3083 replies to this topic

[Izan]

Isn't that why the Japanese made apolactoferrin? Lactoferring without the bound iron? To also increase its absorption rate?

 

The most studied mechanism of antiviral activity of lactoferrin is its diversion of virus particles from the target cells. Many viruses tend to bind to the lipoproteins of the cell membranes and then penetrate into the cell.^[50] Lactoferrin binds to the same lipoproteins thereby repelling the virus particles. Iron-free apolactoferrin is more efficient in this function than hololactoferrin. (hololactoferrin is the 'regular' lactoferrin)

 

 

 

https://www.scienced...001954?via=ihub

 

 

[Izan]

COVID-19 MUTATIONS, VACCINES & NITRIC OXIDE – THE VITAMIN C CONNECTION

 

 

evolutamente.it/covid-19-mutations-vaccines-nitric-oxide-the-vitamin-c-connection/

[Izan]

Very recent study.

 

SARS-CoV-2 invades host cells via a novel route: CD147-spike protein

 

 

Currently, COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been widely spread around the world; nevertheless, so far there exist no specific antiviral drugs for treatment of the disease, which poses great challenge to control and contain the virus. Here, we reported a research finding that SARS-CoV-2 invaded host cells via a novel route of CD147-spike protein (SP). SP bound to CD147, a receptor on the host cells, thereby mediating the viral invasion. Our further research confirmed this finding. First, in vitro antiviral tests indicated Meplazumab, an anti-CD147 humanized antibody, significantly inhibited the viruses from invading host cells, with an EC50 of 24.86 μg/mL and IC50 of 15.16 μg/mL. Second, we validated the interaction between CD147 and SP, with an affinity constant of 1.85E-07M. Co-Immunoprecipitation and ELISA also confirmed the binding of the two proteins. Finally, the localization of CD147 and SP was observed in SARS-CoV-2 infected Vero E6 cells by immuno-electron microscope. Therefore, the discovery of the new route CD147-SP for SARS-CoV-2 invading host cells provides a critical target for development of specific antiviral drugs.

 

 

https://www.biorxiv.....03.14.988345v1

[Daniel Cooper]

Luteolin and Quercetin appear to interfere with the virus entering the cell:
 
Small Molecules Blocking the Entry of Severe Acute Respiratory Syndrome Coronavirus into Host Cells

 

 

 

 

[Daniel Cooper]

Anyone have an idea of how much luteolin one would have to consume to achieve a plasma level of 10.6 μM?

 

How much quercetin to get to 83μM?

 

BTW I think I read somewhere that a good strategy would be to consume luteolin with quercetin with the quercetin being a sacrificial decoy to get metabolized first so that you can get some decent plasma levels of luteolin for a period of time.

 

 

 

 

Edited by Daniel Cooper, 16 March 2020 - 02:11 PM.

[Oakman]

Luteolin and Quercetin appear to interfere with the virus entering the cell:
 
Small Molecules Blocking the Entry of Severe Acute Respiratory Syndrome Coronavirus into Host Cells

 

Wondering why you don't mention Galla Chinensis? The two substances in your reference that were most effective at keeping COV-19 from entering cells were Luteolin and TGG (from Galla Chinensis). Galla Chinensis is really cheap @$26/kg and available on Amazon.

 

"TGG and luteolin offer excellent opportunities for further optimization and potential clinical use as anti-SARS drugs. TGG is a component of Galla chinensis that has been used in traditional Chinese medicine for treating chronic coughing."

[lancebr]

Wondering why you don't mention Galla Chinensis? The two substances in your reference that were most effective at keeping COV-19 from entering cells were Luteolin and TGG (from Galla Chinensis). Galla Chinensis is really cheap @$26/kg and available on Amazon.

 

"TGG and luteolin offer excellent opportunities for further optimization and potential clinical use as anti-SARS drugs. TGG is a component of Galla chinensis that has been used in traditional Chinese medicine for treating chronic coughing."

 

So at what dosages would have to be taken to get the results they had in the study?
 

[aim1]

https://m.thechronic...tralia/3973564/

A team of Australian researchers say they've found a cure for the novel coronavirus and hope to have patients enrolled in a nationwide trial by the end of the month.

University of Queensland Centre for Clinical Research director Professor David Paterson told news.com.au today they have seen two drugs used to treat other conditions can wipe out the virus in test tubes.

He said one of the medications, given to some of the first people to test positive for COVID-19 in Australia, had already resulted in "disappearance of the virus" and complete recovery from the infection.

[lancebr]

https://m.thechronic...tralia/3973564/

A team of Australian researchers say they've found a cure for the novel coronavirus and hope to have patients enrolled in a nationwide trial by the end of the month.

University of Queensland Centre for Clinical Research director Professor David Paterson told news.com.au today they have seen two drugs used to treat other conditions can wipe out the virus in test tubes.

He said one of the medications, given to some of the first people to test positive for COVID-19 in Australia, had already resulted in "disappearance of the virus" and complete recovery from the infection.

 

So it is the same drugs that others have been talking about for weeks now....Chloroquine and HIV drug (Ie probably Kaletra)

 

Seems like these drugs are the way to go at the moment if want to be sure to fight this virus.

 

Well luckily I got a prescription for Chloroquine to use as a last resort....don't like the side effects but guess it is better then death.

 

 

Edited by lancebr, 16 March 2020 - 04:34 PM.

[Hip]

Anyone have an idea of how much luteolin one would have to consume to achieve a plasma level of 10.6 μM?

 
You can use data from pharmacokinetic studies on luteolin to calculate the human oral dose required to achieve a plasma concentration of 10.6 μM.
 
A pharmacokinetic study found that a luteolin oral dose of 50 mg/kg given to rats resulted in a peak blood plasma concentration (Cmax) of 5.5 μg/ml. This we can calculate is equal to 19.2 μM. 
 
(To convert to a concentration expressed in μg/ml to μM, we can use the conversion formula: μM = 1000 * μg/ml ÷ molecular weight. The molecular weight of luteolin is 286.24 g/mol, so μM = 1000 * 5.5 ÷ 286.24 = 19.2 μM).
 
 
 
Using the rat-to-human conversion factor of 6.2, a rat dose of 50 mg/kg luteolin converts to human dose of 8 mg/kg. So for an 80 kg human, this is an oral dose of 640 mg. So a human oral dose of 640 mg would lead to a peak blood plasma concentration of 5.5 μg/ml = 19.2 μM.
 
However, that 19.2 μM figure is the total plasma concentration = free luteolin + plasma protein-bound luteolin.

 

But it is only the free luteolin which has an active effect in the body (the free drug principle states that the plasma protein-bound portion of a drug or supplement becomes inactive, and it is only the portion of the substances which floats freely in the blood that is physiologically active in the body). So we need to work out the free luteolin concentration in the blood.
 
To calculate the concentration of free luteolin, we need to look up the plasma protein binding percentage of luteolin. This plasma protein binding figure states what percentage of luteolin binds to proteins in the blood.

 

Unfortunately I cannot find any info on the plasma protein binding of luteolin. But if the plasma protein binding is denoted by P, that is to say, P percent of luteolin binds to plasma proteins, then the blood concentration of free (active) luteolin would be 19.2 * (100 - P) / 100. 
 
So for example, if the plasma protein binding were 90%, then the concentration of free luteolin would be 19.2 * (100 - 90) / 100 = 1.92 μM. But I cannot find the plasma protein binding value for lutein, and plasma protein binding values for drugs and supplements range from 0% to over 99.9%, so it's impossible to guess. The more of your substance binds to proteins, the more that is lost, and has no active effect in the body.
 
 
Thus basically you cannot calculate the precise oral dose until you can find a figure for the plasma protein binding of luteolin.

Edited by Hip, 16 March 2020 - 04:47 PM.

[Daniel Cooper]

Wondering why you don't mention Galla Chinensis? The two substances in your reference that were most effective at keeping COV-19 from entering cells were Luteolin and TGG (from Galla Chinensis). Galla Chinensis is really cheap @$26/kg and available on Amazon.

 

"TGG and luteolin offer excellent opportunities for further optimization and potential clinical use as anti-SARS drugs. TGG is a component of Galla chinensis that has been used in traditional Chinese medicine for treating chronic coughing."

 

Well, I can get pure luteolin readily and so maybe we can work to a dose that achieves a useful plasma level.  I just didn't know if I could find some extract of Galla Chinensis that was standardized to some value of TGG content.  Without that it's difficult to work up a dose.

 

But, let's keep Galla Chinensis/TGG on the table for discussion.  I certainly don't want to excluded it.

[Daniel Cooper]

 
You can use data from pharmacokinetic studies on luteolin to calculate the human oral dose required to achieve a plasma concentration of 10.6 μM.
 
A pharmacokinetic study found that a luteolin oral dose of 50 mg/kg given to rats resulted in a peak blood plasma concentration (Cmax) of 5.5 μg/ml. This we can calculate is equal to 19.2 μM. 
 
(To convert to a concentration expressed in μg/ml to μM, we can use the conversion formula: μM = 1000 * μg/ml ÷ molecular weight. The molecular weight of luteolin is 286.24 g/mol, so μM = 1000 * 5.5 ÷ 286.24 = 19.2 μM).
 
 
 
Using the rat-to-human conversion factor of 6.2, a rat dose of 50 mg/kg luteolin converts to human dose of 8 mg/kg. So for an 80 kg human, this is an oral dose of 640 mg. So a human oral dose of 640 mg would lead to a peak blood plasma concentration of 5.5 μg/ml = 19.2 μM.
 
However, that 19.2 μM figure is the total plasma concentration = free luteolin + plasma protein-bound luteolin.

 

But it is only the free luteolin which has an active effect in the body (the free drug principle states that the plasma protein-bound portion of a drug or supplement becomes inactive, and it is only the portion of the substances which floats freely in the blood that is physiologically active in the body). So we need to work out the free luteolin concentration in the blood.
 
To calculate the concentration of free luteolin, we need to look up the plasma protein binding percentage of luteolin. This plasma protein binding figure states what percentage of luteolin binds to proteins in the blood.

 

Unfortunately I cannot find any info on the plasma protein binding of luteolin. But if the plasma protein binding is denoted by P, that is to say, P percent of luteolin binds to plasma proteins, then the blood concentration of free (active) luteolin would be 19.2 * (100 - P) / 100. 
 
So for example, if the plasma protein binding were 90%, then the concentration of free luteolin would be 19.2 * (100 - 90) / 100 = 1.92 μM. But I cannot find the plasma protein binding value for lutein, and plasma protein binding values for drugs and supplements range from 0% to over 99.9%, so it's impossible to guess. The more of your substance binds to proteins, the more that is lost, and has no active effect in the body.
 
 
Thus basically you cannot calculate the precise oral dose until you can find a figure for the plasma protein binding of luteolin.

 

Great information and I really appreciate your showing your work.

 

What about a plasma protein binding value for quercetin?  It's fairly similar to luteolin chemically and maybe has a similar plasma protein binding value?  In any case, quercetin is interesting in it's own right as it also inhibits corona virus entering the cell, albeit at an apparently higher concentration.

[Daniel Cooper]

So it is the same drugs that others have been talking about for weeks now....Chloroquine and HIV drug (Ie probably Kaletra)

 

Seems like these drugs are the way to go at the moment if want to be sure to fight this virus.

 

Well luckily I got a prescription for Chloroquine to use as a last resort....don't like the side effects but guess it is better then death.

 

 

I couldn't get a script for chloroquine phosphate but I could buy it in powder form - it's sold in aquarium supply stores as a treatment for "ich" in fish.  

 

Needless to say, this is of questionable pedigree so I'll only be using it if things go really sideways.

[Hip]

Great information and I really appreciate your showing your work.

 

What about a plasma protein binding value for quercetin?  It's fairly similar to luteolin chemically and maybe has a similar plasma protein binding value?  In any case, quercetin is interesting in it's own right as it also inhibits corona virus entering the cell, albeit at an apparently higher concentration.

 

 

This study says the "binding of quercetin to normal plasma was extensive", and gives a figure of 99.1%. If luteolin is similar, then about 99% of the substance will be lost, which would be bad news.

 

If the bioavailability is low, and the plasma protein binding is high, you get a double-whammy of losing lots of your substance to poor bioavailability, and then losing even more of the substance to high protein binding.

 

 

 

Many a promising drug in vitro turns out to be useless in vivo because of high protein binding and/or low bioavailability. These are issues that dog drug design. 

[Daniel Cooper]

That is very discouraging indeed.

 

 

[Daniel Cooper]

By that paper I posted earlier, glycyrrhizin (found in licorice root) also inhibits corona virus at a concentration of 607μM.  There can be side effects of this compound when taken in high doses so please inform yourself if you plan to try it.

 

I was unaware till now that it is prescribed in Japan as a drug to lower the risk of Hep C developing into liver cancer.

 

 

[lancebr]

By that paper I posted earlier, glycyrrhizin (found in licorice root) also inhibits corona virus at a concentration of 607μM.  There can be side effects of this compound when taken in high doses so please inform yourself if you plan to try it.

 

I was unaware till now that it is prescribed in Japan as a drug to lower the risk of Hep C developing into liver cancer.

 

So what would the dosage be to get to the 607uM?

[Daniel Cooper]

Information on existing drugs that may have an anti-viral action against coronavirus.  This information is weeks old so presumably the Chinese have a pretty good idea if any of these work.

 

Existing drugs may offer a first-line treatment for coronavirus outbreak

 

 

[Hip]

So what would the dosage be to get to the 607uM?

 

The oral bioavailability of glycyrrhizin is pretty much zero, so you would need to use injections. I believe such glycyrrhizin injections are used in Japan for antiviral purposes.

 

607 μM = 500 μg/ml = 0.5 mg/ml by my calculation. If we assume about 40 liters = 40,000 ml of fluids in the human body, then to get a concentration of 0.5 mg/ml in those fluids, you will need to inject 0.5 * 40,000 = 20,000 mg of glycyrrhizin. That is, 20 grams of glycyrrhizin!

 

But the plasma protein binding for glycyrrhizin is 80%, which means that 80% of what you inject is lost, and the remaining 20% has the active effect. So you would need 5 times amount to compensate for the loss due to protein binding. So you would need to inject 100 grams of glycyrrhizin! Obviously that is a completely non-viable dose.

 

 

 

A lot of the time, studies which examine the antiviral effects of supplements and herbal extracts do so not because the authors think those substances will make useful antivirals for clinical use, but rather because if the substances have antiviral effects in vitro, they can be used as a lead molecule to create a drug based on the molecule, with the drug hopefully having better pharmacokinetic parameters than the original substance. Obviously the pharmacokinetic parameters of glycyrrhizin make it non-viable as an antiviral for coronavirus.

 

Though occasionally you might find a supplement or herb which does have some modest effects against viruses. Often with supplements and herbs it may be their immunomodulatory effects which fight viral infection, rather than any direct antiviral action.

 

 

NOTE: I have brain fog as a result of my chronic fatigue syndrome / myalgic encephalomyelitis, so sometimes I make silly mistakes in my arithmetic. I think the above calc is correct, but you may like to double-check it.

Edited by Hip, 16 March 2020 - 06:50 PM.

[lancebr]

I couldn't get a script for chloroquine phosphate but I could buy it in powder form - it's sold in aquarium supply stores as a treatment for "ich" in fish.  

 

Needless to say, this is of questionable pedigree so I'll only be using it if things go really sideways.

 

I noticed that on some pet/aquarium websites they are sold out of it.  The two aquarium/pet stores in my

area are also sold out. 

 

I just wished it didn't have all the side effects it does...but I guess its just a chance got to take if catch it

and it gets worse.
 

[Dorian Grey]

How NOT to treat coronavirus: 

 

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

 

Louisiana lawyer, 45, is put on ventilator after contracting coronavirus that was initially misdiagnosed as the flu at urgent care center.

 

"On March 8, he went to an urgent care center, where according to his wife, doctors diagnosed him with the flu and prescribed Tamiflu, a steroid and a medicated cough syrup. 

But despite the treatment, which Mark supplemented with Tylenol and Advil to break his nightly fever, his condition deteriorated further".  When he alerted his doctor of the situation, his wife said he was told that it was not uncommon and instructed to keep taking the medications.

At East Jefferson General Hospital a flu test came back negative.  Hospital contacted the urgent care center where Mark had initially sought help and request his paperwork. To her shock and dismay, the woman said she discovered that Mark had tested negative for the flu there too.

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

Looks like we're better off treating ourselves folks.  

[lancebr]

FYI...Dr. Sanjay Gupta on CNN just said that high doses of Vitamin C or Garlic are a sham and

 

should not be expected to help with this virus.

[zorba990]

FYI...Dr. Sanjay Gupta on CNN just said that high doses of Vitamin C or Garlic are a sham and

should not be expected to help with this virus.

I wouldn't say sham, but maybe evidence is not quite there yet due to lack of real interest.
SARS is a corona virus and

https://academic.oup...2/6/1049/731701

Vitamin C and SARS coronavirus
Harri Hemilä
Journal of Antimicrobial Chemotherapy, Volume 52, Issue 6, December 2003, Pages 1049–1050, https://doi.org/10.1093/jac/dkh002
Published: 01 December 2003
pdfPDF Split View Cite
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Share
Keywords: ascorbic acid, pneumonia, severe acute respiratory syndrome
Issue Section: Correspondence
Sir,

Recently, a new coronavirus was identified as the cause of the severe acute respiratory syndrome (SARS).1 In the absence of a specific treatment for SARS, the possibility that vitamin C may show non-specific effects on severe viral respiratory tract infections should be considered. There are numerous reports indicating that vitamin C may affect the immune system,2,3 for example the function of phagocytes, transformation of T lymphocytes and production of interferon. In particular, vitamin C increased the resistance of chick embryo tracheal organ cultures to infection caused by an avian coronavirus.4 Studies in animals found that vitamin C modifies susceptibility to various bacterial and viral infections,3 for example protecting broiler chicks against an avian coronavirus.5 Placebo-controlled trials have shown quite consistently that the duration and severity of common cold episodes are reduced in the vitamin C groups,3 indicating that viral respiratory infections in humans are affected by vitamin C levels. There is also evidence indicating that vitamin C may affect pneumonia.3 In particular, three controlled trials with human subjects reported a significantly lower incidence of pneumonia in vitamin C-supplemented groups,6 suggesting that vitamin C may affect susceptibility to lower respiratory tract infections under certain conditions. The possibility that vitamin C affects severe viral respiratory tract infections would seem to warrant further study, especially in light of the recent SARS epidemic.

References

1. Holmes, K. V. (2003). SARS-associated coronavirus. New England Journal of Medicine 348, 1948–51.
2. Leibovitz, B. & Siegel, B. V. (1981). Ascorbic acid and the immune response. Advances in Experimental Medicine and Biology 135, 1–25.
3. Hemilä, H. & Douglas, R. M. (1999). Vitamin C and acute respiratory infections. International Journal of Tuberculosis and Lung Diseases 3, 756–61.
4. Atherton, J. G., Kratzing, C. C. & Fisher, A. (1978). The effect of ascorbic acid on infection of chick-embryo ciliated tracheal organ cultures by coronavirus. Archives of Virology 56, 195–9.
5. Davelaar, F. G. & Bos, J. (1992). Ascorbic acid and infectious bronchitis infections in broilers. Avian Pathology 21, 581–9.
6. Hemilä, H. (1997). Vitamin C intake and susceptibility to pneumonia. Pediatric Infectious Diseases Journal 16, 836–7.
The British Society for Antimicrobial Chemotherapy

[p75213]

So it is the same drugs that others have been talking about for weeks now....Chloroquine and HIV drug (Ie probably Kaletra)

Seems like these drugs are the way to go at the moment if want to be sure to fight this virus.

Well luckily I got a prescription for Chloroquine to use as a last resort....don't like the side effects but guess it is better then death.

Korea has been using hydroxychloroquin in place of chloroquine. It is just as effective as chloroquine but with fewer side effects.

[lancebr]

I wouldn't say sham, but maybe evidence is not quite there yet due to lack of real interest.
SARS is a corona virus and

https://academic.oup...2/6/1049/731701

Vitamin C and SARS coronavirus
Harri Hemilä
Journal of Antimicrobial Chemotherapy, Volume 52, Issue 6, December 2003, Pages 1049–1050, https://doi.org/10.1093/jac/dkh002
Published: 01 December 2003
pdfPDF Split View Cite
Permissions Icon Permissions
Share
Keywords: ascorbic acid, pneumonia, severe acute respiratory syndrome
Issue Section: Correspondence
Sir,

Recently, a new coronavirus was identified as the cause of the severe acute respiratory syndrome (SARS).1 In the absence of a specific treatment for SARS, the possibility that vitamin C may show non-specific effects on severe viral respiratory tract infections should be considered. There are numerous reports indicating that vitamin C may affect the immune system,2,3 for example the function of phagocytes, transformation of T lymphocytes and production of interferon. In particular, vitamin C increased the resistance of chick embryo tracheal organ cultures to infection caused by an avian coronavirus.4 Studies in animals found that vitamin C modifies susceptibility to various bacterial and viral infections,3 for example protecting broiler chicks against an avian coronavirus.5 Placebo-controlled trials have shown quite consistently that the duration and severity of common cold episodes are reduced in the vitamin C groups,3 indicating that viral respiratory infections in humans are affected by vitamin C levels. There is also evidence indicating that vitamin C may affect pneumonia.3 In particular, three controlled trials with human subjects reported a significantly lower incidence of pneumonia in vitamin C-supplemented groups,6 suggesting that vitamin C may affect susceptibility to lower respiratory tract infections under certain conditions. The possibility that vitamin C affects severe viral respiratory tract infections would seem to warrant further study, especially in light of the recent SARS epidemic.

References

1. Holmes, K. V. (2003). SARS-associated coronavirus. New England Journal of Medicine 348, 1948–51.
2. Leibovitz, B. & Siegel, B. V. (1981). Ascorbic acid and the immune response. Advances in Experimental Medicine and Biology 135, 1–25.
3. Hemilä, H. & Douglas, R. M. (1999). Vitamin C and acute respiratory infections. International Journal of Tuberculosis and Lung Diseases 3, 756–61.
4. Atherton, J. G., Kratzing, C. C. & Fisher, A. (1978). The effect of ascorbic acid on infection of chick-embryo ciliated tracheal organ cultures by coronavirus. Archives of Virology 56, 195–9.
5. Davelaar, F. G. & Bos, J. (1992). Ascorbic acid and infectious bronchitis infections in broilers. Avian Pathology 21, 581–9.
6. Hemilä, H. (1997). Vitamin C intake and susceptibility to pneumonia. Pediatric Infectious Diseases Journal 16, 836–7.
The British Society for Antimicrobial Chemotherapy

 

Well I just don't understand why doctors are not open to alternative treatments nowadays,

 

Just because it might be a supplement or a herb that is not a prescription does not mean that

it might not be effective for something.

 

I think everything should be looked at to treat this virus and if a supplement or herb works then

why not try it.

 

.

 

[lancebr]

Here is an interesting article on some Chinese treatment for the virus:

 

https://www.elotus.o...967b9-136755105

 

 

.

[kurdishfella]

Anti-inflammatories may aggravate Covid-19, France advises

 

https://www.theguard...virus-infection

 

Listening to the body: Study examines the effects of fasting on infections

 

https://news.yale.ed...ting-infections

Edited by kurdishfella, 17 March 2020 - 08:13 AM.

[orion22]

best protection from coronavirus and to stay alive would have been to sell you re stocks 

[Adamzski]

Do people think that MK-677/HGH would help? There are papers on it boosting the immune system.

What about IV's of Glutathione? I'm thinking of getting back into a weekly IV.

[lancebr]

 

Anti-inflammatories may aggravate Covid-19, France advises

 

https://www.theguard...virus-infection

 

 

 

 

For people who might not be able to take Tylenol....I would assume aspirin would be fine?

 

.