A few medicines of note here:
Ace inhibitors are a well known treatment that reduces blood pressure.
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:
Everyone is welcome to take their own health into their own hands. However, for others looking to this as advice, please be aware that:
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.
Jesus! Chloroquine has side effects like hearing damage, damage to the eye, irregular heart rhythm.
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.
Yeah, prepping is great but you might want to rethink this attitude.
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?
> I won't wait for docs to discuss prescribing it if i get any symptoms. I may even take it for preventative use.
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.
Where did you get Chloroquine from? It appears to be a semi-controlled substance, and most pharmacies won't sell it to you unless you can prove that you're traveling to one of the (very few) places left in the world where it's still an effective anti-malarial.
I also got chloroquine but I think I would use it on my parents or me only if we would be sick for a long time without ER room or something. What's your plan?
Consider me skeptical of the practical significance of their findings. IMO, protease inhibitors are a moot point if the they don't also block cell entry via antibody-dependent enhancement (ADE):
ADE has me worried the most. There's some circumstantial evidence that COVID-19 might use ADE. The arguments against it (from claimed medical experts) on reddit was basically "ADE is extremely rare."
If the evidence for/against something is based solely on percentages, you'll get a raised eyebrow from me.
ACE2 has direct effects on cardiac functiona and is expressed predominantly in vascular endothelial cells of the heart and the kidneys. -wikipedia
ACE2 entry is [betacoronavirus] lineage B clade 1 specific.
----- TMPRSS2 -----
• positive regulation of viral entry into host cell
• protein autoprocessing
• receptor-mediated endocytosis
• proteolysis
• vesicle-mediated transport
• endocytosis
This gene was demonstrated to be up-regulated by androgenic hormones in prostate cancer cells and down-regulated in androgen-independent prostate cancer tissue. The protease domain of this protein is thought to be cleaved and secreted into cell media after autocleavage. The biological function of this gene is unknown. - wikipedia
Interestingly, TMPRSS2 is the same exact pathway used by SARS, murine respirovirus and influenza. So, a blockade or modification of this might be a way to cure the flu as well.
TMPRSS2 entry is found in betacoronavirus lineage B, but not specific to it.
[+] [-] jamesblonde|6 years ago|reply
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
[+] [-] nkrumm|6 years ago|reply
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.
[1] e.g., https://www.ncbi.nlm.nih.gov/pubmed/15897343
[+] [-] refurb|6 years ago|reply
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.
[+] [-] forkexec|6 years ago|reply
https://www.drugs.com/sfx/chloroquine-side-effects.html
[+] [-] rscho|6 years ago|reply
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?
[+] [-] tom_mellior|6 years ago|reply
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?
[+] [-] rolph|6 years ago|reply
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.
[+] [-] jv22222|6 years ago|reply
“Expert consensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia”
https://www.ncbi.nlm.nih.gov/m/pubmed/32075365/
[+] [-] dTal|6 years ago|reply
[+] [-] biolurker1|6 years ago|reply
[+] [-] jmnicolas|6 years ago|reply
Sorry I don't remember much, but do some research before you use it.
[+] [-] romski|6 years ago|reply
[+] [-] d6e|6 years ago|reply
[+] [-] unknown|6 years ago|reply
[deleted]
[+] [-] campercoder|6 years ago|reply
[deleted]
[+] [-] DataDrivenMD|6 years ago|reply
- http://viruseradication.com/abstract-details.php?abstract_id...
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178114/
- https://jvi.asm.org/content/94/5/e02015-19.abstract
It's been a while since my vaccine research days at the NIH, so take my skepticism with a grain of salt.
[+] [-] snapetom|6 years ago|reply
If the evidence for/against something is based solely on percentages, you'll get a raised eyebrow from me.
[+] [-] forkexec|6 years ago|reply
what kind of cellular dysfunction would be caused by blockading ACE2 and TMPRSS2?
[+] [-] forkexec|6 years ago|reply
ACE2 entry is [betacoronavirus] lineage B clade 1 specific.
----- TMPRSS2 -----
• positive regulation of viral entry into host cell
• protein autoprocessing
• receptor-mediated endocytosis
• proteolysis
• vesicle-mediated transport
• endocytosis
This gene was demonstrated to be up-regulated by androgenic hormones in prostate cancer cells and down-regulated in androgen-independent prostate cancer tissue. The protease domain of this protein is thought to be cleaved and secreted into cell media after autocleavage. The biological function of this gene is unknown. - wikipedia
Interestingly, TMPRSS2 is the same exact pathway used by SARS, murine respirovirus and influenza. So, a blockade or modification of this might be a way to cure the flu as well.
TMPRSS2 entry is found in betacoronavirus lineage B, but not specific to it.
[+] [-] KaiserPro|6 years ago|reply
[+] [-] bittersourspicy|6 years ago|reply
Camostat
CAS: 59721-29-8
Approvals: Japan
$0.10/mg in bulk (2 week lead time), or $1.25/mg in-stock
https://en.wikipedia.org/wiki/Camostat
https://www.adooq.com/camostat-mesylate.html
https://www.medkoo.com/products/11665
----------
E-64d
CAS: 88321-09-9
LD50 in rats: >100000 mg/kg
$12.5/mg in-stock
https://www.sigmaaldrich.com/catalog/product/sigma/e8640
https://www.apexbt.com/e-64d.html
----------
Obviously: untested, unknown dosage and not FDA approved. It would need a little DMSO to dissolve both.
[+] [-] lm28469|6 years ago|reply