
Angiotensin converting enzyme 2 (ACE2) crucial in SARS-coronavirus lung injury (2005) - Khelavaster
https://www.nature.com/articles/nm1267?v=1
======
CapriciousCptl
__ __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. ____

~~~
ptest1
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:

[https://twitter.com/__philipn__](https://twitter.com/__philipn__)

~~~
CapriciousCptl
Thanks, corrected my comment. I'd also expect observational studies since ace-
inhibitors are so widespread.

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anonobviosly
That's a quite old (2005) article, dating to the original sars outbreak.
[https://www.biorxiv.org/content/10.1101/2020.01.26.919985v1](https://www.biorxiv.org/content/10.1101/2020.01.26.919985v1)
is a much more recent one, specific to covid-19.

(Edit typo)

~~~
rolph
That particular preliminary linked to is too new and requires critical
interpretation for a number of issues

~~~
dnautics
> is too new

it's on bioarxiv, what exactly does 'too new' mean?

~~~
rolph
a preliminary submission has not passed a peer review with the rigor of
scientific defense.

these sorts of things may be passed among researchers for extended periods of
time [years] until all the kinks are worked out of the thesis and a working
theory with no known exceptions and independently confirmed agreement of
results occurs.

jan 26 2020 is the submission date.

~~~
dnautics
What exactly is the standard of peer review you're expecting? Unless you have
reason to think they flat out fabricated the data, the analysis is probably no
better or worse than your garden variety nature or science or cell paper.

------
noipv4
ARB stands for AT1R blockers ( angiotensin II type one ) and they represent a
major class of antihypertensive medications. These drugs end in sartan.

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_...](https://en.wikipedia.org/wiki/Angiotensin-
converting_enzyme_2)

~~~
ptest1
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:

[https://twitter.com/__philipn__](https://twitter.com/__philipn__)

------
jfries
What are the implications of this?

~~~
caycep
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..

~~~
pezo1919
Sorry I don't know much about the topic.

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.

~~~
rolph
have a look here ;

[https://news.ycombinator.com/item?id=22458302](https://news.ycombinator.com/item?id=22458302)

~~~
pezo1919
Thanks a lot

------
m0zg
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.

~~~
unsrsly
Lisinopril is a competitive inhibitor of ACE that prevents it from converting
Angiotensin I to Angiotensin II

------
pezo1919
How can I find it out if I have high ACE2?

~~~
rolph
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.

~~~
seieste
This seems to be in contradiction of other published results. Can you provide
a source?

~~~
ptest1
As far as I can tell, there are no studies showing a higher ACE2 causes more
severe disease. Sure, it could, but the pathophysiological models and animal
data suggest that it is the _loss_ of ACE2 that may drive disease severity.

There is a contradictory preprint (that hasn’t passed peer review) on ACE2
mRNA expression in smokers’ lungs being higher than non-smokers; but there is
data saying the opposite happens in animal models of mice exposed to smoke:

[https://pubmed.ncbi.nlm.nih.gov/20178811-losartan-
attenuates...](https://pubmed.ncbi.nlm.nih.gov/20178811-losartan-attenuates-
chronic-cigarette-smoke-exposure-induced-pulmonary-arterial-hypertension-in-
rats-possible-involvement-of-angiotensin-converting-enzyme-2/)

There is also an inaccurate preprint on ethnic groups and ACE2 expression with
a low n count which also didn’t pass peer review.

ACE2 loss is probably bad, having more ACE2 probably doesn’t drive disease
severity:

[https://twitter.com/__philipn__/status/1229568317167243264?s...](https://twitter.com/__philipn__/status/1229568317167243264?s=21)

Relative ace2 reduction correlates w disease severity; viral load growth the
same between groups - check out study! Chinese paper discusses this as well:

[https://pubmed.ncbi.nlm.nih.gov/32061198-inhibitors-of-
ras-m...](https://pubmed.ncbi.nlm.nih.gov/32061198-inhibitors-of-ras-might-be-
a-good-choice-for-the-therapy-of-
covid-19-pneumonia/?from_single_result=Inhibitors+of+RAS+covid)

------
_bxg1
Can we get a (2005)?

~~~
rolph
there is a difference between tech and science with regard to correlations
between recency and quality.

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

~~~
_bxg1
People reading quickly might mistake it for being about the current
Coronavirus. The date would help rule that out.

~~~
rolph
for all intents and purposes it is about the current coronavirus. regardless
of drift the viral peplomer is still being used to dock with the ACE2 receptor
protien and still uses a small sequence region to bind the receptor.

