31 replies to this topic

[Turnbuckle]

Can mito fusion stop Covid-19?

 

It’s a simple idea:

 

1. Some coronaviruses fill cells with virions, then manipulate mito morphology to drive apoptosis, thereby liberating virions into intercellular space.

2. Mito fission is required (but not sufficient) for apoptosis.

3. Stearic acid drives mito fusion and may prevent apoptosis, thus slowing down the viral growth rate and giving the body’s immune system time to build up antibodies.

 

References:

 

[1] Transmissible Gastroenteritis Coronavirus Induces Programmed Cell Death in Infected Cells through a Caspase-Dependent Pathway

In conclusion, the present study provided evidence that TGEV [a porcine coronavirus] can act as a true apoptotic inducer in cultured cells. The available data point to oxidative stress as a possible trigger for TGEV-induced apoptosis. However, owing to the recognized complexity of this biological process, additional investigations are needed to substantiate this view. An important finding is that TGEV-induced cell death could be efficiently prevented by a caspase inhibitor, consistent with the notion that apoptosis potentially represents a major mechanism in the viral CPE. Accordingly, it would be interesting to examine in vivo whether PCD plays a role in the pathogenesis of TGEV infection. Finally, TGEV is, to our knowledge, the first coronavirus reported to trigger direct apoptosis in infected cells. It would be worth pursuing investigations to determine whether such a property could be shared by other members of this family.

https://www.ncbi.nlm...cles/PMC110052/

 

[2] Regulation of mitochondrial fission and apoptosis by the mitochondrial outer membrane protein hFis1

Mitochondrial fission is a highly regulated process mediated by a defined set of protein factors and is involved in the early stage of apoptosis.

https://jcs.biologis...ent/118/18/4141

 

[3] Dietary stearic acid regulates mitochondria in vivo in humans

We show here that C18:0 ingestion rapidly and robustly causes mitochondrial fusion in people within 3 h after ingestion

https://www.ncbi.nlm...les/PMC6081440/

 

Caveat: Viruses don’t all work the same way. Some drive mitochondria to fission but prevent apoptosis. These might also be slowed down by fusion —

 

CSFV induced mitochondrial fission and mitophagy to inhibit apoptosis

Classical swine fever virus (CSFV), which causes typical clinical characteristics in piglets, including hemorrhagic syndrome and immunosuppression, is linked to hepatitis C and dengue virus. Oxidative stress and a reduced mitochondrial transmembrane potential are disturbed in CSFV-infected cells. The balance of mitochondrial dynamics is essential for cellular homeostasis. In this study, we offer the first evidence that CSFV induces mitochondrial fission and mitophagy to inhibit host cell apoptosis for persistent infection. The formation of mitophagosomes and decline in mitochondrial mass relevant to mitophagy were detected in CSFV-infected cells. CSFV infection increased the expression and mitochondrial translocation of Pink and Parkin.

https://www.ncbi.nlm...les/PMC5503620/

 

Viruses that bud off infected cells may not respond to fusion.

 

Edited by Turnbuckle, 28 March 2020 - 07:31 PM.

[Robert Magnuson]

Please see this petition at Change.org

 

http://chng.it/nBGJZxYQHx

 

Title: China is Resolving Coronavirus with Vitamin C Injections. Demand the Same for the USA! 

[Ken Mark]

Inhibiting fusion promotes apoptosis.

https://www.ncbi.nlm...les/PMC2732420/

[stephen_b]

Inhibiting fusion promotes apoptosis.

https://www.ncbi.nlm...les/PMC2732420/

 

Do you mean inhibiting fission?

 

Apoptosis, or programmed cell death, begins with the breakdown of mitochondria into smaller pieces. (Wikipedia)

[yz69]

Hi Turnbuckle,

check this out https://papers.ssrn....ract_id=3581388

 

Oral nicotinamide mononucleotide (NMN) with boosters may naturally trigger anti-inflammation immune systems able to arrest and reverse cytokine storm. A COVID-19 positive case is described with a strong temporal relationship between NMN cocktail use and clinical improvement - more remarkably this case exhibits an unusually rapid and thorough clinical turnaround. Oral NMN with boosters deserve further study in COVID-19 associated cytokine storm.

Large dose of NMM, which may boost mito fission and apoptosis, may actually a good thing for treating covid19? 

[Turnbuckle]

Hi Turnbuckle,

check this out https://papers.ssrn....ract_id=3581388

Large dose of NMM, which may boost mito fission and apoptosis, may actually a good thing for treating covid19? 

 

 

Interesting. But it took 5 days after the first dose before her fever broke. By contrast, I've woken up with flu like symptoms, and a couple of hours after a dose of stearic acid, the symptoms faded and disappeared. Covid and influenza operate the same way, taking control of apoptosis to spread the viral particles.

[yz69]

Found this article

https://www.scienced...167488915000099

 

 

from table 2

looks like SARS coronavirus operate on the fusion mode, opposite to Influenza A virus

[Turnbuckle]

Found this article

https://www.scienced...167488915000099

 

 

from table 2

looks like SARS coronavirus operate on the fusion mode, opposite to Influenza A virus

 

 

ORF-9b's effect on mitochondria is apparently to block the immune response by elongating mitochondria, and when it turns off, other ORF proteins drive cells to apoptosis, thus stearic acid may override that.

 

The virus genome encodes eight accessory proteins designated ORF-3a, 3b, 6, 7a, 7b, 8a, 8b and 9b. Several have identified functions. ORF-3a triggers cellular apoptosis, ORF-7a activates nuclear factor-κB (NF-κB), ORF3b upregulates the expression of several cytokines and chemokines, ORF-6 reduces interferon production; ORF-8a triggers cellular apoptosis, and ORF-8b induces cellular DNA synthesis (12). 

https://www.ncbi.nlm...les/PMC7098028/

 

 

Finally, transient ORF-9b expression led to a strong induction of autophagy in cells.

https://www.ncbi.nlm...les/PMC4179872/

 

 

[Nate-2004]

Here's a paper (not yet peer reviewed) claiming NMN administration actually reversed the "cytokine storm" in one covid-19 patient.

 

https://papers.ssrn....iAiUm1kTlhaIn0=

[Hip]

Some coronaviruses fill cells with virions, then manipulate mito morphology to drive apoptosis, thereby liberating virions into intercellular space.

 

I don't think any viruses escape from the cell by inducing apoptosis. The way viruses burst out of the cell is by lysis, where the cell wall is ruptured and the viruses escape. The cell is destroyed in the process. 

[Nate-2004]

I don't think any viruses escape from the cell by inducing apoptosis. The way viruses burst out of the cell is by lysis, where the cell wall is ruptured and the viruses escape. The cell is destroyed in the process. 

 

 

 

Lysis

Description Lysis is the breaking down of the membrane of a cell, often by viral, enzymic, or osmotic mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a lysate. Wikipedia

[Hip]

Lysis

Description Lysis is the breaking down of the membrane of a cell, often by viral, enzymic, or osmotic mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a lysate.

 

Yes, that's lysis, and it makes a bit of mess, as the contents of the cell are spewed out. 

 

Whereas apoptosis is an ordered and controlled event, where the cell is dissembled according to a preprogramed process.

[Turnbuckle]

I don't think any viruses escape from the cell by inducing apoptosis. The way viruses burst out of the cell is by lysis, where the cell wall is ruptured and the viruses escape. The cell is destroyed in the process. 

 

 

See the first reference in the opening post.

[Mr Spock]

Hi,

 

What form of stearic acid should you use,in the UK what's available is only for external use; candle making, lotions etc

[Turnbuckle]

Hi,

 

What form of stearic acid should you use,in the UK what's available is only for external use; candle making, lotions etc

 

 

Glycerol monostearate is available in the UK. It is digested much faster, and thus I would start with a low dose--under one gram--as some with hypertension may see BP rise faster than antihypertensives can bring it down, and thus can be dangerous for those people. A BP monitor is highly advisable, at least at first. An effective dose for fusion will be 1-5 grams, and the half life is around 11 hours. It can be stirred into hot foods or drink.

 

Mango butter is another option. It is a triglyceride with 40-45% stearic acid.

Edited by Turnbuckle, 07 May 2020 - 09:48 PM.

[Mr Spock]

Glycerol monostearate is available in the UK. It is digested much faster, and thus I would start with a low dose--under one gram--as some with hypertension may see BP rise faster than antihypertensives can bring it down, and thus can be dangerous for those people. A BP monitor is highly advisable, at least at first. An effective dose for fusion will be 1-5 grams, and the half life is around 11 hours. It can be stirred into hot foods or drink.

 

Mango butter is another option. It is a triglyceride with 40-45% stearic acid.

 

I actually have high BP and on Ramipril ( ACE inhibitor) but on top I 've the covid virus; symptoms have been breathlessness and fatigue. Tomorrow, saturday will be my 3rd week since symptoms started.

 

Have excluded any other heart related issues as seen a cardiologist who had echo of the heart done and ECG.

 

Under the circumstances, should I take it? would mango butter be any safer?

 

Thanks

[Turnbuckle]

I actually have high BP and on Ramipril ( ACE inhibitor) but on top I 've the covid virus; symptoms have been breathlessness and fatigue. Tomorrow, saturday will be my 3rd week since symptoms started.

 

Have excluded any other heart related issues as seen a cardiologist who had echo of the heart done and ECG.

 

Under the circumstances, should I take it? would mango butter be any safer?

 

Thanks

 

 

Nothing in this thread should be construed as medical advice. This hasn't been tried for coronavirus, and the whole site is primarily about life extension, with a lot of self experimentation. That said,  mango butter should be safer for those with hypertension. I suggest you mix it into a hot beverage and use it twice a day. Start off with half a teaspoon, and if BP is okay, you could ramp it up to one and then two teaspoons, if you are a male of average weight. One liquid teaspoon of mango butter is about 4.5 grams, which will deliver 1.8-2 grams of stearic acid.

 

The taste of mango butter is mild, while stearic acid has almost no taste.

 

If you try this, please let us know the results.

Edited by Turnbuckle, 08 May 2020 - 12:37 PM.

[Mr Spock]

Just ordered some; will do.

[Hip]

See the first reference in the opening post.

 

Interesting. Inducing apoptosis appears to be something unique to coronaviruses. Normally, viruses escape from infected cells by lysis (rupturing the cell membrane, so that the cell contents burst of the cell). So the death of cells is caused by lysis.

 

But it appears that it is not coronavirus-infected cells which undergo apoptosis: rather, coronavirus-infected cells will release soluble factors that cause nearby unifected cells to undergo apoptosis. This paper says:

Numerous coronaviruses ... have been shown to induce apoptosis in non‐infected cells indirectly via the release of soluble cell‐death mediators from neighbouring infected cells.

 

 

 

 

SARS triggers apoptosis (in Vero cells), but there's not much in vitro evidence yet regarding whether or not SARS-CoV-2 triggers apoptosis, but this paper suggests it does. If so, it might explain why SARS-CoV-2 causes so much damage to lungs. 

 

It is not clear to me whether this apoptosis is just an unfortunate side effects of coronavirus infection, or whether it has any useful purpose for the virus, in terms of virus survival and replication. 

[Turnbuckle]

 

 

But it appears that it is not coronavirus-infected cells which undergo apoptosis: rather, coronavirus-infected cells will release soluble factors that cause nearby unifected cells to undergo apoptosis. This paper says:

 

 

 

I don't read it that way. I read that apoptosis can be induced in neighboring cells by release of soluble cell‐death mediators from infected cells, but the paper doesn't say that the infected cells don't undergo apoptosis as well. In fact, the first sentence of the summary states--

 

Both apoptosis and necrosis have been observed in cells infected by various coronaviruses, suggesting that the regulation of cell death is important for viral replication and/or pathogenesis. 

 

[Hip]

I don't read it that way. I read that apoptosis can be induced in neighboring cells by release of soluble cell‐death mediators from infected cells, but the paper doesn't say that the infected cells don't undergo apoptosis as well. In fact, the first sentence of the summary states--

 

I could not find any evidence for coronavirus causing apoptosis in infected cells, only in nearby uninfected cells.

 

I am not sure if apoptosis would allow newly-created virions to escape from a virally-infected cell, as apoptosis is an ordered shut down and ordered deconstruction of a cell. So it's likely that any new virions in the cell would be destroyed by apoptosis.

 

In fact normally viruses try hard to prevent apoptosis, because apoptosis of infected cells triggered by the immune system is a means to fight the infection. So if coronavirus induced apoptosis in the cells it infected, this virus might be shooting itself in the foot.

 

Maybe there is some advantage for coronavirus to trigger apoptosis in cells nearby the infected cell, but it's not clear what this advantage might be. Alternatively, maybe this nearby apoptosis occurs by accident, as a side effect, and is not actually useful for the virus.

 

This paper says that the SARS coronavirus induces apoptosis by secreting the coronavirus 7a protein, as well as other apoptosis-inducing proteins, like the 3C-like protease. I am thinking that perhaps these proteins have some other purpose which benefits the virus, and the apoptosis in neighboring cells caused by these proteins might just be a side effect.

 

 

 

In any case, if apoptosis is induced by SARS-CoV-2, and if this is a major contributor to the lung damage caused by this virus, then inhibition of apoptosis might be beneficial in COVID-19.

Edited by Hip, 18 May 2020 - 03:53 PM.

[Turnbuckle]

 

This paper says that the SARS coronavirus induces apoptosis by secreting the coronavirus 7a protein, as well as other apoptosis-inducing proteins, like the 3C-like protease. I am thinking that perhaps these proteins have some other purpose which benefits the virus, and the apoptosis in neighboring cells caused by these proteins might just be a side effect.

 

 

 

Likely it enhances coughing and thus the spread of the virus. Reducing apoptosis of either infected or uninfected cells should reduce the severity of the response and give the body more time to fight it.

[Mr Spock]

Nothing in this thread should be construed as medical advice. This hasn't been tried for coronavirus, and the whole site is primarily about life extension, with a lot of self experimentation. That said,  mango butter should be safer for those with hypertension. I suggest you mix it into a hot beverage and use it twice a day. Start off with half a teaspoon, and if BP is okay, you could ramp it up to one and then two teaspoons, if you are a male of average weight. One liquid teaspoon of mango butter is about 4.5 grams, which will deliver 1.8-2 grams of stearic acid.

 

The taste of mango butter is mild, while stearic acid has almost no taste.

 

If you try this, please let us know the results.

 

So I obtained the mango butter here in the UK,and this sample has very little,if any,taste. It's hard at room temperature.

 

If I did have the virus, then I started taking it way past when I first became infected, and have concluded it's a bit late for me to be taking it now,although I still have breathlessness.

 

But it's in the cupboard for next time..

[Empiricus]

First, some background.  My symptoms were fairly severe, but apart from several telemedicine consults, I was never professionally examined, tested, or treated.   

 

My experience with the "plague de jour" could be divided into four phases:

I. Mild "shortness of breath" and "exercise fatigue" phase lasting about 2 week, resolving 100%.  

II. Debilitating shortness of breath and whole body weakness, heaviness in the chest, and fatigue. These symptoms left me bedridden for 2 months, followed by brief partial recovery.

III. Another couple months with a really bad cough, worse chest pains than before, debilitating fatigue, occasional shortness of breath. During this time I puttered around the apartment. I began going on short walks, but these left me totally exhausted.

IV. Months where I gained strength, rapidly recover, but still experience occasional bouts of sharp chest pains. 

 

Aside from diet, exercise, and sun exposure, my initial go-to treatment for phase IV symptoms ("bouts of sharp chest pains") has been nattokinase.  I've been operating under the assumption tiny blood clots were responsible for the pains.  Both inadvertently and deliberately, I've tested this theory a number of times by consuming K2.  Soon after I consume K2, the chest pains tend to occur or worsen, leading me to believe worsening pain is cause by an exacerbation of clotting, which K2 would be expected to aggravate. Nattokinasse, of course, should have the opposite effect, and it has consistently brought me relief.

 

On discovering this Turnbuckle thread in July, I started experimenting with GMS (glycerol monostearate).  I've been taking it on and off for 2 months, and I am now confident that GMS also contributes to relief of chest pain.   Just recently, I felt the chest pain coming back strong with some flu symptoms and feared a full-blown relapse might be at hand.  I began taking 2 grams of GMS every 8 hours, and the disturbing, escalating symptoms went away.  

 

The combination of nattokinase and GMS seems to be highly effective, but I have found relief of chest pain symptoms without the addition of nattokinase.  For example, on one occasion, a single 15 gram dose of GMS resolved the chest pains for many days.   

 

For a long time I believed GMS might have the unfortunate side effect of hair shedding, but now I attribute that to some whey powder ("mineral whey") I had started taking around the same time in large amounts but have since discontinued. 

 

Incidentally, I have taken an enormous number of supplements over the course of the past year (even by longevity standards).  I have not experienced any notable relief with fission promoters such as niacinamide or NMN.  At some point I will likely try to re-introduce them to balance out all the fusion. 

 

[Turnbuckle]

 

The combination of nattokinase and GMS seems to be highly effective, but I have found relief of chest pain symptoms without the addition of nattokinase.  For example, on one occasion, a single 15 gram dose of GMS resolved the chest pains for many days.   

 

 

 

Those with hypertension should be leery of GMS, as that much could kill you if you via a stroke. Mango butter appears to be much safer.

[Empiricus]

Those with hypertension should be leery of GMS, as that much could kill you if you via a stroke. Mango butter appears to be much safer. 

 

 

Indeed. As advised by Turnbuckle, before taking GMS on a regular basis, I did rounds of blood pressure monitoring to insure that the GMS wasn't raising my blood pressure.  As I reported in Turnbuckle's mitochondria protocol, it wasn't.  

 

In the past 2 weeks, I have stopped taking nattokinase, and GMS is now my go-to treatment when I experience signs of chest discomfort.  I generally take about 5 grams of powder.  I find myself reaching for it every couple days.   I melt the GMS together with chunk of 80% dark chocolate then add milk.  I believe GMS even improves the taste of hot chocolate!

 

Nevertheless, Nattokinase is amazing stuff.  A scar on my leg mostly disappeared during the three months I took it regularly, but it seemed to make my sweat smell strange.  

Edited by Empiricus, 27 September 2020 - 08:08 AM.

[Empiricus]

Time for an update.  I discontinued the nattokinase, but continued taking the stearic acid as GMS. Periodic chest pains, the main lingering symptom, became less noticeable through September to the extent that I no longer experienced jabs of chest "pain" but only occasional chest discomfort.  I thought I was feeling sufficiently well to introduce fission, so I did a round of Turnbuckle's Exercise Like a Girl protocol.  

 

First day I felt great (steep hike following Ingestion of 2G niacinamide and 2G of roboside).  

 

The experience was so refreshing that I decided to go for a second round the next day.  On the following day I took the N+R, but this time after exercising, I took 1 gram of NMN.  Within hours I got bad chest pains for the first time in a month.  

 

After 10 days of daily GMS plus a few doses of nattokinase I felt sufficiently recovered to repeat a variation of turnbuckle's N+R-prior-to-exercise protocol, this time leaving out my previous addition of an NMN finale (as I strongly suspected the NMN had caused the trouble), but this time including 1 gram of jiaogulan extract for AMPK.  Nevertheless, once again, the sharp chest pains returned the same day.  In addition, I experienced a short spell of low-level feverishness.  

 

Since my usual 5 ml/day of GMS wasn't cutting it, the next evening I took 20 ml of GMS powder.*  That evening I also took 20 ml of agaricus bleizi and 20 ml of liver powder -- two of the supplements I had success with at previous stages of the illness and before turning to natokinasse and GMS. By morning I felt well again. 

 

I've ordered some mango butter.  When it arrives I will try substituting it for the GMS.  

 

* Thirty minutes after taking 20 ml of GMS I took a blood pressure reading.  It was within my normal (healthy) range.   

 

Edited by Empiricus, 15 October 2020 - 10:26 AM.

[Turnbuckle]

Time for an update.  I discontinued the nattokinase, but continued taking the stearic acid as GMS. Periodic chest pains, the main lingering symptom, became less noticeable through September to the extent that I no longer experienced jabs of chest "pain" but only occasional chest discomfort.  I thought I was feeling sufficiently well to introduce fission, so I did a round of Turnbuckle's Exercise Like a Girl protocol.  

 

First day I felt great (steep hike following Ingestion of 2G niacinamide and 2G of roboside).  

 

The experience was so refreshing that I decided to go for a second round the next day.  On the following day I took the N+R, but this time after exercising, I took 1 gram of NMN.  Within hours I got bad chest pains for the first time in a month.  

 

After 10 days of daily GMS plus a few doses of nattokinase I felt sufficiently recovered to repeat a variation of turnbuckle's N+R-prior-to-exercise protocol, this time leaving out my previous addition of an NMN finale (as I strongly suspected the NMN had caused the trouble), but this time including 1 gram of jiaogulan extract for AMPK.  Nevertheless, once again, the sharp chest pains returned the same day.  In addition, I experienced a short spell of low-level feverishness.  

 

Since my usual 5 ml/day of GMS wasn't cutting it, the next evening I took 20 ml of GMS powder.*  That evening I also took 20 ml of agaricus bleizi and 20 ml of liver powder -- two of the supplements I had success with at previous stages of the illness and before turning to natokinasse and GMS. By morning I felt well again. 

 

I've ordered some mango butter.  When it arrives I will try substituting it for the GMS.  

 

* Thirty minutes after taking 20 ml of GMS I took a blood pressure reading.  It was within my normal (healthy) range.   

 

 

If you did have covid and stearic acid stopped it, then you still have cells full of covid viruses that haven't yet detonated. So perhaps the best plan would be to slowly lower your stearic acid intake, and not try to do it all at once by upping NAD+ levels.

[Turnbuckle]

Yesterday Venezuela announced that they had found a derivative of ursolic acid that defeated the covid virus. (Within hours, the Trump admin responded by threatening to bomb them.)

 

President Nicolas Maduro said Venezuelan scientists have isolated a molecule that inhibits the Covid-19 virus and will ask the World Health Organization to evaluate its possible use on a global scale. The active ingredient is a derivative of ursolic acid from a plant and non-toxic to humans, Maduro said in an appearance on state television Sunday. Six months of research at the government-backed IVIC scientific institute led to the discovery, he said.

https://www.bloomber...hibits-covid-19

 

 

 

Toxicity of ursolic acid (UA) is known to be low in rats --

This study indicates that oral dosing of UA for 90 consecutive days does not lead to toxic effects at any of the doses. Therefore, the NOAEL for UA is likely to be higher than 1000 mg/kg/day.

https://www.scienced...214750020301013

 

 

 

UA is found in apple peels and is sold as an aid for muscle building. There was previously evidence it could inhibit coronaviruses --

The study provides a basic foundation and suggests that the three phytochemicals, viz. ursolic acid, carvacrol and oleanolic acid could serve as potential inhibitors in regulating the Mpro protein’s function and controlling viral replication.

https://www.ncbi.nlm...les/PMC7284142/

 

 

 

Thus combining mito fusion and UA supplementation might constitute an inexpensive OTC treatment anyone could use today.

 

 

Edited by Turnbuckle, 27 October 2020 - 11:48 AM.

[Hip]

Ursolic acid has some safety question marks hanging over it: 

 

Ursolic acid damages DNA: https://pubmed.ncbi....h.gov/21703625 

 

However, other studies have shown it also has a protective effect against oxidative DNA damage: https://pubmed.ncbi....ih.gov/20659486

 

 

In any case, the bioavailability of ursolic acid is very low, at around 1%. So although you get around 50 mg of ursolic acid in an apple peel, very little is actually absorbed, which may be a good thing if there are DNA damage issues.

 

I've looked into ursolic acid previously, as it has an antiviral effect against coxsackievirus B, which is the virus behind the chronic fatigue syndrome I suffer from. However, I became concerned about its possible DNA damaging effects.

 

 

 

 

 

Edited by Hip, 27 October 2020 - 02:14 PM.