3083 replies to this topic

[Daniel Cooper]

Vaping something with nicotine might be beneficial without some of the downsides of smoking.  There are enough people vaping out there it would be interesting to see if there is any correlation to hospitalization rates.  You'd have to control that for age as most vapers are younger than the average smoker.

 

If you wanted it to look like a genuine medical procedure I suppose you could put a nicotine solution in one of these over the counter nebulizers. 

 

  

[Izan]

More on the smoking paradox...  

 

https://www.dailymai...oronavirus.html

 

Professor Francois Balloux, director of the genetics institute at University College London: "the evidence for a protective effect of smoking (or nicotine) against COVID-19 is bizarrely strong... actually far stronger than for any drug trialed at this stage"

 

Far stronger than for any drug trialed at this stage???  WTF!

 

"America's Centers for Disease Control of over 7,000 people who tested positive for coronavirus, found that just 1.3 per cent of them were smokers - against the 14 percent of all Americans that the CDC says smoke"

 

"Hospitals in China, the US, Germany and France have had hundreds of thousands of coronavirus patients but admitted disproportionately small numbers of smokers"

 

"Data from the Centers for Disease Control and Prevention (CDC) in the US showed that of around 7,000 COVID-19 patients, former smokers were more likely to be hospitalized or taken into intensive care than current smokers"

 

--------------------------

 

The ACE2 issue is driving me to madness!  It is known smoking increases ACE2 enzyme deployment:

 

https://www.medrxiv....3.18.20038455v1

 

"Current smoking also significantly increased ACE2 expression levels compared with never smokers"

 

The virus enters through the ACE2 RECEPTOR sites of lung cells, so more of these (ACE2 receptor sites) are bad, but the ACE2 enzyme itself is actually protective against inflammation and perhaps the "ground glass opacities" seen on CT that develop almost universally during the very early stages of COVID disease?  

 

We've simply got to get to the bottom of this.  What "mimic" might there be for smoking that might duplicate this "far stronger effect than any drug trialed to date"?  

 

Please help me!  

Remember the discovery from Dutch scientists about bradykinin inciting most if not all of the damage, including the subsequent cytokine storm?

 

I posted about it a few pages back. They basically claimed the following: block or decrease the effect of bradykinin and no harm will be done to the organs. 

 

So covid-19 enters the human body and then using the ace2 receptor to enter a cell --> it then hijacks a host cell and starts doing its thing--> ace2 receptor vanishes from the cells where covid-19 enters -->  bradykinin gets free reign (ace2 keeps bradykinin in check: no ace2 = NO protector around) --> vascular leakage ---> upregulation proinflammatory cytokines ---> cytokin storm --> organ failure (especially the lungs).

 

Well, i found this:

 

Acute administration of nicotine in the rat decreases bradykinin-induced plasma extravasation

 

https://www.scienced...30645229290304K

 

This literally means that nicotine decreases the leakage of blood, lymph, or other fluid from a blood vessel caused by bradykinin.

 

So Nicotine replaces the role of ACE2 (acting as a guardian and trying to keep Bradykinin in check) which has been taken out by COVID-19 once it enters the host cell.

 

Any thoughts guys?

Edited by izan82, 16 April 2020 - 02:53 PM.

[lancebr]

I think this says it all (as you pointed out in your followup post): "We recorded 52 patients (AS-7, EU-21, AF-3, NA-14, SA-7) who received Ivermectin (150 mcg/Kg) once after mechanical ventilation was instituted... Compared to 1,918 conventionally treated patients we observed a survival benefit for ivermectin (mortality rate 18.6% vs 7.7%; HR 0.18, 95% CI (0.07-0.48), log rank (Mantel-Cox) p<0.001). The hospital length of stay was 15.7 +/- 8.1 days vs 10.9 +/- 6.1 days, p<0.001 and intensive care unit length of stay 8.2 +/- 6.2 days vs 6.0 +/- 3.9 days, p<0.001 respectively."

 

So they gave them a single substandard dose, then mortality dropped by 58%. They also indicate that the length of hospital and/or ICU treatment dropped impressively, but that would be consistent with a higher survival ratio, so it adds essentially no information and thus doesn't suppress the P value any further. But P of 0.1% is already remarkable. Everything "needs more study", but this deserves more study!

 

I think one important point is that they gave the one dose to patients after mechanical ventilation was instituted. 

 

So if those patients were that bad off that they had to have mechanical ventilation, then just think about what this

could do for patients that haven't progressed that far.
 

[lancebr]

Remember the discovery from Dutch scientists about bradykinin inciting most if not all of the damage, including the subsequent cytokine storm?

 

I posted about it a few pages back. They basically claimed the following: block or decrease the effect of bradykinin and no harm will be done to the organs. 

 

So covid-19 enters the human body and then using the ace2 receptor to enter a cell --> it then hijacks a host cell and starts doing its thing--> ace2 receptor vanishes from the cells where covid-19 enters -->  bradykinin increases (ace2 keeps bradykinin in check: no ace2 = NO protector around) --> vascular leakage ---> upregulation proinflammatory cytokines ---> cytokin storm --> organ failure (especially the lungs).

 

Well, i found this:

 

Acute administration of nicotine in the rat decreases bradykinin-induced plasma extravasation

 

https://www.scienced...30645229290304K

 

This literally means that nicotine decreases the leakage of blood, lymph, or other fluid from a blood vessel caused by bradykinin.

 

So Nicotine replaces the role of ACE2 (acting as a guardian and trying to keep Bradykinin in check) which has been taken out by COVID-19 once it enters the host cell.

 

Any thoughts guys?

 

As noted earlier in the thread melatonin and melatonin-mimicking drugs inhibit bradykinin.

 

So might be wise to have some melatonin on hand just in case.

 

In addition to melatonin there is the following:

 

"Many medicinal plants (e.g., C. ambrosioides, Mandevilla velutina, and Helminthostachys zeylanica) inhibit the effects

of bradykinin. Amentoflavone from Ginkgo Biloba, cupressuflavone from Cupressus tarulosa, vitexin from Ochrocarpus

longifolius and Arnebia hispidissima, jotrophone from Jatropha elliptica, and plants rich in vitamin K have been found to

be potent antagonists of bradykinin"

 

https://www.scienced...ence/bradykinin

 

Another one is also Aloe Vera:

 

https://www.ncbi.nlm...les/PMC3611630/

 

Also Bromelain

 

 

 

Edited by lancebr, 16 April 2020 - 03:18 PM.

[Hip]

I think one important point is that they gave the one dose to patients after mechanical ventilation was instituted. 

 

So if those patients were that bad off that they had to have mechanical ventilation, then just think about what this

could do for patients that haven't progressed that far.
 

 

Any benefit of ivermectin on COVID-19 will not come from its antiviral effect, from what I can make out.

 

By my pharmacokinetic calculation, you would need an ivermectin oral dose of 28.6 grams just to achieve the 5 μM concentration used in an in vitro antiviral study. That's too high to make ivermectin a viable antiviral, as it could be a lethal dose. The lethal ivermectin dose in rats is around 50 mg/kg. Ref: 1

 

 

 

However, ivermectin is also an immunostimulant, so perhaps that immune boost might explain any benefits:

 

Effect of ivermectin on the immune response in mice

[zorba990]

Remember the discovery from Dutch scientists about bradykinin inciting most if not all of the damage, including the subsequent cytokine storm?

I posted about it a few pages back. They basically claimed the following: block or decrease the effect of bradykinin and no harm will be done to the organs.

So covid-19 enters the human body and then using the ace2 receptor to enter a cell --> it then hijacks a host cell and starts doing its thing--> ace2 receptor vanishes from the cells where covid-19 enters --> bradykinin gets free reign (ace2 keeps bradykinin in check: no ace2 = NO protector around) --> vascular leakage ---> upregulation proinflammatory cytokines ---> cytokin storm --> organ failure (especially the lungs).

Well, i found this:

Acute administration of nicotine in the rat decreases bradykinin-induced plasma extravasation

https://www.scienced...30645229290304K

This literally means that nicotine decreases the leakage of blood, lymph, or other fluid from a blood vessel caused by bradykinin.

So Nicotine replaces the role of ACE2 (acting as a guardian and trying to keep Bradykinin in check) which has been taken out by COVID-19 once it enters the host cell.

Any thoughts guys?

It's been discussed before, but why not use Hesperidin to block it from attaching to the ACE2 receptor?
https://www.google.c...RxAQa1hdrojs5jW


Revealing the Potency of Citrus and Galangal Constituents to Halt SARS-CoV-2 Infection

Citrus sp. could be addressed as the best herb to be promoted to combat beta coronavirus, included SARS-CoV-2, in the forms of therapeutical or prophylaxis agents. Despite hesperidin, Citrus sp. contains several methoxy flavonoids, such as hesperetin, tangeretin, naringenin, and nobiletin which perform low binding energy (comparable with the reference ligands, lopinavir and nafamostat) to the three essential receptors. These low binding energies allowing those compounds to interact tightly to the target proteins. These interactions will contribute to the inhibitory effect against virus infection and replication. Those methoxy flavonoids exist in the whole fruit and more abundant in the peel in most of Citrus sp. types (Nogata et al., 2006) allowing us to easily access to the sources of compounds. In addition, those main compounds of Citrus sp. exhibit antiviral activities on several types of viruses with
Page 5 of 8
Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 12 March 2020 doi:10.20944/preprints202003.0214.v1
several mechanisms (Table 2). These findings seem to be in line with and support for the findings of its mechanism of action as an antiviral. Since, citrus fruit is a nontoxic material, it could be prepared as a food or mixed with other herbal medicines as “jamu”. Taken together, Citrus sp. and galangal can be used as agents to overcome the impact of the coronavirus in a form that is easily consumed so that people can do it without special assistance.

[Florin]

Three studies show no benefit from CQ/HCQ in treating COVID-19. One study also used ceftriaxone and azithromycin. But the HCQ hype train says: no zinc, no cure!

 

Chloroquine diphosphate in two different dosages as adjunctive therapy of hospitalized patients with severe respiratory syndrome in the context of coronavirus (SARS-CoV-2) infection: Preliminary safety results of a randomized, double-blinded, phase IIb clinical trial (CloroCovid-19 Study)

https://www.medrxiv....4.07.20056424v2
 

Hydroxychloroquine in patients with COVID-19: an open-label, randomized, controlled trial

https://www.medrxiv....4.10.20060558v1
 

No evidence of clinical efficacy of hydroxychloroquine in patients hospitalized for COVID-19 infection with oxygen requirement: results of a study using routinely collected data to emulate a target trial

https://www.medrxiv....4.10.20060699v1

Edited by Florin, 16 April 2020 - 08:39 PM.

[lancebr]

It's been discussed before, but why not use Hesperidin to block it from attaching to the ACE2 receptor?
https://www.google.c...RxAQa1hdrojs5jW


Revealing the Potency of Citrus and Galangal Constituents to Halt SARS-CoV-2 Infection

Citrus sp. could be addressed as the best herb to be promoted to combat beta coronavirus, included SARS-CoV-2, in the forms of therapeutical or prophylaxis agents. Despite hesperidin, Citrus sp. contains several methoxy flavonoids, such as hesperetin, tangeretin, naringenin, and nobiletin which perform low binding energy (comparable with the reference ligands, lopinavir and nafamostat) to the three essential receptors. These low binding energies allowing those compounds to interact tightly to the target proteins. These interactions will contribute to the inhibitory effect against virus infection and replication. Those methoxy flavonoids exist in the whole fruit and more abundant in the peel in most of Citrus sp. types (Nogata et al., 2006) allowing us to easily access to the sources of compounds. In addition, those main compounds of Citrus sp. exhibit antiviral activities on several types of viruses with
Page 5 of 8
Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 12 March 2020 doi:10.20944/preprints202003.0214.v1
several mechanisms (Table 2). These findings seem to be in line with and support for the findings of its mechanism of action as an antiviral. Since, citrus fruit is a nontoxic material, it could be prepared as a food or mixed with other herbal medicines as “jamu”. Taken together, Citrus sp. and galangal can be used as agents to overcome the impact of the coronavirus in a form that is easily consumed so that people can do it without special assistance.

 

There was some contradictory information that hesperidin would probably not bind to target the correct interface that would stop the virus:

 

"Based on the virtual screening results of ACE2 protein, anti-diabetes drug troglitazone, anti-hypertensive drug losartan, analgesia drug
ergotamine, anti-bacterial drug cefmenoxime, and hepatoprotective drug silybin, etc., were predicted to bind with ACE2 with low energy.
The natural products, such as phyllaemblicin G7 from Phyllanthus emblica, xanthones from the plants of Swertiagenus, neohesperidin
and hesperidin from Citrus aurantium, exhibited potentially high binding affinity to ACE2 protein. However, none of above ACE2
binding compounds was predicted to target the ACE2–RBD interface."

 

https://www.scienced...211383520302999

 

So based upon that information they do not predict that those binding compounds will target the ACE2-RBD interface.  So if that is true then
those compounds will bind to the ACE2 receptor, but just not where it is needed to target the ACE2-RBD interface to stop this virus.

 

The only information that I have seen about a substance that might specifically target the ACE2-RBD interface was from Withania somnifera:

 

https://www.research...cle/rs-17806/v1

 

The issue with any of these docking models is that even if some substances like hesperidin or withania dock to the ACE2 it doesn't

guarantee that it will stop the virus from docking if the virus has a stronger affinity for docking to ACE2 compared to that of the

other substances.

 

It is not going to hurt to take either hesperidin or the herb withania (ashwanghda) but I would not stake my life on them working

since it is just based upon docking models.  Out of the two if I was going to spend the money along with the other many supplements

I have bought because of this virus then I would go with withania since it seem to specifically target the ACE2-RBD interface.

 

 

Edited by lancebr, 16 April 2020 - 08:56 PM.

[lancebr]

Any benefit of ivermectin on COVID-19 will not come from its antiviral effect, from what I can make out.

 

By my pharmacokinetic calculation, you would need an ivermectin oral dose of 28.6 grams just to achieve the 5 μM concentration used in an in vitro antiviral study. That's too high to make ivermectin a viable antiviral, as it could be a lethal dose. The lethal ivermectin dose in rats is around 50 mg/kg. Ref: 1

 

 

 

However, ivermectin is also an immunostimulant, so perhaps that immune boost might explain any benefits:

 

Effect of ivermectin on the immune response in mice

 

I agree based upon that study to kill the virus you would need an extremely high amount, but it seems like researchers

think that it will work by slowing down the replication giving the body enough time to fight the virus off:

 

"The coronavirus is not a parasite, but researchers suggest ivermectin treats it like one in a sense, blocking viral RNA from

invading health cells. The RNA is then slowed from replicating, giving the patient’s immune system time to fight the illness off.

Researchers said the next step is to “determine the correct human dosage — ensuring the doses shown to effectively treat

the virus in vitro are safe for humans.”
 

So maybe the lower doses just slow it down, instead of killing it like the extreme higher doses do, giving the body enough time

to fight it off.

[Mind]

Three studies show no benefit from CQ/HCQ in treating COVID-19. One study also used ceftriaxone and azithromycin. But the HCQ hype train says: no zinc, no cure!

 

Chloroquine diphosphate in two different dosages as adjunctive therapy of hospitalized patients with severe respiratory syndrome in the context of coronavirus (SARS-CoV-2) infection: Preliminary safety results of a randomized, double-blinded, phase IIb clinical trial (CloroCovid-19 Study)

https://www.medrxiv....4.07.20056424v2
 

Hydroxychloroquine in patients with COVID-19: an open-label, randomized, controlled trial

https://www.medrxiv....4.10.20060558v1
 

No evidence of clinical efficacy of hydroxychloroquine in patients hospitalized for COVID-19 infection with oxygen requirement: results of a study using routinely collected data to emulate a target trial

https://www.medrxiv....4.10.20060699v1

 

Just quickly going through these.

 

1. Found no benefit with 81 patients and said high dose HCQ caused more problems than low dose (already known). Also used azithromycin.

 

2. Found HCQ alleviated clinical symptoms of the disease but did not provide a statistically significant benefit for the primary clinical endpoint.

 

3. Found a small benefit to the use of HCQ but it was not statistically significant.

 

Am I reading those correct?

[lancebr]

Just quickly going through these.

 

1. Found no benefit with 81 patients and said high dose HCQ caused more problems than low dose (already known). Also used azithromycin.

 

2. Found HCQ alleviated clinical symptoms of the disease but did not provide a statistically significant benefit for the primary clinical endpoint.

 

3. Found a small benefit to the use of HCQ but it was not statistically significant.

 

Am I reading those correct?

 

The first study did not use HCQ...it used the regular Chloroquine which is known to have more side effects.
 

[DanCG]

There was some contradictory information that hesperidin would probably not bind to target the correct interface that would stop the virus:

 

"Based on the virtual screening results of ACE2 protein, anti-diabetes drug troglitazone, anti-hypertensive drug losartan, analgesia drug
ergotamine, anti-bacterial drug cefmenoxime, and hepatoprotective drug silybin, etc., were predicted to bind with ACE2 with low energy.
The natural products, such as phyllaemblicin G7 from Phyllanthus emblica, xanthones from the plants of Swertiagenus, neohesperidin
and hesperidin from Citrus aurantium, exhibited potentially high binding affinity to ACE2 protein. However, none of above ACE2
binding compounds was predicted to target the ACE2–RBD interface."

 

https://www.scienced...211383520302999

 

So based upon that information they do not predict that those binding compounds will target the ACE2-RBD interface.  So if that is true then
those compounds will bind to the ACE2 receptor, but just not where it is needed to target the ACE2-RBD interface to stop this virus.

 

...

It is not going to hurt to take either hesperidin or the herb withania (ashwanghda) but I would not stake my life on them working

since it is just based upon docking models.  Out of the two if I was going to spend the money along with the other many supplements

I have bought because of this virus then I would go with withania since it seem to specifically target the ACE2-RBD interface.

 

Your point about hesperidin was raised earlier in the thread. The cited paper shows multiple potential bindings for hesperidin. Besides binding to ACE2, hesperidin binds to Spike protein: "By superimposing the ACE2–RBD complex to the hesperidin–RBD complex, a distinct overlap of hesperidin with the interface of ACE2 could be observed , suggesting hesperidin may disrupt the interaction of ACE2 with RBD."  So hesperidin still looks like something worth trying. (this is the short version of comment #517)

Of course, these in silico screens don't always accurately predict binding in real life. This really needs to be put to the test. It's been a couple of weeks. What are they doing with their time?

 

Edited by DanCG, 16 April 2020 - 11:58 PM.

[lancebr]

 

There was some contradictory information that hesperidin would probably not bind to target the correct interface that would stop the virus:

 

"Based on the virtual screening results of ACE2 protein, anti-diabetes drug troglitazone, anti-hypertensive drug losartan, analgesia drug
ergotamine, anti-bacterial drug cefmenoxime, and hepatoprotective drug silybin, etc., were predicted to bind with ACE2 with low energy.
The natural products, such as phyllaemblicin G7 from Phyllanthus emblica, xanthones from the plants of Swertiagenus, neohesperidin
and hesperidin from Citrus aurantium, exhibited potentially high binding affinity to ACE2 protein. However, none of above ACE2
binding compounds was predicted to target the ACE2–RBD interface."

 

https://www.scienced...211383520302999

 

So based upon that information they do not predict that those binding compounds will target the ACE2-RBD interface.  So if that is true then
those compounds will bind to the ACE2 receptor, but just not where it is needed to target the ACE2-RBD interface to stop this virus.

 

...

It is not going to hurt to take either hesperidin or the herb withania (ashwanghda) but I would not stake my life on them working

since it is just based upon docking models.  Out of the two if I was going to spend the money along with the other many supplements

I have bought because of this virus then I would go with withania since it seem to specifically target the ACE2-RBD interface.

 

Your point about hesperidin was raised earlier in the thread. The cited paper shows multiple potential bindings for hesperidin. Besides binding to ACE2, hesperidin binds to Spike protein: "By superimposing the ACE2–RBD complex to the hesperidin–RBD complex, a distinct overlap of hesperidin with the interface of ACE2 could be observed , suggesting hesperidin may disrupt the interaction of ACE2 with RBD."  So hesperidin still looks like something worth trying. (this is the short version of comment #517)

Of course, these in silico screens don't always accurately predict binding in real life. This really needs to be put to the test. It's been a couple of weeks. what are they doing with their time?

 

 

It's not my point....it is the point made by the researchers in the paper who believed that hesperidin would not target

the area of the receptor where it is needed to interrupt the virus.

"The natural products, such as phyllaemblicin G7 from Phyllanthus emblica, xanthones from the plants of Swertiagenus,

neohesperidin and hesperidin from Citrus aurantium, exhibited potentially high binding affinity to ACE2 protein.

However, none of above ACE2 binding compounds was predicted to target the ACE2–RBD interface."

 

Another very important point made by the researchers in that paper was the following:

 

"TMPRSS2 was known to cut the Spike to trigger the infection of SARS-CoV and MERS-CoV. Studies have shown that

inhibiting the enzyme activity of TMPRSS2 can prevent some coronaviruses from entering host cells As a possible target

for anti-viral drug discovery, the virtual screen results (shown in Supporting excel files) predicted many anti-bacterial

drugs (pivampicillin, hetacillin, cefoperazone and clindamycin) and anti-virus natural compounds (phyllaemblicin G7,

neoandrographolide, kouitchenside I), etc. to be potential TMPRSS2 inhibitors."

 

The natural compounds they listed to inhibit TMPRSS2 sounds much more important in stopping a virus that is triggered

by TMPRSS2. By inhibiting TMPRSS2 you would not have to worry about if the compound is binding at the right point

in the receptor or if the compound has a stronger binding affinity than the virus does.

 

It appears the Covid 19 virus does require TMPRSS2 to enter the cells and inhibiting that can be a treatment against the virus:

 

https://www.contagio...prevent-covid19

 

https://www.cell.com...8674(20)30229-4

 

 

 

 

Edited by lancebr, 17 April 2020 - 12:29 AM.

[DanCG]

It's not my point....it is the point made by the researchers in the paper who believed that hesperidin would not target

the area of the receptor where it is needed to interrupt the virus.

"The natural products, such as phyllaemblicin G7 from Phyllanthus emblica, xanthones from the plants of Swertiagenus,

neohesperidin and hesperidin from Citrus aurantium, exhibited potentially high binding affinity to ACE2 protein.

However, none of above ACE2 binding compounds was predicted to target the ACE2–RBD interface."

 

 

 

By, "your point" I was was simply referring to your reference to a quote from the paper. I did not mean to imply that I thought you were imposing your own interpretation. 

 

My intent was to point out that the authors of the paper wrote that " hesperidin may disrupt the interaction of ACE2 with RBD." because hesperidin binds to Spike, not just ACE2.:

"The only compound that could target the binding interface between Spike and ACE2 was hesperidin, as shown in Fig 6A. Hesperidin was predicted to lie on the middle shallow pit of the surface of RBD of Spike...By superimposing the ACE2–RBD complex to the hesperidin–RBD complex, a distinct overlap of hesperidin with the interface of ACE2 could be observed ( Fig. 6C), suggesting hesperidin may disrupt the interaction of ACE2 with RBD."

"

[resveratrol_guy]

Three studies show no benefit from CQ/HCQ in treating COVID-19. One study also used ceftriaxone and azithromycin. But the HCQ hype train says: no zinc, no cure!

 

Chloroquine diphosphate in two different dosages as adjunctive therapy of hospitalized patients with severe respiratory syndrome in the context of coronavirus (SARS-CoV-2) infection: Preliminary safety results of a randomized, double-blinded, phase IIb clinical trial (CloroCovid-19 Study)

https://www.medrxiv....4.07.20056424v2
 

Hydroxychloroquine in patients with COVID-19: an open-label, randomized, controlled trial

https://www.medrxiv....4.10.20060558v1
 

No evidence of clinical efficacy of hydroxychloroquine in patients hospitalized for COVID-19 infection with oxygen requirement: results of a study using routinely collected data to emulate a target trial

https://www.medrxiv....4.10.20060699v1

 

Good post. Just kinda depressing because these seem to have been foregone conclusions even back when they started. Maybe we should have another study to see if HCQ combined with ice cream is more effective.

 

"But the HCQ hype train says: no zinc, no cure!" -- Hopefully that will inspire some group to refute all the fools -- like me -- who think it matters. I would love to see better science, while not impeding informed access.

Edited by resveratrol_guy, 17 April 2020 - 02:49 AM.

[resveratrol_guy]

Acute administration of nicotine in the rat decreases bradykinin-induced plasma extravasation

 

Any thoughts guys?

 

Yes. First, this sounds like a compelling theoretical approach. Maybe, despite their elevated blood pressure, we should consider giving nicotine patches, at various doses, to serious patients, in addition to other measures known to blunt cytokine storms.

 

Secondly, it seems like this can't actually explain the smoker anomaly because they sure aren't smoking in the ICU. Unless their arteries have been so stiffened by years of the habit, that they actually survive the bradykinin rampage. Hmm...

[Florin]

Good post. Just kinda depressing because these seem to have been foregone conclusions even back when they started. Maybe we should have another study to see if HCQ combined with ice cream is more effective.

 

"But the HCQ hype train says: no zinc, no cure!" -- Hopefully that will inspire some group to refute all the fools -- like me -- who think it matters. I would love to see better science, while not impeding informed access.

 

Well, there were reports that HCQ by itself is useless, so this isn't exactly a real surprise.

 

Fortunately, there are ongoing clinical trials testing H+Z for COVID-19.

 

https://clinicaltria...hloroquine zinc

Edited by Florin, 17 April 2020 - 04:32 AM.

[lancebr]

This papers believes that people who had the quadrivalent vaccine have a better outcome from

Covid 19 compared to people who received the Trivalent:

 

"Comparing the influenza vaccine used by different national health systems in Europe suggests

that patients with COVID-19 may have better outcomes if the influenza vaccine is Quadrivalent

and includes the B/Massachusetts/2/2012 (Yamagata lineage)."

 

https://www.research...OVID-19-v04.pdf

[pamojja]

This really needs to be put to the test. It's been a couple of weeks. what are they doing with their time?

 

Take a close look at this weird thread: https://vitamincfoun...php?f=3&t=14790

 

It appears one of its authors is participating, who's been in China and for a short time in Italy to help out and test his protocol. If that is true, he seems to be waiting for the highest bidder on his patent. Something like 20 millions. Somewhere in the thread he said he used IV-grade hesperidinmethychalcone, which he alledgely bought up in bulk, and therefore isn't easy to find now.
 

[Kalliste]

This is a long thread and nobody has touched upon caffeine yet, wonder how that will turn out? I drink a lot of coffee. 

 

 

Yes. First, this sounds like a compelling theoretical approach. Maybe, despite their elevated blood pressure, we should consider giving nicotine patches, at various doses, to serious patients, in addition to other measures known to blunt cytokine storms.

 

Secondly, it seems like this can't actually explain the smoker anomaly because they sure aren't smoking in the ICU. Unless their arteries have been so stiffened by years of the habit, that they actually survive the bradykinin rampage. Hmm...

 

I bought nicotine gums. First sign of symtoms it will be Vit C, Nicotine gums and melatonine. Those things seem pretty innocent too, not likely to make things worse. Actually smoking is probably going to be a bad thing.

 

 

[Kalliste]

 

 

Glucosamine administration may up-regulate MAVS activation

Another key mediator of type 1 interferon response is the mitochondrial antiviral-signaling protein (MAVS), which oligomerizes in response to activation of cytosolic RNA virus detectors RIG-1 and MDA5, and subsequently participates in the activation of the transcription factor interferon regulatory factor 3 (IRF3).²⁵ (TLR7 signaling likewise contributes to activation of this factor; both pathways promote the K63-linked polyubiquitination and activation of the tank-binding kinase-1 – TBK1 – which in turn activates IRF3 via phosphorylation.^{26., 27., 28.}) Duan and colleagues have recently shown that RNA virus infection promotes O-GlcNacylation of MAVS on multiple sites, and that this renders MAVS susceptible to the K63-linked ubiquitination that enables it to activate IRF3.²⁹ Moreover, they show that, the more extensive this O-GlcNacylation is, the more effectively MAVS is activated. Hence, they are able to demonstrate that measures which suppress or amplify the cellular pool of UDP-N-acetylglucosamine – the substrate for O-GlcNacylation – correspondingly suppress or amplify the activation of MAVS. They then proceed to demonstrate that feeding mice a glucosamine-enriched diet (2.5% by weight) markedly enhances the survival of wild-type mice infected with influenza virus, whereas this provided no protection in mice in which MAVS, type 1 interferons, or O-GlcNac transferase (the mediator of O-GlcNacylation) were genetically absent.

This striking new finding points to the possibility that high-dose glucosamine supplementation might aid prevention and control of RNA virus infections. Whereas the hexosamine biosynthesis pathway is capable of generating UDP-N-acetylglucosamine in the absence of exogenous glucosamine, glucosamine administration can further enhance the intracellular pool of this compound, thereby boosting the extent of O-GlcNacylation evoked by viral infection.³⁰ The dietary dose employed in this study is quite high in the context of previous clinical experience – 2.5% of a human diet providing 400 g dry weight daily would correspond to 10 g glucosamine – but an intake of 3 g daily would be practical and is within the range of previous clinical experience.³¹ Rather high intakes may be required for significant clinical benefit, inasmuch as this compound is rather inefficiently absorbed after oral administration.³²

https://www.ncbi.nlm...les/PMC7130854/

 

Glucosamine and some other nutraceuticals considered such as inducers of ferulic acid. 

[resveratrol_guy]

I've had this nagging urge to see if I can tease anything out of the exit survival ratios ((resolved - dead) / resolved) of various jurisdictions. It's really tough to compare countries in a meaningful way, but it might be informative to compare US states and protectorates.

 

So what did I learn? Not much. Perhaps you can see something that I've overlooked. I did notice that the first few nonzero ESR states tend to be heavier in urban black population fractions, and the ones with the best scores are either arid and sparsely populated or humid and tropical. The US Virgin Islands is predominantly black, but scores very well; it's also a great source of UV, seafood, and steep terrain.

 

Lousiana is a hotbed of obesity, whereas the US Virgin Islands are just the opposite; I've been to both places since 2015, and it's obvious to me that the blacks follow the overall trend in this regard. (Recall that obesity is the top survival determinant in COVID19.) So despite the skew in the data, I don't see any good reason to conclude that being black is a causal source of risk.

 

The data is from Worldometers as of an hour or so before this post. You can copy and paste it into a CSV in a text editor if you wish to manipulate it with a spreadsheet app. The last column is ESR times 1000, so for instance 901 means 90.1%. It's sorted from worst to best survival. I recommend ignoring the first few entries with 0% ESR, which could simply indicate the lack of any requirement to count survivors.

 

 

State,CaseCount,ActiveCases,ResolvedCases,Deaths,ESR

Mississippi,3624,3495,129,129,0
NorthernMarianaIslands,13,11,2,2,0
Oregon,1736,1672,64,64,0
SouthCarolina,3931,3822,109,109,0
Vermont,768,733,35,35,0
Indiana,9542,9051,491,477,28
Louisiana,22532,21326,1206,1156,41
Illinois,25733,24611,1122,1072,44
Georgia,16368,15720,648,617,47
Connecticut,15884,14848,1036,971,62
PuertoRico,1043,983,60,56,66
RhodeIsland,3838,3723,115,105,86
Alabama,4404,4247,157,137,127
Michigan,29263,26727,2536,2093,174
Ohio,8414,7905,509,389,235
NewJersey,75317,70528,4789,3518,265
Wisconsin,3875,3591,284,197,306
Arizona,4234,4014,220,150,318
Idaho,1609,1544,65,41,369
Pennsylvania,27735,26248,1487,837,437
Nebraska,1066,1020,46,24,478
Florida,23340,22028,1312,668,490
Missouri,5178,4826,352,168,522
Colorado,8675,7803,872,374,571
California,28156,25833,2323,973,581
NewYork,226198,186205,39993,16106,597
Maryland,10784,9656,1128,392,652
Kentucky,2429,1994,435,129,703
Washington,11152,8854,2298,583,746
Kansas,1603,1283,320,80,750
Virginia,6889,5730,1159,208,820
NorthCarolina,5608,4577,1031,148,856
Massachusetts,32181,22818,9363,1245,867
NewMexico,1597,1258,339,44,870
WashingtonDC,2350,1717,633,81,872
Delaware,2075,1645,430,52,879
Nevada,3321,2010,1311,142,891
Oklahoma,2357,1071,1286,131,898
Texas,16638,12557,4081,404,901
Utah,2683,2444,239,21,912
Minnesota,1912,798,1114,94,915
WestVirginia,739,579,160,13,918
Alaska,300,181,119,9,924
Maine,796,436,360,27,925
NewHampshire,1211,722,489,34,930
Guam,135,57,78,5,935
Arkansas,1620,1035,585,37,936
Tennessee,6262,3925,2337,141,939
Iowa,2141,1094,1047,60,942
NorthDakota,393,221,172,9,947
Montana,415,190,225,7,968
Hawaii,541,158,383,9,976
UnitedStatesVirginIslands,51,4,47,1,978
SouthDakota,1311,931,380,7,981
Wyoming,401,223,178,2,988
 

Edited by resveratrol_guy, 17 April 2020 - 12:48 PM.

[resveratrol_guy]

Well, there were reports that HCQ by itself is useless, so this isn't exactly a real surprise.

 

Fortunately, there are ongoing clinical trials testing H+Z for COVID-19.

 

https://clinicaltria...hloroquine zinc

 

Yeah that was exactly my point. At least you found that there are other studies (currently 3) looking into the zinc combo, as either a prophylactic or a therapy. You made my day! Not that the results will help us anytime soon, but at least it means that it's probably being taken seriously enough to not get tossed out with the monotherapy bathwater.
 

[resveratrol_guy]

This papers believes that people who had the quadrivalent vaccine have a better outcome from

Covid 19 compared to people who received the Trivalent:

 

"Comparing the influenza vaccine used by different national health systems in Europe suggests

that patients with COVID-19 may have better outcomes if the influenza vaccine is Quadrivalent

and includes the B/Massachusetts/2/2012 (Yamagata lineage)."

 

https://www.research...OVID-19-v04.pdf

 

Well that's interesting. Rather than to posit any antigen relationship to COVID19 (why?), it seems more probable that the inclusion of the B/Yamagata 2012 strain is just a proxy for having been vaccinated more recently, thereby keeping the immune system on guard. Or perhaps a proxy for more forward-thinking health systems which are more aggressively hugging the leading edge science and therefore more likely to be on top of COVID19 mitigation efforts. Hmm...

 

(Unfortunately I can't view the paper.)
 

[resveratrol_guy]

I bought nicotine gums. First sign of symtoms it will be Vit C, Nicotine gums and melatonine. Those things seem pretty innocent too, not likely to make things worse. Actually smoking is probably going to be a bad thing.

 

I would say hold off on the nicotine gum until you detect shortness of breath, then chew it on the way to the hospital if it comes to that (because they'll likely try to take it away from you, or you'll otherwise lose access to it). I suppose a patch would also help you to keep dosing surreptitiously after being admitted, at least for a while. The last thing we want to do is raise your blood pressure when your heart is pounding in an effort to create a fever, while there is no bradykinin overload to correct.

[DanCG]

Take a close look at this weird thread: https://vitamincfoun...php?f=3&t=14790

 

It appears one of its authors is participating, who's been in China and for a short time in Italy to help out and test his protocol. If that is true, he seems to be waiting for the highest bidder on his patent. Something like 20 millions. Somewhere in the thread he said he used IV-grade hesperidinmethychalcone, which he alledgely bought up in bulk, and therefore isn't easy to find now.
 

 

Interesting thread. I can’t quite figure it out. Apparently the person who goes by the handle eDOC is an author on the structure search paper that identified hesperidin as a possible inhibitor.

 

He says, “Hesperidin Methyl Chalcone (HMC) 99% IV grade infusions along with some others provide almost a near +99% prophylaxis in unaffected, and do play a role once the infection is diagnosed. It showed in the trials conducted and patients I treated. The others at this moment cannot reveal since the deal is going through, once it's over hopefully soon shall reveal.
Am glad that I stocked the IV grade back in Jan, now it's a bit hard to get.”

 

He mentions a deal in the works, but it looks like no patent has been filed. Post #34. Some of his later comments make it seem that he would be willing to sell the rights to big pharma even if he knows that will suppress it in favor of vaccines.

 

Anyway, natural hesperidin would not be patentable as a product in the US. He might be able to get a method of treatment patent or maybe he could come up with a non-obvious formulation.

[Daniel Cooper]

Anyone know the half life of Hesperidin and what would be a good dose? What's the oral availability like?

 

 

 

 

 

 

 

 

Edited by Daniel Cooper, 17 April 2020 - 01:55 PM.

[resveratrol_guy]

"Coronavirus: The Dead Speak!"

 

Pathologist Chris Martenson discusses portmortem findings on 4 COVID19 victims. Multiple organ failure, chiefly the lungs. Be warned: not for the faint of heart!

 

https://www.youtube....h?v=PZI0JJXIRUw

[Daniel Cooper]

Answering my own question.
 
Hesperidin half life = 6hrs
 
In Vivo pharmacokinetics of hesperidin are affected by treatment with glucosidase-like BglA protein isolated from yeasts

[Daniel Cooper]

Absorption and Metabolic Behavior of Hesperidin (Rutinosylated Hesperetin) after Single Oral Administration to Sprague-Dawley Rats