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Enteroviruses - revisted

Hip

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Is there a way to utilize 120 x 200mg capsules or at least information relating to those details?
If you are looking for enterovirus treatments, the ones that leading enterovirus ME/CFS researcher Dr John Chia uses are: oxymatrine, inosine, Epivir and tenofovir. He also sometimes uses interferon beta in severe patients.

We are also expecting two potent new anti-enterovirus drugs to appear in a matter of a few years: these are code named Rega Compound A and Rega Compound 17.
 
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If you are looking for enterovirus treatments, the ones that leading enterovirus ME/CFS researcher Dr John Chia uses are: oxymatrine, inosine, Epivir and tenofovir. He also sometimes uses interferon beta in severe patients.

We are also expecting two potent new anti-enterovirus drugs to appear in a matter of a few years: these are code named Rega Compound A and Rega Compound 17.
Apologies @Hip my brain fog is at play currently which has me missing words. I meant to say, is there a way to utilize 120 x 200mg Ribavirin capsules with out the dreaded side effects previously mentioned.....or at least point me to the information that would allow me to understand appropriate Ribavirin dosing.

I should have invested in the INF suppositories instead 😊
 

Hip

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Apologies @Hip my brain fog is at play currently which has me missing words. I meant to say, is there a way to utilize 120 x 200mg Ribavirin capsules with out the dreaded side effects previously mentioned.....or at least point me to the information that would allow me to understand appropriate Ribavirin dosing.

I should have invested in the INF suppositories instead 😊
Dr Chia's own experiments with ribavirin for enterovirus ME/CFS did not produce useful results. Some improved while on the drug, but nearly all went back to baseline at the end of the treatment period. There are reasons why you cannot use ribavirin indefinitely (due to toxicity), so unfortunately ribavirin does not seem to lead to long-term improvement.

Here's a quote from Dr Chia's paper on ribavirin and interferon:
Seven patients had marked improvement of fatigue and other flu-like symptoms within 2 to 3 weeks of taking ribavirin. Mild headaches and nausea were the most common side effects.

Three patients had an 11% to 15% reduction of hemoglobin at the end of the second month, but were able to continue the medication without dose modification.

Three of the 7 patients (B, C, and D) started to deteriorate before the end of the 4-month treatment period, although all 3 were still better than baseline when the treatment was completed. Six patients relapsed with recurrence of all of the symptoms of CFS within 1 to 2 weeks of drug discontinuation.

All seven patients had a fourfold or greater reduction of neutralizing antibody during treatment. However, the levels rebounded at the end of treatment in 3 patients (B, C, and D), who deteriorated before the end of treatment, and in all other four responders after the treatment was completed (Figure 1).

You might like to explore the enterovirus treatments Dr Chia uses here.
 

Pyrrhus

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is there a way to utilize 120 x 200mg Ribavirin capsules with out the dreaded side effects previously mentioned
Unfortunately not. The maximum safe dosage for Ribavirin is about 800-1200mg per day. The minimum effective dosage for enteroviruses is about 2200mg per day. (assuming a 60kg adult male and four divided doses 6-8 hours apart)

Therefore, the minimum effective dosage is roughly double the maximum safe dosage. That's a negative therapeutic window.

The literature contains a number of pilot trials that each suggest that the toxicity of Ribavirin could be lessened if you only add vitamin C, vitamin E, acetyl-L-carnitine, and/or alpha-lipoic acid. None of these pilot studies panned out.

Hope this helps.
 
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Unfortunately not. The maximum safe dosage for Ribavirin is about 800-1200mg per day. The minimum effective dosage for enteroviruses is about 2200mg per day. (assuming a 60kg adult male and four divided doses 6-8 hours apart)

Therefore, the minimum effective dosage is roughly double the maximum safe dosage. That's a negative therapeutic window.

The literature contains a number of pilot trials that each suggest that the toxicity of Ribavirin could be lessened if you only add vitamin C, vitamin E, acetyl-L-carnitine, and/or alpha-lipoic acid. None of these pilot studies panned out.

Hope this helps.
I now see what you mean. I tried Tamiflu for 5 days with out much change in symptoms. Will invest in some INF suppositories from russia and will report back.
 
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@Hip would Vorconazole have the same anti-enterovirus effects as Itraconazole ?

itraconazole (anti-fungal) broad-spectrum antiviral for enteroviruses including CVB3, CVA16, poliovirus, enterovirus-71, enterovirus 68, rhinovirus 1 2
 

Hip

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@Hip would Vorconazole have the same anti-enterovirus effects as Itraconazole ?

itraconazole (anti-fungal) broad-spectrum antiviral for enteroviruses including CVB3, CVA16, poliovirus, enterovirus-71, enterovirus 68, rhinovirus 1 2
I don't know, but sadly I found out that most of the antiviral supplements and off-label drugs in my list will not have any significant antiviral effect in vivo, when you actually take the supplement or drug. That includes itraconazole. It's not going to work. (I also tried itraconazole for several months, and found no benefits).

Using pharmacokinetic data, I spent a lot of time calculating how effective each of these substances in my list is when taken orally. From my pharmacokinetic calculations, it turns out that most of these substances, although they may be potently antiviral in vitro, have no significant antiviral in vivo when you actually take it. This is because the concentrations of the substance used in the in vitro tests are much higher than the blood concentrations that can be achieved in vivo.

It's mostly only the commercial pharmaceutical antivirals like interferon in my list that actually have an powerful antiviral effect in vivo.

To put it into perspective: in my pharmacokinetic calculations, I was able to calculate what I called the Potency Factor for each antiviral in my list, which represents the antiviral power of the substance in vivo, when it is taken orally.

So I calculated the Potency Factor of pleconaril to be around 5000 (pleconaril is a pharmaceutical anti-enterovirus drug that was unfortunately never bought to market). Several thousand is the typically sort of Potency Factor that many commercial pharmaceutical antivirals have (this is what I found in my calculations).

Whereas when I calculated the Potency Factor of itraconazole, that turned out to be only around 30. So itraconazole's antiviral effects for enterovirus are negligible in vivo. And unfortunately most substances in my list turned out to have similarly low Potency Factors.
 
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Understood @Hip and it makes sense. Would Arbidol be the same?

Have tried Valsartan 160mg every day for a full 12 months and found no symptom improvement. And as above (Tamiflu for 5 days) same outcome.

We should probably stick with the compounds Dr Chia has found somewhat useful. Will be trying the INF suppositories soon and may combine them with some Arbidol have purchased.

I can only research this from work as not in a financial position to have internet access at home. But will report back and maybe start a new thread documenting my INF suppositories journey.
 

Hip

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Understood @Hip and it makes sense. Would Arbidol be the same?
For Arbidol (umifenovir) I was not able to calculate the Potency Factor, for a number of reasons (one of which is that Arbidol may have immunomodulatory effects as well as antiviral actions in fighting viruses, and accounting for the former is beyond the scope of my calculations; I can only calculate the antiviral action).

Arbidol might be useful for coxsackievirus B ME/CFS, as there are a couple of in vivo mouse studies that showed this drug has a substantial antiviral effects against acute CVB infection:
Arbidol CVB4 in vivo study: 100, 200, and 300 mg/kg of Arbidol dose-dependently inhibited the viral load in myocardial tissues in mice, and reduced CVB4-induced IL-10 increase.

100 mg/kg in mice corresponds to a human dose of 100 / 12.3 = 8.1 mg/kg (since 12.3 is the mouse-to-human conversion factor). Thus for an 80 kg human, this is an equivalent oral dose of 648 mg of Arbidol.
Arbidol CVB5 in vivo study: 25 and 50 mg/kg of Arbidol were given to mice infected with CVB5. The heart and lungs showed sign of infection. Results:
Untreated control group of mice: all died.
25 mg/kg of Arbidol group of mice: half survived.
50 mg/kg of Arbidol group of mice: all survived.

50 mg/kg in mice corresponds to a human dose of 50 / 12.3 = 4.1 mg/kg, which for an 80 kg human is an equivalent oral dose of 328 mg of Arbidol.

But as you can see from these studies, the equivalent human dose is quite high, around 300 to 600 mg. It would be a little bit expensive to take 600 mg of Arbidol daily. I actually tried taking 100 mg daily for around 5 weeks, but did not notice any improvements in ME/CFS symptoms (I have an active CVB4 infection). But this was a low dose.

@Steve4Andrea's wife who has ME/CFS tried Arbidol 400 mg daily (see this post), and observed some improvements. I am not sure of the long-term outcome, as he stopped posting.

Arbidol is a well-tolerated drug, and I have seen studies where doses of 800 mg daily were used.

So it might be worth trying Arbidol as an experiment. At rupharma.com, Arbidol costs 1 euro for each 100 mg tablet. Arbidol can also be bought here, here, here and here.
 
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For Arbidol (umifenovir) I was not able to calculate the Potency Factor, for a number of reasons (one of which is that Arbidol may have immunomodulatory effects as well as antiviral actions in fighting viruses, and accounting for the former is beyond the scope of my calculations; I can only calculate the antiviral action).

Arbidol might be useful for coxsackievirus B ME/CFS, as there are a couple of in vivo mouse studies that showed this drug has a substantial antiviral effects against acute CVB infection:





But as you can see from these studies, the equivalent human dose is quite high, around 300 to 600 mg. It would be a little bit expensive to take 600 mg of Arbidol daily. I actually tried taking 100 mg daily for around 5 weeks, but did not notice any improvements in ME/CFS symptoms (I have an active CVB4 infection). But this was a low dose.

@Steve4Andrea's wife who has ME/CFS tried Arbidol 400 mg daily (see this post), and observed some improvements. I am not sure of the long-term outcome, as he stopped posting.

Arbidol is a well-tolerated drug, and I have seen studies where doses of 800 mg daily were used.

So it might be worth trying Arbidol as an experiment. At rupharma.com, Arbidol costs 1 euro for each 100 mg tablet. Arbidol can also be bought here, here, here and here.
Thanks @Hip Do you think one stat dose on an empty stomach once per day(morning) at 300 - 600mg each would be sufficient?
 

Hip

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Will be combined with 3 million IU INF suppositories.
You might consider starting slowly with the interferon suppositories, as interferon at full doses can worsen symptoms, making you more tired, and it can also cause depression. Dr Chia's dosing for subcutaneous interferon is 3 million IU three times weekly (for 2 months or more), and he would often find that ME/CFS patients found it hard to handle the worsening of symptoms caused by interferon .
 
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You might consider starting slowly with the interferon suppositories, as interferon at full doses can worsen symptoms, making you more tired, and it can also cause depression. Dr Chia's dosing for subcutaneous interferon is 3 million IU three times weekly (for 2 months or more), and he would often find that ME/CFS patients found it hard to handle the worsening of symptoms caused by interferon .
I haven't been able to find documentation detailing the INF plasma levels with the suppositories. I'd imagine the route of application would be much less potent Vs SubQ.
 

Hip

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I haven't been able to find documentation detailing the INF plasma levels with the suppositories. I'd imagine the route of application would be much less potent Vs SubQ.
Yes, this paper says the bioavailability of interferon suppositories is much lower than subcutaneous interferon; but nevertheless you may want to be on the lookout for symptoms like increased depression or fatigue when you are trying the suppositories.

I was experimenting with taking 3,000 IU of the interferon suppository intranasally, because I was thinking this might get the interferon into the brain better. The suppositories are soft and easily cut. Then they can be melted, sucked up into a pipette, and inserted as a liquid into the nasal cavity.
 

Hip

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The nasal spray is interesting as well as the injections...probably more so.
The Russian interferon alfa injections are incredibly cheap compared to Western interferon alfa. When Dr Chia gives ME/CFS patients 3M IU of interferon alfa three times a week, he says the monthly cost is around $6000. So that's about $500 for one injectable 3M IU dose.

Yet Cherry pharmacy sell a 5M IU injectable dose for about $10 !


In any case, whether using Western or Russian interferon injections, after some time (many months), the body usually starts to make antibodies which target and disable the injected interferon, so it will stop working.

But if you use the suppository route of administration (and I expect the intranasal too), you do not get this antibody issue.

So if you are trying interferon injections, you may want to take that for a limited time (eg, 2 or 3 months), in order to try to avoid the creation of antibodies; and then if there are any benefits for your ME/CFS, you could switch to interferon suppositories/intranasal using maintenance doses.


I actually wrote to Dr Chia to explain this strategy that I thought of (though I am not sure if he understood the idea behind it). For enterovirus ME/CFS patients, Dr Chia found interferon injections very effective, allowing over 50% of bedbound ME/CFS patients to return to work after treatment. But these patients tended to relapse after around 4 months to a year (the relapse was often triggered by a bout of heavy exertion), most likely because the virus was not fully eliminated by the interferon, and so eventually returned.

So my idea is to take the normal 2 or 3 month course of injectable interferon that Dr Chia uses, and once patients have greatly improved, to switch to taking low doses of interferon suppositories for maintenance.

The idea is that once in remission, if you continue to take low doses of interferon as a suppository indefinitely, that may prevent the virus from returning. But most importantly, the suppository administration would allow long-term low-dose interferon use without the antibody issue occurring.


Dr Chia now uses interferon beta for enterovirus ME/CFS, but I have not seen any cheap interferon beta available.
 
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The Russian interferon alfa injections are incredibly cheap compared to Western interferon alfa. When Dr Chia gives ME/CFS patients 3M IU of interferon alfa three times a week, he says the monthly cost is around $6000. So that's about $500 for one injectable 3M IU dose.

Yet Cherry pharmacy sell a 5M IU injectable dose for about $10 !


In any case, whether using Western or Russian interferon injections, after some time (many months), the body usually starts to make antibodies which target and disable the injected interferon, so it will stop working.

But if you use the suppository route of administration (and I expect the intranasal too), you do not get this antibody issue.

So if you are trying interferon injections, you may want to take that for a limited time (eg, 2 or 3 months), in order to try to avoid the creation of antibodies; and then if there are any benefits for your ME/CFS, you could switch to interferon suppositories/intranasal using maintenance doses.


I actually wrote to Dr Chia to explain this strategy that I thought of (though I am not sure if he understood the idea behind it). For enterovirus ME/CFS patients, Dr Chia found interferon injections very effective, allowing over 50% of bedbound ME/CFS patients to return to work after treatment. But these patients tended to relapse after around 4 months to a year (the relapse was often triggered by a bout of heavy exertion), most likely because the virus was not fully eliminated by the interferon, and so eventually returned.

So my idea is to take the normal 2 or 3 month course of injectable interferon that Dr Chia uses, and once patients have greatly improved, to switch to taking low doses of interferon suppositories for maintenance.

The idea is that once in remission, if you continue to take low doses of interferon as a suppository indefinitely, that may prevent the virus from returning. But most importantly, the suppository administration would allow long-term low-dose interferon use without the antibody issue occurring.


Dr Chia now uses interferon beta for enterovirus ME/CFS, but I have not seen any cheap interferon beta available.
That is indeed a vast price difference. And yes that application sounds feasible long term. I believe that INF activates the intracellular immune system and therefore repairs the Th1 deficiency long enough to eradicate the EV infection, however after INF supplementation comes to an end the Th1 deficiency reoccurs along with reinfection. Chia does however speak of enterovirus "seeds" which may play part of the reinfection puzzle.