on the flipside blood pressure modulators can be a problem with incorrect dosage. Your doctor has a better scoop on your health status then i could have in any short time so thats where you should ask about changing dosage, and getting some idea of just how much risk you might have if your exposed to the virus.

Re: Angiotensin converting enzyme 2 (ACE2) crucial in SARS-coronavirus lung injury (2005)

#54

Post by rolph » Mon, Mar 02, 2020, 5:22 PM UTC

koheripbal wrote: post #52

rolph wrote: post #44

Earlier quoted context omitted.

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…

Ok, so then (assuming this all gets verified), then the recommendation for covid-19 patients taking Losartan, is that they stop taking it, correct?

the TL:DR is dont stop your meds unless your doctor says so.

The gist of the thesis so far:

here is what we think is known so far.

ACE2 adjusts the amount of angiotensin II [given]

and when angiotensin II docks to its receptor [AT2] this results in a signal to increase your blood pressure.

this receptor [AT2] is where losartan does its job, it inhibits binding of angiotensin II to the AT2.

what the virus seems to do is dock with and disrupt the ACE2 protien, so your ability to adjust howmuch angiotensin II is free and available is disrupted.

what does this do? there is a lot more angiotensin II encountering the AT2 receptor, this causes blood pressure to go up, this causes the lungs to generate fibres between cells, this causes lung tissue to become less than optimum at being pliable elastic and permeable to gases.

This is not a good time to have a blood pressure spike. this is probably not a good time to do anything that increases the angiotensin II signal to the AT2 receptor.

your losartan _may_ actually help you.

now keep in mind this is ongoing way out to the very edge, preliminary research so dont do something risky like screwing around with these meds when this isnt even finished science.

Re: Angiotensin converting enzyme 2 (ACE2) crucial in SARS-coronavirus lung injury (2005)

#55

Post by koheripbal » Mon, Mar 02, 2020, 9:30 PM UTC

rolph wrote: post #54

koheripbal wrote: post #52

Earlier quoted context omitted.

Ok, so then (assuming this all gets verified), then the recommendation for covid-19 patients taking Losartan, is that they stop taking it, correct?

the TL:DR is dont stop your meds unless your doctor says so. The gist of the thesis so far: here is what we think is known so far. ACE2 adjusts the amount of angiotensin II [given] and when angiotensin II docks to its receptor [AT2] this results in a signal to increase your blood pressure. this receptor [AT2] is where losartan does its job, it inhibits binding of angiotensin II to the AT2. what the virus seems to do…

Ok, I see - so the ultimate recommendation may actually be to increase someone's losartan dosage.

Re: Angiotensin converting enzyme 2 (ACE2) crucial in SARS-coronavirus lung injury (2005)

#56

Post by koheripbal » Mon, Mar 02, 2020, 9:32 PM UTC

rolph wrote: post #53

koheripbal wrote: post #51

Earlier quoted context omitted.

So, to be clear, a patient should stop taking Losartan if he suspects he has covid-19, correct?

you should stop taking losartan if directed to do so by your doctor. this thread is descended from a conversation about recent discoveries and lead considerations that are not yet perfected and very probably not completely understood. I get the idea that its tempting to try and find a physiological sweet spot where you can evade the virus, but virus has a number of tools that work in concert to manipulate the host ph…

Although I suspect someone who's already taking Losartan and has a blood pressure increase due to covid19, a small increase in Losartan dosage is likely a low-risk effort that looks like it might be beneficial.

Re: Angiotensin converting enzyme 2 (ACE2) crucial in SARS-coronavirus lung injury (2005)

#57

Post by hcknwscommenter » Wed, Mar 04, 2020, 11:00 PM UTC

koheripbal wrote: post #56

rolph wrote: post #53

Earlier quoted context omitted.

you should stop taking losartan if directed to do so by your doctor. this thread is descended from a conversation about recent discoveries and lead considerations that are not yet perfected and very probably not completely understood. I get the idea that its tempting to try and find a physiological sweet spot where you can evade the virus, but virus has a number of tools that work in concert to manipulate the host ph…

Although I suspect someone who's already taking Losartan and has a blood pressure increase due to covid19, a small increase in Losartan dosage is likely a low-risk effort that looks like it might be beneficial.

increase Losartan dosage? beneficial? Highly unlikely.