Enteroviruses - revisited

[Jesse2233]

I wonder if a CBV4 cocktail of the most potent inhibitors would have synergistic effects

E.g.

1. 6 tabs Equilibrant
2. 4 tabs DHQ
3. 40mg Prozac
4. Arbidol
5. Raoulic acid
6. Neem
7. Emodin
8. DHEA

@Hip @halcyon ever tried anything like this?

 

[halcyon]

ever tried anything like this?

Not that specific combination, but my idea is to try something similar, plus viferon and/or isoprinosine.

 

[Hip]

ever tried anything like this?

Yes, before getting a blood test and determining which particular enterovirus I had, I took some cocktails of 10 or more anti-CVB supplements and drugs, but to no effect. But now I know that most things I took targeted the wrong virus.

I am currently toying with the idea of making liposomal DHQ, which should have much better bioavailability. The recommended ultrasonic cleaner for making liposomal vitamin C, etc, is this one, the iSonic P4810, a 135 Watt unit costing around $90. But I am trying to find something with similar power but cheaper.

 

[Jesse2233]

@Hip have you ever seen DHQ injections or IVs available. I imagine that would be ideal

@halcyon I'd be interested to know what your final combo looks like

 

[Hip]

@Hip have you ever seen DHQ injections or IVs available. I imagine that would be ideal

I've read DHQ injections are used in studies, but not quite sure how they work, as the problem is that DHQ solubility in water is poor, less than 1mg/ml. So to get our 500 mg dose of DHQ dissolved in water, that would require half a liter of water. You could inject that half liter by IV drip, but not really by syringe.

 

[Jesse2233]

I've read DHQ injections are used in studies, but not quite sure how they work, as the problem is that DHQ solubility in water is poor, less than 1mg/ml. So to get our 500 mg dose of DHQ dissolved in water, that would require half a liter of water. You could inject that half liter by IV drip, but not really by syringe.

Interesting, I wonder if a DHQ drip could be made by dissolving DHQ in saline and finding a willing ND or NP to infuse

 

[Hip]

IV drip provided by a medical professional is not going to be a convenient thing as a daily treatment taken on an indefinite basis. If DHQ works, you'd have to take it indefinitely I would think, else the virus will return (unlike oxymatrine, which for men, if it works, you only need to do a 6 month course and then your are done). And you would need a sterile source of DHQ, or a means of sterilizing the DHQ, in order to do this.

 

[Jesse2233]

Quite the predicament

Seems your lipsomal method is the best bet until a stronger dosage is manufactured

 

[JES]

@Jesse2233 That is an interesting cocktail. As I briefly mentioned in another thread, I plan to trial Fluoxetine at 40 mg, however, even that may not be enough to reach the EC50 concentration of this drug in the blood. I wish it had an effect in the lower doses, because SSRI side effects notoriously grow with dosage.

Another antidepressant that has activity against enteroviruses and CVB3 is Pirlindole, it's active against the same 2C viral protein as Fluoxetine. However, Pirlindole as a reversible MAO-A inhibitor could potentially be much easier to tolerate, depending on the dosage you need. I have trialed Moclobemide, which is another reversible MAO inhibitor, and the side effects were far less than with SSRI's. The problem for me is that Pirlindole is only available in Russia it seems, so I can't personally order it due to how customs work in my country, but it would be interesting to hear someone else with enterovirus infection trial it. Why do all the good antivirals seem to be restricted to the Russian market?

Edit: it seems Pirlindole could also have some effect against Multiple Sclerosis (source), so it seems like an interesting drug in many ways.

 

[Hip]

Another antidepressant that has activity against enteroviruses and CVB3 is Pirlindole

I have just been looking at the pirlindole study again, and as you indicate, pirlindole is potently antiviral for CVB3 and other enteroviruses. Specifically, the study says it is antiviral for enterovirus-B species, which includes coxsackievirus B and echovirus — the enteroviruses linked to ME/CFS.

So pirlindole will likely have antiviral activity against a range of coxsackievirus B and echovirus serotypes.


The study found that the EC50 concentration of pirlindole (in a cell line in vitro) was 7.7 μM. EC50 = the concentration which inhibits viral replication by 50%. And they found that there were no cytotoxic effects on the cells at concentrations as high as 100 μM.

In order to achieve a 7.7 μM concentration in your body tissues, I calculated (using this equation) that an oral pirlindole dose of 280 mg would be required. This dose would then reduce viral replication by 50%. In terms of antidepressant dosing of pirlindole, it says here that:

The initial dose is 50-100mg 2 times per day, the dose is gradually increased by 50mg to 150-300mg/day.

The maximum recommended dose is 400mg/day, divided into 2 parts. After the therapeutic effect has been achieved the treatment should be maintained during 2-4 weeks, after that the dose is gradually reduced.

So with pirlindole, you should get some antiviral effects with the maximum recommended antidepressant dose of 400 mg daily. Although it not an ideal l situation, as really you would want to go up to the 100 μM concentration which the study showed was still safe for cells in vitro, and will have much more potent antiviral effects. But 100 μM would correspond to an oral pirlindole dose of around 3.6 grams, which I guess is far too high, and this dose level may well have dangerous side effects.

So the situation with pirlindole seems similar to that of fluoxetine: you do get some antiviral effects at normal antidepressant doses, but the really strong antiviral effects are unfortunately only obtained at dose levels beyond the maximum antidepressant dose.

Pirlindole would probably be a little better tolerated than fluoxetine, though; and pirlindole has also been shown to be helpful for fibromyalgia.

The problem for me is that Pirlindole is only available in Russia it seems, so I can't personally order it due to how customs work in my country

Pirlindole costs £10 for 50 x 50 mg pills at the prescription-free rupharma.com (a reliable Russian pharmacy I used several times).

rupharma.com also has a sister company called mospharma.com who specialize in getting drugs to patients in countries whose customs are very strict, such as certain EU countries, as well as Australia and Canada.

 

[JollyRoger]

Treatment of Chronic Enterovirus Encephalitis With Fluoxetine in a Patient With X-Linked Agammaglobulinemia

http://www.pedneur.com/article/S0887-8994(16)30209-0/abstract

But why was there a success in the treatment of the girl with this chronic illness?

I can't get the full paper of this case but I don't think she was on a high dose i.v. antidepressants for several months.

 

[Hip]

The full paper (on Sci Hub) gives the dose used:

Fluoxetine was initiated as an adjuvant to IVIG at 0.5 mg/kg/day and was slowly titrated to 2.7 mg/kg/day.

This was for a 5 year old boy; but if we take an adult with a weight of 80 kg, that corresponds to a dose of 216 mg of fluoxetine a day, which is higher than the normal antidepressant dose. I think the very maximum antidepressant dose is 80 mg a day.

I am not sure how long the boy was given the fluoxetine treatment (it's not clear in the study), but I would guess that he stopped after a few weeks or months. But if you were to take that dose on a long term basis as an ME/CFS treatment, I imagine that there would be some side effects.

 

[JollyRoger]

This dosing
was selected in collaboration with our clinical pharmacy and extrapolated
from adult dosing guidelines given in vitro data which suggested that
inhibition of virus replication occurred at typical starting doses for
depression.

Maybe the low dose is enough.
I'm not an expert but did he get the drug oral?
Does an i.v. version of antidepressants even exist??
If I have to take the standard dosis for several years or the rest of my life in order to eradicate the virus and to live a normal life I would do it.
AND the levels of the drug in the brain are higher than in the blood (see picture; impossible for copy and paste).
A dose of 20-40mg is enough to reach 14mikroM in the brain.



Its also neuroprotective and can even build up some structures of the brain.

https://psychcentral.com/news/2013/...volved-in-creating-new-brain-cells/50116.html

A combination with oxymatrine and some herbals should beat em up..


And it's cheap

This is especially important given that PCR detection of enterovirus in the CSF is an insensitive test,9 and furthermore, immunosuppressive agents such as steroids or rituximab may
accelerate the progression of invasive enteroviral disease.

In some cases rituximab can be dangerous.
Maybe we need a brain biopsy prior a rituximab treatment.
Thid could explain some cases of deterioration after rituximab like the former soccer player olaf bodden.

 

[Hip]

inhibition of virus replication occurred at typical starting doses for depression.

That's correct, but you don't get a potent antiviral effect at those starting doses for depression (which are 20 mg of fluoxetine daily). You need higher doses to get a potent effect.

When you read antiviral studies, which are typically performed in human cell lines in vitro, the study will work out the concentration of the antiviral compound required to inhibit viral replication in the cell line by 50%. That's called the EC50 concentration.

One paper found that the EC50 for fluoxetine was a concentration of 3.36 μM.

 

[JollyRoger]

http://jamanetwork.com/journals/jamaneurology/article-abstract/2193882


dose of 20-40mg is enough to reach 14mikroM in the brain

 

[Jesse2233]

Here's my question, these treatments showed effectiveness for live active virema, but what about non-cytolytic intracellular EVs? Will any of these drugs be effective against stealth viruses in tissue?

 

[JollyRoger]

The treatment of the boy with With X-Linked Agammaglobulinemia was a chronic encephalitis.

 

[Jesse2233]

The treatment of the boy with With X-Linked Agammaglobulinemia was a chronic encephalitis.

But was chronic defined by mere duration of infection or had the virus changed state into the non-cytolytic form Dr Chia describes? It seems to have been rapidly destroying brain tissue leading to death which is not the generally course of ME

 

[JollyRoger]

In February 2014, at the age of 3.5 years he experienced
increasing difficulty with balance. Over the course of the next few months,
he continued to regress, and by May, 2014, he would speak only single
words and would take only a few steps independently. There was no
associated fevers or preceding viral symptoms noted with the onset.

Treatment was started at 6/27/15 so more than a year after the beginnings.
And he was immunosuppressive.

When does this process happens of non cytolitic form?

3months of interferon and a 20mg/day lifelong dosis would be the curing maybe.

 

[Hip]

dose of 20-40mg is enough to reach 14mikroM in the brain

That's very interesting! That would then explain why oral fluoxetine was so effective for the 5 year old boy with the enterovirus encephalitis brain infection mentioned earlier: because fluoxetine concentrates in the brain, at levels up 20 times higher than found in the blood, according to the paper you cited (full paper here).

So if ME/CFS were caused by an enterovirus infection of the brain, fluoxetine might potentially be a very effective antiviral treatment. But we know that Dr Chia has been experimenting with fluoxetine for enterovirus-associated ME/CFS, and as far as we know, he has not reported any major successes with fluoxetine.

So that suggests either: (1) ME/CFS is not generally caused by chronic enterovirus infections of the brain; or (2) as @Jesse2233 alludes to, fluoxetine is no good at fighting the non-cytolytic form of the enterovirus found in the chronic low level enterovirus infections of ME/CFS.

The mechanism of fluoxetine's antiviral action on enteroviruses is not known, but it may involve fluoxetine's effects on the enteroviral 2C protein, which then inhibit viral replication. The other antidepressant discussed earlier, pirlindole, also targets 2C. I am guessing this will have some effect against non-cytolytic enteroviruses.

Here's my question, these treatments showed effectiveness for live active virema, but what about non-cytolytic intracellular EVs?

That's really a question for Dr Chia, or some other enterovirus expert: what sort of antiviral mechanisms best target non-cytolytic enteroviruses? I generally assume that viral genome replication inhibitors will work for both lytic and non-cytolytic enteroviruses, whereas entry inhibitor or uncoating inhibitor mechanisms will only work for lytic enteroviruses. And of course any antiviral that boosts interferon alpha will I think fight non-cytolytic enteroviruses, because interferon alpha activates the intracellular immune response which targets such non-cytolytic infections.

But in any case, you always get lytic and non-cytolytic enterovirus infections occurring together, feeding off each other, so even if you just inhibit the lytic infection, that may indirectly inhibit the non-cytolytic infection to some degree as well.

I touch this lytic versus non-cytolytic antivirals a bit in this earlier post.