Rega Compound 17 & Compound A - Potential Cures for Chronic Coxsackie B

Sidny

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By the way, this source also describes the isolation of poliovirus in patients with post-polio syndrome, a syndrome indistinguishable from ME. So this study equally implies the persistence of both type B and type C enteroviruses. (Multiple caveats apply.)

Although the first reports on post-polio syndrome claimed that the symptoms of post-polio syndrome do not become apparent until 10-20 years after poliovirus infection, they really meant that the symptoms do not become apparent to doctors until 10-20 years after poliovirus infection. The medical community refused to recognize post-polio syndrome for decades.
Very interesting thanks for your insight on this @Pyrrhus

I find this information rather significant in the context of ME and like diseases especially If a subset of them are driven by enteroviruses. I think unfortunately, a bulk of the current ME researchers have neglected persistent enteroviral infections as a driver of this and other diseases.

If better more widespread tests were available for enteroviruses and something like this new Rega compound were implemented as a treatment, maybe it would be enough to halt or reverse the disease process before turning into severe ME that like you mentioned, sounds an awful lot like post-polio syndrome.
 

Hip

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Although the first reports on post-polio syndrome claimed that the symptoms of post-polio syndrome do not become apparent until 10-20 years after poliovirus infection, they really meant that the symptoms do not become apparent to doctors until 10-20 years after poliovirus infection.
I've not heard before that post-polio symptoms can become apparent immediately after acute polio infection; I only thought post-polio syndrome appeared many decades later, usually in old age when there is some weakening of the immune system.


I agree that when post-polio arises, it does look like a chronic infection with poliovirus.

Although to be sure that post-polio is indeed do to chronic non-cytolytic poliovirus infection (rather than a normal lytic infection), I think you would have to get hold of some infected brain tissue samples, and test the ratio between positive and negative stand poliovirus RNA. If the ratio is very low, close to 1, it demonstrates the presence of non-cytolytic infection

(In a normal lytic infection, there is a ratio of about 100 times more positive stand RNA than negative. But in non-cytolytic infection, that ratio goes down to a figure closer to 1. So a ratio of positive to negative strand RNA close to 1 a characteristic signature of non-cytolytic infection.)

In the case of ME/CFS, and also that other chronic coxsackievirus B disease dilated cardiomyopathy, it's been demonstrated the infection in the tissues has a positive to negative strand ratio close to 1, thus demonstrating the presence of non-cytolytic infection.
 

Pyrrhus

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I read somewhere in the last few days that the crater or pocket on the viral capsid which Rega Compound 17 locks into is crucially important in the lifecycle of the virus, and thus this is expected to prevent drug resistance mutations from arising, because any genetic variation of the pocket shape would likely cause the viral lifecycle to fail.
That’s the same “wishful thinking” we heard about the capsid pocket that pleconaril binds to. The last time I spoke with John Chia, he mentioned that Johann Neyts held 50% of the development rights for this Rega compound, which may explain why his paper seems a bit overenthusiastic about the prospects of compound 17. If the capsid pocket were really so critically conserved, then you might expect the drug to probably work for all CVB strains, not just some of them.

I have noted that, in the papers that I have read that found enterovirus in brain tissue, none of them found extracellular capsids. I wonder if, in the central nervous system, enteroviruses move from cell to cell primarily via extracellular vesicles that cross the synaptic cleft. These extracellular vesicles often contain mutated, nonfunctional capsids.

a bulk of the current ME researchers have neglected persistent enteroviral infections as a driver of this and other diseases.
Yeah, unfortunately there is a general prejudice against researching infectious causes for diseases. This goes back to circa 1973, when the U.S. CDC declared that, thanks to widespread public vaccination programs, the infectious disease problem had effectively been solved and that future research funding should instead focus on what they called “chronic disease” and the lifestyle factors that lead to “chronic disease”. It’s truly bizarre that this doctrine still dominates research funding today, almost 50 years later.

If better more widespread tests were available for enteroviruses and something like this new Rega compound were implemented as a treatment, maybe it would be enough to halt or reverse the disease process
That’s the hope. I have an easier time envisioning the development of an effective treatment than I do have envisioning the development of an effective diagnostic test. So, I wouldn’t be surprised if we had an effective treatment years before we have an effective diagnostic test!
 

Hip

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It’s truly bizarre that this doctrine still dominates research funding today, almost 50 years later.
Yes, I think it is high time governments realized the very real possibility that infectious pathogens are the hidden cause of a vast array of chronic diseases. Only when governments understand this will they set up major initiatives analogous to Nixon's war on cancer campaign. We need to declare war on pathogens, and develop better vaccines and better antivirals.
 

Hip

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I just sent the following short message to the Bill & Melinda Gates Foundation:
Kennedy set the goal of putting man on the moon. Nixon declared war on cancer. What's the next big project a visionary president or charitable foundation should undertake in order to move humanity forward?

The answer is to declare war against the everyday infectious pathogens that researchers in the know understand are the likely cause of most chronic diseases. See Prof Paul Ewald to understand why.

This is what the Gates Foundation needs to do. Not just poliovirus, but all pathogens.
 

Sidny

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I just sent the following short message to the Bill & Melinda Gates Foundation:
Short and sweet. Thanks for your continued efforts on this front. You’re one of the few raising awareness and taking action on the subject. Our best chance for change is to reach out to those that have the power to make a a difference.
 

Hip

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Short and sweet. Thanks for your continued efforts on this front. You’re one of the few raising awareness and taking action on the subject. Our best chance for change is to reach out to those that have the power to make a a difference.
Unfortunately it had to be short and sweet, as when I went to the Bill & Melinda Gates Foundation website, I found their contact page limited messages to 500 characters.
 

Pyrrhus

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I think you would have to get hold of some infected brain tissue samples, and test the ratio between positive and negative stand poliovirus RNA. If the ratio is very low, close to 1, it demonstrates the presence of non-cytolytic infection
Exactly. That would indeed be the best way to test if an infection has gotten stuck in the dsRNA intermediate state that defines the persistent phase of enteroviral infection.

Interestingly, enteroviruses are not the only viruses to get stuck in the dsRNA intermediate state. Flaviviruses can also get stuck in the dsRNA intermediate state. (I don't know if flaviviruses get 5' terminal deletions, but one of their capsid proteins doubles as a viroporin that raises the Ca2+ concentration.)

Yes, I think it is high time governments realized the very real possibility that infectious pathogens are the hidden cause of a vast array of chronic diseases.
If you like Paul Ewald, you might like the attached paper from Arthur Rheingold. Rheingold is a big name in the epidemiology community, as well as a PACE critic.
 

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Hip

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Interestingly, enteroviruses are not the only viruses to get stuck in the dsRNA intermediate state. Flaviviruses can also get stuck in the dsRNA intermediate state.
Yes, I've seen a few interesting articles about defective virus infections with dengue virus (a flavivirus).

I had a friend in Brazil who caught dengue there about 20 years ago, and he had poor health and fatigue forever after. A study indicated that dengue can cause a post-infectious fatigue syndrome. So this looks like another case of a defective, non-cytolytic virus hanging around in the body and causing a fatiguing illness.

Most interestingly, I came across this paper on defective EBV infections. I've never been able to find any further info on defective EBV, but I wonder whether in the case of EBV-associated ME/CFS, it is this defective EBV that causes the disease.
 
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