1) ACE inhibitors (lisinopril, etc.) are generally though to be enzymatic inhibitors of ACE, not ACE2 [1]. Also, enzymatic inhibition of the enzyme does not mean that it will prevent a virus from using that protein as an entry mechanism.
2) Chloroquine is an old drug with a well known safety profile, but it is certainly not a "safe" drug-- there are many known side effects including life threatening or severely disabling ones. As an MD, I recommend always consulting with your own medical provider(s) before starting any medications.
Correct. Ace inhibitors have shown no effect on ACE2.
https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1440-1681....
https://www.ncbi.nlm.nih.gov/pubmed/15897343
In addition there is also this specific recent Covid19 paper which does cautiously attract attention on this matter.
https://www.nature.com/articles/s41569-020-0360-5
I had a talk with 2 cardiologists and their response (this is not medical advice, talk to your cardiologist) was that it would be reasonable at least until further research is completed to for instance switch medication from ACE inhibitors to a Calcium Channel Blocker (such as Lercanidipine). At least until the pandemic gets under control and/or vaccine/treatment is available and validated.
There are very few cons to this safety measure if this can prevent complications. But that's my sole opinion and again, not medical advice. This might be worth at least an inquiry to your cardiologist. Especially if you're over 60.
(Sorry for by bad English, not a native speaker)
However, your first two papers seem to state ACE inhibitors makes ACE2 worse in terms of COVID-19.
"Losartan increased plasma levels of both Ang II and Ang-(1-7), as well as cardiac ACE2 mRNA and cardiac ACE2 activity"
The last one does nothing except say, "someone should look at it."
this does not mean the ACE2 enzyme activity or concentration is increased
"Selective blockade of either Ang II synthesis or activity induced increases in cardiac ACE2 gene expression and cardiac ACE2 activity, whereas the combination of losartan and lisinopril was associated with elevated cardiac ACE2 activity"
should I check in with my cardiologist?
This is only just starting to see clinical trials, meaning the people involved are under direct physician supervision.
regarding ACE2:
this increased production of ACE2 is an indirect effect of ACE2 disruption.
you have to be careful with these sorts of experiments. when you block angiotensin II receptors that means there is a reduction of signal for angiotensin II being present.
This angiotensin that would ordinarily be interacting with the ATreceptors is now available for ACE2 to operate upon.
the summary here is that increased enzymatic product doesnt mean the enzyme has been "turbocharged" . If there is an increased ratio of reactants to products this will cause increased concentration of products in total but does not change the intrinsic rate at which the enzyme actually operates.
This looks like a case of substrate concentration dependent equilibrium driving reaction rate.
these have opposite effects , angiotensin II is a vaso-constrictor, thus increases blood pressure.
angoitensin 1,7 is a vaso-dialator, thus decreases blood pressure. so there is an equilibrium state of the two established by ACE2. this is something that ACE inhibitors or ARB blockers dont directly influence.
Since when? Last time I checked my body my choice does not apply to the vast majority of pharmaceuticals unless a third party approves it.
But go ahead, see a witch doctor and a herbalist and take some random medication you read about in the internet.
It’s a terribly dirty drug.
This medicine may cause heart problems and changes in your heart rhythm. Check with your doctor right away if you have chest pain or tightness, decreased urine output, dilated neck veins, extreme fatigue, swelling of the face, fingers, feet, or lower legs, troubled breathing, or weight gain. You may also feel dizzy or faint, or you may have a fast, pounding, or uneven heartbeat.
This medicine may cause hypoglycemia (low blood sugar), which may be life-threatening. Low blood sugar must be treated before it causes you to pass out (unconsciousness). People feel different symptoms of low blood sugar. It is important that you learn which symptoms you usually have so you can treat it quickly. Talk to your doctor about the best way to treat low blood sugar.
Chloroquine may cause vision problems. It may also make you dizzy or lightheaded. Do not drive or do anything else that could be dangerous until you know how this medicine affects you. . If these reactions are especially bothersome, check with your doctor.
Check with your doctor immediately if blurred vision, difficulty with reading, or any other change in vision occurs during or after treatment. Your doctor may want your eyes be checked by an ophthalmologist (eye doctor).
This medicine may cause extrapyramidal disorders (eg, dystonia, dyskinesia, tongue protrusion, torticollis). Check with your doctor right away if you have the following symptoms after using the medicine: difficulty in speaking, drooling, loss of balance control, muscle trembling, jerking, or stiffness, restlessness, shuffling walk, stiffness of the limbs, twisting movements of the body, or uncontrolled movements, especially of the face, neck, and back.
Truth is, we don't know what works and you must realize that many (most?) people publishing in those papers you read don't have your well-being as their first priority.
You defy docs who prescribe, but why not also defy those who attempt to ride the fear wave to publish?
In addition to what everyone else said, would this even make sense in non-preventative use? By the time you show symptoms, the virus has already had several days to spread around your body. Would disrupting cell entry not be much too late at that point?
protease inhibitors are a major part of what was being demonstrated here.
the spike protien docks with the human ACE2 enzyme, that is for certain. this is only one part of the entry process.
after docking the spike protien must be "cut loose" [primed] in order to allow the membrane fusion process to proceed. this cutting occurs at the behest of exocytic serine protease, named [TMPRSS2].
the function of TMPRSS2 is not very clear but it seems to facilitate viral entry of SARS-2, Thus serine protease interaction must be manipulated in addition to interfering with ACE2 docking.
Then there is the damage. ACE2 sweeps up angiotensins I, and II and converts them into a nonactive form thus regulating the angiotensin pool created by ACE.
when angiotensin II reaches its receptor [ATR] the immediate functional effect is to cause vasoconstriction and increase blood pressure to operational level.
when ACE2 is disrupted from managing the angiotensin II pool there is an excess of ATR activation and this leads to a pathological state. The space between lung epithelial cells becomes reinforced with extracellular fibres leading to pulmonary sclerosis in addition to widespread cell death in lung tissue.
this is where the concept of ACE inhibitor and ATR blockers come into play. the reduction of angiotensinII and reduction of ATR signalling is thought to be a method of mediating this pathophysiological consequence of initial ACE2 disruption during viral docking process.
the whole picture is to block the virus ability to dock, and block virus ability to initiate the fusion process; And to mediate damages caused by the disruption of the RAS by way of ACE inhibitors and ATR blocking.
that means four points of leverege in this system, require four drugs minimum and clinical care for patient management.
“Expert consensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia”
(Doxycycline and other antimalarials are also terrible, just better than getting malaria.)
This can change your mind
Sorry I don't remember much, but do some research before you use it.
Right now on this day, OP is probably more likely to die from chloroquine administration than from the pandemic.
You are statistically comparing oranges to apples. This behaviour increases your risk of hurting yourself by a large margin compared to simply following WHO recommendations.
On another note, this is a nice thread helping me (and maybe others) inform them about side effects and efficacy of possible treatments.
Even if it works, and isn't just wishful thinking / propaganda.
> Side-effects
> Rare or very rare
> Cardiomyopathy; hallucination; hepatitis
>Frequency not known
> Abdominal pain; agranulocytosis; alopecia; anxiety; atrioventricular block; bone marrow disorders; confusion; corneal deposits; depression; diarrhoea; eye disorders; gastrointestinal disorder; headache; hearing impairment; hypoglycaemia; hypotension; insomnia; interstitial lung disease; movement disorders; myopathy; nausea; neuromyopathy; neutropenia; personality change; photosensitivity reaction; psychotic disorder; QT interval prolongation; seizure; severe cutaneous adverse reactions (SCARs); skin reactions; thrombocytopenia; tinnitus; tongue protrusion; vision disorders; vomiting
This "frequency not known" is listed alphabetically. There's some potentially fatal things in that list.
However, there are two different types of medicine undergoing clinical trials: Lopinavir/Ritonavir (tradename KALETRA) - a HIV medicine has shown promise and chloroquine - a 60+ year old anti-malaria medicine
Personally, i ordered chloroquine - well known safety profile. I won't wait for docs to discuss prescribing it if i get any symptoms. I may even take it for preventative use. I also have sequenced my DNA (full genome), and checked if I have any mutations that are know to increase production of ACE2 - increasing susceptibility to acquiring covid-19:
https://www.nature.com/articles/s41421-020-0147-1