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NZ team reactivate research into DRACO (renamed VTose), the universal antiviral that could cure ME/CFS

Hip

Senior Member
Messages
17,824
Here's the best apoptosis summary I have. I

Thanks for posting that EBV apoptosis pathway. (A nice simple diagram!)



I'm pretty sure EBV blocks at TRIF, Nf-KB+, RIP

As I mentioned above, the study says DRACO triggers apoptosis by targeting pathway steps such as Apaf-1 or FADD. I can't see Apaf-1 on the diagram, but FADD is there (at about 11 o'clock), and has an apoptosis pathway that does not appear to involve any of the EBV blocking points that you mention.

Though I have no confidence in my abilities to decipher such a complex apoptosis pathway, which I know absolutely nothing about.



The study does say that:
Pan-caspase and caspase-9 inhibitors eliminated DRACO-mediated apoptosis in the presence of dsRNA.

So presumably if EBV were able to inhibit caspase-9 or pan-caspase, then it would block DRACO.



I know that DRACO and VTose have not been tested against EBV, but there are plans to do so.
 

gbells

Improved ME from 2 to 6
Messages
1,491
Location
Alexandria, VA USA
One issue with EBV that seems to be true is it's almost impossible to eradicate if your having an immune issue or disease. So maybe not surprising if Draco struggled with it in practice, but who knows. I know valtrex and valcyte are meant to eradicate at high doses over 2 or 3 years, but it's a powerful herx off that stuff, not sure how anyone could do that without taking 6 months off work to weather the herx.

People once thought it was impossible to fly too. Luckily the Wright brothers came along.

Apoptosis is how the body normally eliminates viruses. Don't give up so easily.
 

gbells

Improved ME from 2 to 6
Messages
1,491
Location
Alexandria, VA USA
Thanks for posting that EBV apoptosis pathway. (A nice simple diagram!)





As I mentioned above, the study says DRACO triggers apoptosis by targeting pathway steps such as Apaf-1 or FADD. I can't see Apaf-1 on the diagram, but FADD is there (at about 11 o'clock), and has an apoptosis pathway that does not appear to involve any of the EBV blocking points that you mention.

Though I have no confidence in my abilities to decipher such a complex apoptosis pathway, which I know absolutely nothing about.



The study does say that:


So presumably if EBV were able to inhibit caspase-9 or pan-caspase, then it would block DRACO.



I know that DRACO and VTose have not been tested against EBV, but there are plans to do so.



The block is at FADD which prevents assembly of the DISC protein (RIP) that triggers necroptosis. As long as someone doesn't have EBV it will work but EBV completely blocks it. The chart is good but it doesn't go into this pathway on the diagram for whatever reason.

I think shocking the cell will bypass it. It definitely ramps up my periostitis clearance in the toes.

Good articles on the pathway:
https://ghr.nlm.nih.gov/gene/FADD
https://pubmed.ncbi.nlm.nih.gov/30136234/
 
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jstefl

Senior Member
Messages
250
Location
Brookfield, Wisconsin
@godlovesatrier
One issue with EBV that seems to be true is it's almost impossible to eradicate if your having an immune issue or disease. So maybe not surprising if Draco struggled with it in practice, but who knows. I know valtrex and valcyte are meant to eradicate at high doses over 2 or 3 years, but it's a powerful herx off that stuff, not sure how anyone could do that without taking 6 months off work to weather the herx.


Not everybody has a bad experience with Valcyte. I took Valcyte for 10 months back in 2009 and had no herx reaction at all. My only regret is that I wasn't able to continue taking it. Later I tried Valtrex and wasn't able to handle it.
 

godlovesatrier

Senior Member
Messages
2,545
Location
United Kingdom
I can't afford the valcyte sadly, it's just far too expensive. But I've heard mixed things more about valcyte than valtrex. Also without access to good blood tests I am more wary of experimenting with valcyte, due to potential for liver damage.

I took valtrex for about 5 days last month, but the headaches, nausea and washing machine feeling were very strong and that was from 500mg once a day. I'm going to attempt to titrate up from 250mg, see if I can get round it that way.
 

Hip

Senior Member
Messages
17,824
It may be of interest that one member of the longecity.org forum (named "soulprogrammer") is looking at getting some DRACO custom synthesized for his own personal use, mainly in his case as a protective treatment for coronavirus.

Has has been working with a professional virologist, in order to understand the DRACO paper and patent, and had a quote from a manufacturer, who said they could make and deliver the DRACO protein in 6 weeks. He is trying to raise interest for a group buy of the DRACO, so the cost can be shared between several people. See this thread.

Kimer Med have also posted some comments on that thread.
 

gbells

Improved ME from 2 to 6
Messages
1,491
Location
Alexandria, VA USA
Rider published one paper on DRACO. He confirms it works through FLICE to create DISC (RIP) to trigger necroptosis. However, we don't have any evidence that it would work in the presents EBV which prevents the DISC from forming.

FLICE info: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC99990/

The second natural process used by our approach is one of the last steps in the apoptosis pathway [14], in which complexes containing intracellular apoptosis signaling molecules, such as apoptotic protease activating factor 1 (Apaf-1) [15][16] or FLICE-activated death domain (FADD) [17][18], simultaneously bind multiple procaspases. The procaspases transactivate via cleavage, activate additional caspases in the cascade, and cleave a variety of cellular proteins [14], thereby killing the cell.

Here are the viruses that DRACO successfuly killed through necroptosis in vitro. EBV isn't listed telling me that it probably wasn't effective due to the above reason.
https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0022572.t001

Pharma companies won't fund it and the project is currently dead.

https://www.businessinsider.com/tod...ng-broad-spectrum-antiviral-2015-12?r=US&IR=T

It is nice to have a cure for the common cold but nobody is going to invest millions to cure a three day infection.
 

Hip

Senior Member
Messages
17,824
He confirms it works through FLICE to create DISC (RIP) to trigger necroptosis.

If you look at the DRACO patent, the word "apoptosis" appears 249 times. If I understand it correctly, the patent describes many different apoptosis mechanisms that can be used with DRACO.
 

gbells

Improved ME from 2 to 6
Messages
1,491
Location
Alexandria, VA USA
If you look at the DRACO patent, the word "apoptosis" appears 249 times. If I understand it correctly, the patent describes many different apoptosis mechanisms that can be used with DRACO.

From the patent fig 6 it looks like he's using a chimeric protein to mimic caspase, APAF-1 and FADD. It still has to form the DISC complex. Since EBV blocks the latent membrane protein 1 (LMP1) of EBV to prevent RIPK1 and RIPK3, modulates their ubiquitination status, and inhibits TNF, Smac mimetic and caspase inhibitor-induced necroptosis, you can't get the final necroptosis signal because of blocked DISC complex formation. I suspect his testing in EBV failed and this is why he didn't include it in the listed of viruses he successfully cured. He should have listed EBV as having failed in his PLOS1 publication.

I emailed Rider to ask him if he ever tested DRACO on EBV. I also asked him if he thinks it might work on the other ME viruses.
 
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Hip

Senior Member
Messages
17,824
I emailed Rider to ask him if he ever tested DRACO on EBV. I also asked him if he thinks it might work on the other ME viruses.

I've heard Rider rarely replies to any communication. Even Dr Chia tried to contact Rider, but got no response. You could however post a question on the longecity.org forum, where Kimer Med are currently answering questions on the DRACO threads.
 

gbells

Improved ME from 2 to 6
Messages
1,491
Location
Alexandria, VA USA
It's a paid forum and I prefer not to join. Feel free to post for me and report back any reply here at PR.

Since he filed the patent he'd better figure out a way to get the research on track. He only has 20 years to profit once a patent is filed. It could still be a useful medicine against several viruses-even the common cold.
 
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gbells

Improved ME from 2 to 6
Messages
1,491
Location
Alexandria, VA USA
It's a completely free forum.

@Hip Now if you try to register they demand you pay. So they must have recently changed it.
https://www.longecity.org/forum/index.php?app=core&module=global&section=register

Here's what I emailed him. Just copy it over and post it there then let us know if he replies.


Hello Todd. A number of us on the Myalgic Encephalomyetis forum Phoenix Rising are discussing DRACO's potential to help with ME. What we see with the condition is that it is caused by multiple coinfections of apoptosis inhibing viruses including (HHV6, EBV, CMV, varicella zoster, and non-cytolytic coxsackie enterovirus). The prevalence of EBV is high, 80% in ME patients posing a problem with using for EBV infected patients because EBV blocks the assembly of the DISC protein needed to trigger the signal for necroptosis. After reviewing your PLOS1 paper on the subject it seems you may have tested it on EBV but it didn't work. Did you ever try DRACO on EBV infected cells? Do you think DRACO would work for any of the over viruses listed above? Thank you in advance.
 
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Messages
17
The Kimer Med team have created a derivative of DRACO, which they named VTose, and they have already successfully tested VTose on 15 different viruses, and are planning to test it on the SARS-CoV-2 coronavirus.

Thanks, @Hip for the introduction.

Just a small correction here. Dr Rider is the one who tested and had success with 15 viruses. We are just getting started with VTose. We do plan to test against SARS-CoV-2, though, as you said.
 

gbells

Improved ME from 2 to 6
Messages
1,491
Location
Alexandria, VA USA
Hello Kimer, good to see you on the forum. I'm a former DC (also CNIM with training in clinical data management) disabled with ME but at a high level of functioning (at 11 years!). I do a lot of self expermentation and literature searching concerning how to trigger apoptosis in multiple chronic viral infections so I found VTose interesting. I have varicella zoster, EBV, HHV6 and coxsackie viral infections confirmed by Ig lab testing that I have been working on. I have a blog series with a lot of photos of periostitis clearing as treatment progresses. We could probably combine approaches to get past the EBV checkpoint block problem if you want to partner up. I think there could be a huge potential market for preventing cancer by treating EBV, also depression by treating HHV6 which causes depression through SITH1. I will message you.
 
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Messages
17
We could probably combine approaches to get past the EBV checkpoint block problem if you want to partner up. ... Message me or provide your contact information if you'd like to discuss.

Sure, happy to discuss.

gbells said:
So far I've learned that there are 2 versions of DRACO, one that uses Apaf to trigger Bip and another that uses FADD to trigger DISC both would be ineffective against EBV.

"DRACO" is actually a family of compounds. Rider tested against 7 different DRACOs in the PLoS ONE paper, and described several more in his patent. The compounds are chimeric, with a dsRNA detection domain, and an apoptosis induction, or "effector" domain. Both domains are typically only pieces of other proteins, which means they also have somewhat different biochemical characteristics than the full versions, including how they can be blocked.

Capture.JPG


I cross-posted my response to your earlier questions about EBV here:

https://forum.kimermed.co.nz/index.php?/topic/14-will-draco-be-effective-against-ebv/

For the reasons I explain there, as well as the chimeric aspect above, I'm optimistic that we can make VTose work against all Herpesviruses, including EBV. However, the only way to know for sure is to do the testing -- which we're planning to do.