Enteroviruses - revisited

Chrisb

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@Hip

I was very interested to see the list of antivirals which you posted particularly as it contained both fluoxetine and amantadine. I thought that this story from my short, and unsuccessful, career as a guinea pig might interest you. Unfortunately much time has elapsed and, as you know, I am not too good on details. It my be seen as a cautionary tale.

In 1991 there seemed to be a theory that our form of ME was caused by the effects of a virus on serotonin and in particular certain receptors on serotonin cells. As I recall it these receptors were, supposedly, specifically targeted by a then new SSRI, sertraline or Lustral. (The cynic in me now wonders whether this was merely a solution looking for a problem.)

A treatment was devised using sertraline off label in conjunction with amantadine. Sertraline was taken for a period of, say, two weeks or a month to block the receptors and then amantadine was introduced at low and then increased dose as an antiviral. I was warned that I might feel worse for a time but that this should pass.

There seemed to be no effect of any sort until my next relapse which occurred pretty much as usual. Then instead of making my usual partial recovery in 2 and 1/2 days I continued in full worse than usual relapse mode for weeks, hardly able to get my head off the pillow. On thinking about this it did occur to me that there may have been something about the theory which was correct, but that instead of preventing the relapse it in fact interfered with the normal recovery process. Having been told to expect to get worse before I got better I continued taking the drugs for some time, which was a mistake, but in that state rational judgment is beyond one.

Unfortunately before I could have a sensible discussion with the consultant who prescribed this treatment, on the advice of a Professor elsewhere, the clinic was closed. These possible effects would never have made it back to the expert whose idea it was.

Of course it may all have been coincidence, but caveat emptor.
 

knackers323

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@Chrisb very intrresting. Was this a widely held theory, ive not really heard about it. The closest I've heard is the two drugs that worked on serotonin that were supposedly meant ti be helpful a few years back but it seemed to die out.

Do you know anymore about the theory? How it came about. Was it followed up on etc. Why amantadine was used as the antiviral?
 

Chrisb

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@knackers323

I think the idea came from Peter Behan with whom my consultant was in contact. I have little more information as it is all a long time ago and my memory of the time is very hazy. I think that he was doing a lot of work on serotonin at the time and I seem to remember having a tape of a lecture in which some aspects of this were discussed. I do not know whether there was any wider interest in the idea at the time.
 

eljefe19

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@Hip hip check this out dude. I don't know if you've come across this but I stumbled onto some very interesting research on the Pseudo Vitamin B, PABA.
https://en.m.wikipedia.org/wiki/4-Aminobenzoic_acid

According to research from 1999, and then subsequent research by the same Russian team, showed that PABA was an interferon alpha/beta inducer, and also displayed virucidal tendencies. PABA deficiencies exist when the right colonic bacteria to absorb it is missing. Possible benefits in IBS as well.

Check it out:
https://www.ncbi.nlm.nih.gov/m/pubmed/10483491/

http://link.springer.com/article/10.1023/A:1016871219882
 

Hip

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According to research from 1999, and then subsequent research by the same Russian team, showed that PABA was an interferon alpha/beta inducer, and also displayed virucidal tendencies.
Thanks for the link. There are quite a few supplements that induce interferon alpha and beta. See this post. Astragalus is included in Dr Chia's Equilibrant formulation.



@Hip look at what Luteoloside does to Enterovirus 71 by inhibiting 3c protease (potentially good for broad spectrum AV?):

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0148693
Thanks for the link, but it does not look that promising, for several reasons:

The study found that the selectivity index (SI) for luteoloside is just 5.3, which is not very high. The selectivity index is a measure of antiviral potency. To give you an example, this study found that the antiviral drug amantadine has an SI = 20.12 against echovirus 18, and ribavirin has an SI = 13.11 against the same virus. Sometimes you see SI values around 100 or 200 for some antiviral drugs.

A good antiviral study will usually calculate the selectivity index, or else will compare the potency of the antiviral compound being tested to well known antiviral drugs such as ribavirin. Sometimes the selectivity index is stated in the paper abstract; but sometimes the SI is buried in the full paper somewhere. (By the way, if you need to access the full paper for a study, it can usually be found on Sci Hub if you cannot find it elsewhere. )

Though because the selectivity index is determined in vitro in a cell line, depending on the cells used, you can get widely different values for SI. But that just means that the antiviral is better at fighting the virus in certain types of cell, but not so good in other types of cell.

The selectivity index (SI) is also known as the therapeutic index (TI), therapeutic window, therapeutic ratio, selection index, and the safety window.



The study also said that the antiviral effect of luteoloside was similar to the effect of rutin, and rutin you can easily buy as a supplement (I don't think luteoloside is available as a supplement). This study found rutin and fisetin have an SI of more than 10 for enterovirus 71.

But note that antivirals which work for enterovirus 71 likely will not work for coxsackievirus B or echovirus. Most antivirals are quite viral species specific in their effects; though you do also get some broad-spectrum antivirals.
 
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eljefe19

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Interesting . Why by chance did you recommend taking DMAE along with Inosine?

Also how did Cyclopheron work for you?
 

Hip

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Why by chance did you recommend taking DMAE along with Inosine?
Imunovir (inosine pranobex) is a molecular complex of inosine and dimethylaminoisopropanol (DMAIP). There was some ideas offered that DMAE could play the role of DMAIP.



Also how did Cyclopheron work for you?
I did not take it for long. Some of these Russian interferon-inducing immunomodulators don't work as well as is claimed. If I remember correctly, they may stop working after the first few days. Or in some cases, they induce interferon in animal studies, but not in humans.
 
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eljefe19

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I ordered some DMAE as I've been taking Inosine for about a month and a half now. Apparently I should take a month off at the end of 60 days taking it?

So the goal is to boost interferon alpha and beta but preferably not gamma? Gamma seems to be destructive. I'm going to try PABA but I'm thinking maybe Astragalus should be avoided? I take 2g of Astragalus at night, but actually should probably take a break anyways as it seems immunomodulators should be cycled right?? Do you think Oxymatrine should be cycled? I ramped up my dose on equilibrant up to 6 tabs and then subsequently took Oxymatrine individually at 800mg per night. Down to 400mg now as a maintenance dose.
 

halcyon

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So the goal is to boost interferon alpha and beta but preferably not gamma?
From my recent understanding, increasing interferon beta is probably not ideal in our situation. It's bizarre because interferon alpha and beta use the same receptor, but they have different physiological effects. Interferon beta has been associated with inducing viral persistence in animal models, and it also might decrease T cell activation and interferon gamma release, which I believe is the exact opposite of what we need/want in persistent enteroviral ME.
 

eljefe19

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From my recent understanding, increasing interferon beta is probably not ideal in our situation. It's bizarre because interferon alpha and beta use the same receptor, but they have different physiological effects. Interferon beta has been associated with inducing viral persistence in animal models, and it also might decrease T cell activation and interferon gamma release, which I believe is the exact opposite of what we need/want in persistent enteroviral ME.
Hmm, So something like PABA which boosts both alpha and beta would be of negligible use then?
 

Hip

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Do you think Oxymatrine should be cycled?
No, the opposite: if it is working for you, Dr Chia says you need to keep taking it, otherwise you will lose any gains made.

How long have you been taking oxymatrine? Did you notice any worsening of symptoms on it? Oxymatrine often makes patients feel worse before they feel better, and this is a good sign if you feel worse, especially symptoms like fever.
 

eljefe19

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No, the opposite: if it is working for you, Dr Chia says you need to keep taking it, otherwise you will lose any gains made.

How long have you been taking oxymatrine? Did you notice any worsening of symptoms on it? Oxymatrine often makes patients feel worse before they feel better, and this is a good sign if you feel worse, especially symptoms like fever.
I did feel worse initially after starting Equilibrant. Definite flu like symptoms. I was unsurprised by this and was able to push through up to 800mg Oxymatrine at night. I am about 50% improved since starting Oxymatrine, however I have not been very scientific about my supplementation. The recent improvement is not due solely to Oxymatrine however I do believe it has helped to lower viral loads. I no longer feel flu-ish, only fatigued.
 

Hip

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@eljefe19 This post and the ones following it give some info about the negative consequences of stopping oxymatrine too soon. For women, I believe you need to take it indefinitely, else the virus will return; for men, you can stop after some time (I would guess after around a couple of years).
 

eljefe19

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@eljefe19 This post and the ones following it give some info about the negative consequences of stopping oxymatrine too soon. For women, I believe you need to take it indefinitely, else the virus will return; for men, you can stop after some time (I would guess after around a couple of years).
Thx hip. There may not be as much info on this, but what about Astragalus? Inosine? Reishi? Is there any need to cycle these?

Also, what do you think about Andrographis? I remember you saying that it possibly could be synergistic with Oxymatrine, and also inhibits interferon gamma. However @halcyon was saying that interferon gamma may be beneficial in chronic enterovirus infection.