Enteroviruses - revisited

[Hip]

ave you ever tried Ibudilast?

I haven't, but there is a brief report here.

 

[Jesse2233]

@Hip any leads for a good source of DHQ? Can't seem to find it without Vitamin C

Also raoulic acid

 

[Hip]

@Hip any leads for a good source of DHQ? Can't seem to find it without Vitamin C

I was using this dihydroquercetin (DHQ) product: Swanson Ultra Russian Rejuvenator | 60 Capsules - £14.35

I believe this form of DHQ is a molecular complex of dihydroquercetin and vitamin C (based on the Russian drug Ascovertin). I am not sure why they complex DHQ with C, but it may be to enhance DHQ absorption and bioavailability.

DHQ by the kilo: http://www.balinvest.lv/shop/

I understand from @halcyon that Dr Chia is now recommending DHQ for antiviral purposes. DHQ is a potent antiviral, as effective as ribavirin for coxsackievirus B4.

However, the problem with DHQ is that its oral absorption is only a measly 0.49% (see this study; note that DHQ is also called taxifolin).

Though I read that oral DHQ absorption goes up to 36% if dissolved in lipid solution. So when I took my DHQ, I dissolved the powder in heated coconut oil first. I am hoping that will get me 36% absorption (though one would really need to explore which oils or lipids are best suited to promoting DHQ oral absorption).

From the CVB4 study, I worked out you would want a human injectable dose of around 500 mg DHQ daily; this is equivalent to the study's intraperitoneal dosing protocol for mice. (This is based on the lower dose of 75 mg/kg used in the study: to convert mouse to human doses, you need to divide by 12.3, which gives you a human dose of 6 mg/kg. Then for an 85 kg human, this gives an injectable dose of around 500 mg).

Now if we assume DHQ has a 36% absorption in a lipid solution (like coconut oil), that corresponds to a human oral dose of around 1400 mg of DHQ in lipid solution.

My problem with DHQ is that even at oral doses of just 180 mg, DHQ causes me a lot of brain overstimulation. This overstimulation I think is likely due to adenosine receptor antagonism: quercetin is an adenosine receptor antagonist, and I am guessing DHQ, which is related to quercetin, may be also. The stimulant caffeine works by adenosine receptor antagonism.

The brain overstimulation was too strong for me, so I stopped taking DHQ. I am trying to find a workaround for this, to prevent the adenosine receptor antagonism and the resultant overstimulation caused by DHQ.

 

[Jesse2233]

Thanks for all that @Hip

Any chance dissolving the DHQ in heated coconut oil destroys it due to the heat? And what's the best way to mix it in?

Also any place I could buy roulic acid?

 

[Hip]

Any chance dissolving the DHQ in heated coconut oil destroys it due to the heat?

I am not sure; it's possible. I did not heat it very much, maybe around 100ºC. But the heating may not even be necessary: just mixing DHQ in oil at room temperature may suffice. The trouble is, there is no way to determine how much DHQ is being absorbed in the gut.

Also any place I could buy roulic acid?

I have looked high and low for a supplier of raoulic acid, which is a potent antiviral for CVB3, CVB4, rhinovirus and enterovirus 71. However, I could not find a source for raoulic acid, nor the plant that it comes from, Raoulia australis (although you can buy Raoulia australis seeds, if you want to grow your own).



Another very interesting potent and broad-spectrum anti-enteroviral compound is OSW-1, which comes from the bulbs of the plant Ornithogalum saundersiae.

OSW-1 is a potent anti-enteroviral in very minute amounts: according to the study, IC50 antiviral concentrations for OSW-1 are in the range of 2.4 and 9.4 nM, and there were no cytotoxic effects at 100 nM concentrations. So a 100 nM concentration would be a safe, non-toxic dose level (going higher may start to cause cytotoxic damage to cells).

By my calculation, that 100 nM concentration corresponds to an oral dose of just 3 mg of OSW-1, assuming 100% bioavailability. So then using a dose of 3 mg daily, even just 1 gram of OSW-1 would last you for many months.


I have not been able to find a retail source of OSW-1, but you can find many wholesale suppliers of OSW-1 online (these will usually only sell to businesses, not individuals). Some wholesale suppliers are here.

Wholesale suppliers online sell OSW-1 by the kilogram, but I am not sure of the price per kilo. If you want to search for suppliers, the CAS number for OSW-1 is 145075-81-6.

 

[Jesse2233]

Thanks again @Hip

A few more questions

1. So even if I mix in a specific amount of DHQ with the coconut oil, it's not all guaranteed to be absorbed? Would a good strategy to start low and slow and build to intolerance?

2. If I grew my own Raoulia, which part of the plant would I harvest and how would I prepare / dose it?

3. Is a US wholesale supplier of OSW-1 best?

 

[Hip]

1. So even if I mix in a specific amount of DHQ with the coconut oil, it's not all guaranteed to be absorbed? Would a good strategy to start low and slow and build to intolerance?

If you look at the study, it says that:

0.1g of taxifolin [= DHQ] was dissolved in 10 ml of Labrasol at 35ºC in an ultrasound bath (Sapfir, Russia) for 40 min.

So Labrasol® is the lipid solution they used. I substituted with coconut oil, but I am not sure how this compares to Labrasol.

Then for every 100 mg of DHQ you want to take, you need 10 ml of Labrasol (or 10 ml of coconut oil, assuming you can substitute). Plus they placed this in an ultrasound bath, presumably to break up any large particles of DHQ, and to promote dissolving. I don't have an ultrasound bath (but you can buy ultrasonic jewelry cleaner baths on eBay for as little as £20, which I think are the same thing).

2. If I grew my own Raoulia, which part of the plant would I harvest and how would I prepare / dose it?

The study says that they used the aerial parts of the plant to extract the raoulic acid, and then they provide the extraction procedure. I am not sure if you can instead just eat the plant (as maybe the plant might be toxic).

(I take it that you are aware you can read the full papers on Sci-Hub?)

Is a US wholesale supplier of OSW-1 best?

I would prefer Chinese wholesalers, as they are likely cheaper. But unless you are a company, with a company website or some other evidence that you are a business, they will likely not reply to you. I've tried dealing with wholesalers before in order to buy other compounds, and they tend not to reply to individuals.

 

[Jesse2233]

@Hip thanks, impressed and grateful for your depth of knowledge, organization, and willingness to help

 

[Jesse2233]

@halcyon do you know how Chia admisters his DHQ?

 

[Hip]

@Hip thanks, impressed and grateful for your depth of knowledge, organization, and willingness to help

A pleasure to help. But I always view it as a joint effort involving all of us on the forum, sharing ideas and info in the search for solutions.

 

[halcyon]

@halcyon do you know how Chia admisters his DHQ?

He didn't recommend any specific brand or dose. I already had Russian Rejuvinator on hand so just started taking that.

 

[Jesse2233]

Hey @Hip

What's your source for oseltamivir being effective against CBV4? The paper linked went somewhere else, and I couldn't find anything on Google

 

[Hip]

What's your source for oseltamivir being effective against CBV4? The paper linked went somewhere else, and I couldn't find anything on Google

That link is actually correct: if you look at Table 1 of the full paper on Sci Hub, you see that oseltamivir (Tamiflu) is antiviral for CVB4 (in vitro, in Vero cells), with a selectivity index (aka therapeutic index, TI) of 29.75.

For CVB3, the selectivity index of oseltamivir is 79.42, which means a stronger antiviral effect.


Oseltamivir is pretty expensive though, at around $8 per each 75 mg capsule. Although buy-pharma sell a much cheaper generic.

I keep meaning to try oseltamivir for say 1 month.

 

[Jesse2233]

Thanks for pointing that out, very interesting. Seems that it's the only pharmaceutical antiviral for CBV4. Is it likely to work on both chronic and acute infections?

 

[Hip]

Seems that it's the only pharmaceutical antiviral for CBV4. Is it likely to work on both chronic and accuse infections?

That study only mentions oseltamivir in passing, and does not examine the antiviral mechanism against CVB, and without knowing this mechanism, it is hard to say whether it will work equally well on acute and chronic infections.

Though this brief letter on the efficacy of oseltamivir for hand foot and mouth disease (usually caused by CVA or enterovirus 71) speculatively suggests that oseltamivir's inhibition of neuraminidase, an enzyme which breaks down sialic acid, prevents the loss of the protective sialic acid on the cell surface, thereby preventing viral entry:

A lipophilic side chain of the active drug binds to the virus enzyme [neuraminidase], blocking its ability to cleave sialic acid residues on the surface of the infected cell resulting in an inability to release progeny virions.

Usage of sialic acid is a common feature of at least three different viruses with pandemic potential: Coxsackie Virus A24, Enterovirus 70, and influenza A virus. This sialic acid link could be a common pathway by which oseltamivir helps in HFMD.

If true, this would make oseltamivir a viral entry inhibitor for enterovirus, which probably works better for acute enterovirus infections rather than chronic ones.


Itraconazole will most likely also work for CVB4. This is because this drug has been shown to have broad-spectrum antiviral effects against diverse enteroviruses, including CVA16, CVB3, enterovirus 71 and even poliovirus 1 (polioviruses are also enteroviruses). So because itraconazole works across the board for these diverse enterovirus types, one would guess it may well work for all the CVBs.

Itraconazole targets the 3A enterovirus protein — which is a critical component in viral replication.

@halcyon, I am not sure if the 3A protein is present in echovirus; but if it were, then itraconazole might be good for your echovirus infections as well.

 

[Jesse2233]

Itraconazole will most likely also work for CVB4. This is because this drug has been shown to have broad-spectrum antiviral effects against diverse enteroviruses, including CVA16, CVB3, enterovirus 71 and even poliovirus 1 (polioviruses are also enteroviruses). So because itraconazole works across the board for these diverse enterovirus types, one would guess it may well work for all the CVBs.

Itraconazole targets the 3A enterovirus protein — which is a critical component in viral replication.

@halcyon, I am not sure if the 3A protein is present in echovirus; but if it were, then itraconazole might be good for your echovirus infections as well.

Interesting, I will add Itraconazole to my list of questions for Dr Chia

 

[halcyon]

@halcyon, I am not sure if the 3A protein is present in echovirus; but if it were, then itraconazole might be good for your echovirus infections as well.

Thanks Hip, I do already have this one on my list of things to try.

 

[Hip]

@Jesse2233 I just found a study showing that fluoxetine (Prozac) also inhibits CVB4, so that's another one against this virus. I understand though that the antiviral dose of fluoxetine is quite high compared to its usual antidepressant dose of 20 mg, so that may limit its viability.

In this particular study, the fluoxetine concentration of 5.48 μM used in the cell line would work out to a human oral dose of 94 mg, which is high compared to 20 mg.

 

[mrmichaelfreedmen]

I was using this dihydroquercetin (DHQ) product: Swanson Ultra Russian Rejuvenator | 60 Capsules - £14.35

I believe this form of DHQ is a molecular complex of dihydroquercetin and vitamin C (based on the Russian drug Ascovertin). I am not sure why they complex DHQ with C, but it may be to enhance DHQ absorption and bioavailability.

DHQ by the kilo: http://www.balinvest.lv/shop/

I understand from @halcyon that Dr Chia is now recommending DHQ for antiviral purposes. DHQ is a potent antiviral, as effective as ribavirin for coxsackievirus B4.

However, the problem with DHQ is that its oral absorption is only a measly 0.49% (see this study; note that DHQ is also called taxifolin). Though I read that oral DHQ absorption goes up to 36% if dissolved in lipid solution. So when I took my DHQ, I dissolved the powder in heated coconut oil first. I am hoping that will get me 36% absorption (though one would really need to explore which oils or lipids are best suited to promoting DHQ oral absorption).

From the CVB4 study, I worked out you would want a human injectable dose of around 500 mg DHQ daily; this is equivalent to the study's intraperitoneal dosing protocol for mice. Now if we assume 36% absorption in lipid solution (like coconut oil), that corresponds to a human oral dose of around 1400 mg of DHQ in lipid solution.

My problem with DHQ is that even at oral doses of just 180 mg, DHQ causes me a lot of brain overstimulation. This overstimulation I think is likely due to adenosine receptor antagonism: quercetin is an adenosine receptor antagonist, and I am guessing DHQ, which is related to quercetin, may be also. The stimulant caffeine works by adenosine receptor antagonism.

The brain overstimulation was too strong for me, so I stopped taking DHQ. I am trying to find a workaround for this, to prevent the adenosine receptor antagonism and the resultant overstimulation caused by DHQ.

@Hip what brand NAG do you use?

I used 6 per day of the Swansons brand DHQ on top
of the 600mg oxymatrine and 2gram inosine with no effect.

Amantadine at 25mg gave me headaches and nausea which made me quit. And Epivir had no effect what so ever.

With extremely high nagalase levels, I think the only thing that will correct my immune inbalance is GcMAF and time.

Cheney seems to think that artusenate being a redox shifter has a very wide antiviral range and is the next compound I might try.

 

[Hip]

@Hip what brand NAG do you use?

I used 6 per day of the Swansons brand DHQ on top
of the 600mg oxymatrine and 2gram inosine with no effect.

You are asking about N-acetyl-glucosamine? I use the Jarrow brand. Were you tested positive for an active infection with coxsackievirus B4, the virus that DHQ targets?