The Enterovirus Theory of Disease Etiology in ME/CFS: A Critical Review (O'Neal and Hanson, 2021)

[Pyrrhus]

Re: Molnupiravir

Here are the published results from the Phase I trial, which reported that low doses of the drug were well tolerated:
https://journals.asm.org/doi/full/10.1128/AAC.02428-20

The question in my mind is whether the doses and dosing frequency in the trial were high enough to be effective against the coronavirus. I don't know if molnupiravir has yet been tested against any enteroviruses.

The final results from the Phase 3 study are now available and are somewhat disappointing. Molnupiravir reduced the risk of hospitalization and death among high-risk Covid patients by 30 percent, down from an earlier estimate of 50 percent. Some have said that it might be due to the low dosing frequency:
https://www.merck.com/news/merck-an...t-risk-adults-with-mild-to-moderate-covid-19/

Does anyone know whether the antiviral made by Pfizer (Paxlovid) for Covid infection may have efficacy against enteroviruses?

Paxlovid is a coronavirus protease inhibitor, and protease inhibitors are generally only effective against the specific virus they were designed to inhibit. So paxlovid would generally not be expected to work on other types of viruses. (although there are sometimes exceptions.)

 

[Nuno]

Based on last Chia presentation on IACFSME 2021, he mentioned that the target we should be looking for is RdRp inhibitors. He also mentioned on a later podcast with Amy Proal having quite interesting results on people with Fibromyalgia and ME/CFS. that had Remdesivir administrated because of SarsCov2 infection.

I also know some people with MECFS who had positive results with Ribavirin and Favipiravir, though their toxicity doesn't allow continued use, also their potency is not very strong.


Where does that leaves us?

So there must be, out there, possible stronger and safer RdRp inhibitors, right?

 

[Pyrrhus]

Evolutionary Genetics of Human Enterovirus 71: Origin, Population Dynamics, Natural Selection, and Seasonal Periodicity of the VP1 Gene (Tee et al., 2010)
https://forums.phoenixrising.me/thr...ed-by-another-coronavirus.86397/#post-2380702
https://forums.phoenixrising.me/thr...ed-by-another-coronavirus.86397/#post-2385878

A similar genetic dating was performed for the virus Enterovirus A71, which concluded that this virus first emerged around 1940:

Evolutionary Genetics of Human Enterovirus 71: Origin, Population Dynamics, Natural Selection, and Seasonal Periodicity of the VP1 Gene (Tee et al., 2010)
https://journals.asm.org/doi/epub/10.1128/JVI.01019-09

Interestingly, this emergence of Enterovirus A71 at some point in the years around 1941 corresponds to the first recorded outbreaks of ME. Therefore, it has been suggested that the early outbreaks of ME might have been due to the emergence of this new virus Enterovirus A71. As time passed, this virus might have started to show up as isolated cases instead of as discrete outbreaks...

Wow. I just took another look at that paper. Apparently, a new strain of Enterovirus A71 appeared in 1984, the same time as the Incline Village/Lake Tahoe outbreak of ME/CFS! And a major outbreak of this new strain also occurred in 1997, the year that many others I know first fell ill.

 

[msf]

As I rewatched the webinar “Advances in our understanding of MECFS and the effects long COVID”, I found Maureen Hanson’s presentation about changes in the microbiome very interesting. She mentions that other disease states such as inflammatory bowel disease, HIV infection, non alcoholic fatty liver disease and Parkinson’s disease can lead to similar microbiome dysbiosis. What if the potential trigger for most of these diseases is a chronic latent infection of the gastrointestinal tract. Perhaps the viral trigger is not always a species of enterovirus but the end result is the same.

I think the importance of interactions/cross talk between the gut, brain, and immune system will make themselves evident as researchers continue their efforts to understand complex biologic systems. A first step might be to obtain tissue samples from the stomach and colon of MECFS patients. However, I suspect someone may need to develop a new technology to study complex interactions between the gut microbiome, immune system and the brain.

This is the hypothesis that KDM (and possibly Maes) have pursued for about 11 years now. Definitely seemed to be a fruitful one in my case. Hopefully Hanson and the other US researchers will be able to prove it beyond a reasonable doubt.

 

[sometexan84]

Evolutionary Genetics of Human Enterovirus 71: Origin, Population Dynamics, Natural Selection, and Seasonal Periodicity of the VP1 Gene (Tee et al., 2010)
https://forums.phoenixrising.me/thr...ed-by-another-coronavirus.86397/#post-2380702
https://forums.phoenixrising.me/thr...ed-by-another-coronavirus.86397/#post-2385878

I think EV 71 might eventually prove to be important, and very relevant to many of us...

just saying

 

[Pyrrhus]

Interesting comments from other threads:

On the possibility of performing a brain biopsy:

It's likely not common, but it's actually not rare either (Gelfand et al., 2015). There's a published case of an individual that developed rapidly progressing dementia. Not one, but two spinal fluid evaluations showed no infectious agents. A biopsy was taken from the temporal lobe and oops, what do you know, it tested positive for enteroviral RNA (Valcour et al., 2008). Once is bad luck, but oops, two more cases, same exact thing, spinal fluid negative, brain biopsy positive for enterovirus (Palacios et al., 2015; Garzo-Caldas et al., 2017). The latter two are more terrifying due to a) being fatal, and b) being caused by rituximab induced immune suppression.

And on the possibility of enteroviral persistence in the testicles:

I believe that enterovirus infects and persists in the testes also. It's rarely mentioned, but orchitis is noted as a symptom in Ramsay and Dowsett's patient cohort (13% of cases), as well as in the cohort from the 1965 Galveston, Texas outbreak (15% of cases), an outbreak that was theorized to be due to an enterovirus, despite not being able to isolate the pathogen. I personally seem to have some intermittent or low-grade symptoms that could be consistent with orchitis.

 

[Wishful]

The biopsy problem shows the limitations of taking samples: some processes produce localized abnormalities. Spinal fluid is easier to sample than taking samples from inside the brain, but shouldn't be taken as proof that there are no abnormalities in the brain fluid. I think this is part of why researchers haven't found the core dysfunction of ME yet: it resides in a place difficult to sample. Funding goes to the 'searching under the streetlight' projects instead.

 

[Nuno]

If these viruses reside in hard to reach places, would the antivirals be able to reach there? Since the immune system isn’t

And what about interferon? Since it’s part of immune system reaction, would it be able to reach there? @Pyrrhus

 

[godlovesatrier]

Reaching it as I understand is the tricky thing with entereoviral infections, purely because of the tissues it hides in and where it camps out. Be nice if we got more clarity around this in the coming years, possible that most of those patients of dr lerner may have also had entereoviral infections as I do not believe he tested for any of those.

 

[sometexan84]

Reaching it as I understand is the tricky thing with entereoviral infections, purely because of the tissues it hides in and where it camps out. Be nice if we got more clarity around this in the coming years, possible that most of those patients of dr lerner may have also had entereoviral infections as I do not believe he tested for any of those.

Precisely. The epithelial barriers in the body. This is why the Type III Interferons (Lambda) will theoretically work, where Type I IFN was never able to completely rid the body of the virus.

Type III works at the epithelial barrier, where most cells have the IFNLR-1 receptor (and lack Type I IFN receptors)

 

[godlovesatrier]

Can't wait to see what all your pathology reports look like. Will someone be collating all the data from peoples lab tests and what not so we can see how different people are doing over time?

 

[Thebirdman333]

what is the best test for enterovirus? And is there a lab somewhere in europe that does it?

Is there anyway to try IFN Lambda now?

Yes you can get it now see @sometexan84 thread about it but you have to let us know soon.

 

[mrmichaelfreedmen]

Thanks for bringing that up.

I'm not as informed about IFN-lambda/IL-28 as I would like to be, but trials with type I interferons generally showed promise only when combined with a direct-acting antiviral drug (DAA). These trials also demonstrated that including type I interferons in such a combination led to intolerable side effects, including brain inflammation. (The same might also be true for high doses of drugs that stimulate the intracellular interferon pathway, such as Ampligen or nitazoxanide.)

The ideal treatment would only consist of one or more DAAs that directly target the virus, without any inflammatory side effects.

Hope this helps.

nitazoxanide stimulates INF production for a very limited time frame - 14 days or so

 

[acer2000]

Based on last Chia presentation on IACFSME 2021, he mentioned that the target we should be looking for is RdRp inhibitors. He also mentioned on a later podcast with Amy Proal having quite interesting results on people with Fibromyalgia and ME/CFS. that had Remdesivir administrated because of SarsCov2 infection.

This is interesting...

Case report: Clearance of longstanding, immune-deficiency-associated, vaccine-derived polio virus infection following remdesivir therapy for chronic SARS-CoV-2 infection

https://pubmed.ncbi.nlm.nih.gov/36936936/

 

[forestglip]

According to one model of infected nerve cells, the dsRNA state will immediately separate into two ssRNA strands whenever the infected nerve cell activates. Thus, any neurological activity caused by physical or mental exertion will cause the dsRNA to separate, triggering renewed viral replication. If someone is taking a direct-acting antiviral drug (DAA) while physically or mentally exerting their self, then the drug has an opportunity to act on the virus, ideally preventing re-formation of the dsRNA state. This model remains theoretical pending experimental validation.

Do you have any links to further discussion or research about this theory?