Correct I understand. Any accounting for genetic differences relative to thiss gateway? How do ACE2 inhibitors work and do they show any promise on this?
Thanks for any correction and contradiction.
ACE inhibitors (e.g., lisinopril) are used to regulate hypertension. I need to look this stuff up and then be able to say it in plain English, and I’ll get back to you unless someone else here can explain it as easily as falling out of bed. (My knowledge base is old and rusty.)
“A recent letter to The Lancet has noted that comorbidities reported so far for severe coronavirus patients include hypertension and either type I or type II diabetes. These patients are often being treated with ACE-1 inhibitors or angiotensin-receptor antagonists. The tricky part is that both diabetes itself and treatment with either of those drug classes increases the expression of ACE-2 protein. At first thought, that would probably not be a good thing, loading up the cells with more viral target proteins. But wait: there’s another effect, as noted in this new paper. It builds on reports from China to suggest that a mechanism of lung injury during the viral infection may be through inappropriate effects of excess free angiotensin-II protein, which is floating around out there because the ACE-2 that would normally be soaking it up is occupied by coronavirus particles. If that’s the problem, then increasing the amount of ACE-2 protein might paradoxically be just what you want to do to restore some balance to the angiotensin system. In that case administering more angiotensin receptor antagonists would be an effective way to upregulate the production of ACE-2. That second paper proposes sorting through the existing patient data to see if there are correlations between severity of infection and angiotensin receptor antagonist therapy in particular, and I believe that this is ongoing. Epithelial cells are going to have ACE-2 protein on their surfaces no matter what, so the virus is going to be attacking those as a route of entry. If that second paper is right, then it could be that throwing more ACE-2 onto those membrane doesn’t make the viral infection much worse, but does lessen the associated lung injury. If we’re going to have a lot more coronavirus patients, this would be a very good thing to know.” https://blogs.sciencemag.org/pipeline/archives/2020/03/17/angiotensin-and-the-coronavirus
“...according to studies conducted on mice, the interaction of the spike protein of the coronavirus with ACE2 induces a drop in the levels of ACE2 in cells through internalization and degradation of the protein and hence may contribute to lung damage.” "Both ACE inhibitors and angiotensin receptor blockers (ARBs) that are used to treat high blood pressure have been shown in rodent studies to upregulate ACE2 expression hence may affect the severity of coronavirus infections.[28][29] However, multiple regulatory bodies have recommended continuing standard ACE inhibitor and ARB therapy.[30] A systematic review and meta-analysis found that "use of ACE inhibitors was associated with a significant 34% reduction in risk of pneumonia compared with controls." and 'The risk of pneumonia was also reduced in patients treated with ACE inhibitors who were at higher risk of pneumonia, in particular those with stroke and heart failure. Use of ACE inhibitors was also associated with a reduction in pneumonia related mortality, although the results were less robust than for overall risk of pneumonia.' “ https://en.wikipedia.org/wiki/Angiotensin-converting_enzyme_2
RummyChick, have you read about any other genetic susceptibilities?