4 ms·

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 e

__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 7y ago
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 7y ago
  Thanks, corrected my comment. I'd also expect observational studies since ace-inhibitors are so widespread.
koheripbal 7y ago
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_blocker https://en.wikipedia.org/wiki/Angiotensin_II_receptor_blocke...
- rolph 7y ago
  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
  - ptest1 7y ago
    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=21 https://twitter.com/__philipn__/status/1229607854232850432?s... Pic for clarity. When there’s less ACE2, and in general due to immune response, there will be more Ang II to bind to AT1R. This AT1R binding may create the lung injury seen with the virus. The idea is that by blocking AT1R with an ARB type drug you don’t stop the virus from entering a cell, but you instead stop the body’s pathological response to the virus. After all, most viruses don’t kill us, and our immune system - if it doesn’t over react - will usually kill a thing if it has enough time and the virus isn’t “special” like HIV or herpes (that’s my general, non expert understanding!) While it seems smart to try and inhibit ACE2 directly, there are a couple problems with this I see: 1. It may be pathological. More Ang II to bind to AT1R, you might end up way worse off. ACE2 is the “good” ACE, and all the evidence we have seems to suggest that a reduction in the ACE2:ACE ratio will make tissue fibrosis, death, etc worse. This happens in the heart and lungs in mouse models. 2. Small molecule ACE2 inhibitors bind to the C shaped area of the ACE2 enzyme, while the virus attaches to the back. So they likely may not inhibit cell entry: https://twitter.com/robertlkruse/status/1230577662751641601?s=21 https://twitter.com/robertlkruse/status/1230577662751641601?... The best silver bullet bet here is ACE2-fc, which isn’t a small molecule. This is a soluble form of the ACE2 protein along with an fc. this gives it a longer half life in the body. This would likely: 1. Stop virus cell entry by neutralizing the virus- virus binds to ACE2-fc instead of the cell ACE2. 2. Stop potential lung damage from AT1R activation. Both 1 and 2 have been shown in some models. It is now being tested in vitro. Next animals. Chinese are testing non-fc form, ACE2 directly, but requires IV drip. Testing now directly in humans! 7 day trial. See twitter for more on this: https://twitter.com/__philipn__ https://twitter.com/__philipn__ If you’re a funder, VC and you’re reading this: The scientist at John Hopkins who’s developing ACE2-fc is looking for funding. He’s working with Chinese biotech firms now to do the testing. Please comment here and I will connect you.

__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 e

ptest1 7y ago

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 7y ago
Thanks, corrected my comment. I'd also expect observational studies since ace-inhibitors are so widespread.

koheripbal 7y ago

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_blocker https://en.wikipedia.org/wiki/Angiotensin_II_receptor_blocke...

rolph 7y ago
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
- ptest1 7y ago
  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=21 https://twitter.com/__philipn__/status/1229607854232850432?s... Pic for clarity. When there’s less ACE2, and in general due to immune response, there will be more Ang II to bind to AT1R. This AT1R binding may create the lung injury seen with the virus. The idea is that by blocking AT1R with an ARB type drug you don’t stop the virus from entering a cell, but you instead stop the body’s pathological response to the virus. After all, most viruses don’t kill us, and our immune system - if it doesn’t over react - will usually kill a thing if it has enough time and the virus isn’t “special” like HIV or herpes (that’s my general, non expert understanding!) While it seems smart to try and inhibit ACE2 directly, there are a couple problems with this I see: 1. It may be pathological. More Ang II to bind to AT1R, you might end up way worse off. ACE2 is the “good” ACE, and all the evidence we have seems to suggest that a reduction in the ACE2:ACE ratio will make tissue fibrosis, death, etc worse. This happens in the heart and lungs in mouse models. 2. Small molecule ACE2 inhibitors bind to the C shaped area of the ACE2 enzyme, while the virus attaches to the back. So they likely may not inhibit cell entry: https://twitter.com/robertlkruse/status/1230577662751641601?s=21 https://twitter.com/robertlkruse/status/1230577662751641601?... The best silver bullet bet here is ACE2-fc, which isn’t a small molecule. This is a soluble form of the ACE2 protein along with an fc. this gives it a longer half life in the body. This would likely: 1. Stop virus cell entry by neutralizing the virus- virus binds to ACE2-fc instead of the cell ACE2. 2. Stop potential lung damage from AT1R activation. Both 1 and 2 have been shown in some models. It is now being tested in vitro. Next animals. Chinese are testing non-fc form, ACE2 directly, but requires IV drip. Testing now directly in humans! 7 day trial. See twitter for more on this: https://twitter.com/__philipn__ https://twitter.com/__philipn__ If you’re a funder, VC and you’re reading this: The scientist at John Hopkins who’s developing ACE2-fc is looking for funding. He’s working with Chinese biotech firms now to do the testing. Please comment here and I will connect you.