Any reason to be hopeful that Pritelivir will do more for CFS than Valtrex?

[Forummember9922]

Considering the herpesvirus+CFS research of recent years,

https://me-pedia.org/wiki/Herpesviruseshttps://me-pedia.org/wiki/List_of_herpesvirus_infection_studieshttps://journals.aai.org/immunohori...uman-Herpesvirus-6-Reactivation-Mitochondrialhttps://www.mdpi.com/2076-0817/6/1/2/htm
Is there any reason to be hopeful that Pritelivir, a helicase-primase complex inhibitor, will do something for CFS that Valtrex does not?

Pritelivir https://en.wikipedia.org/wiki/Pritelivir
Valtrex/Valaciclovir https://en.wikipedia.org/wiki/Valaciclovir

It is said here that miR-AU14 produced by HHV will require specifically targeted 'antagomir' therapy

Per GPT
Regarding the ability to enter the CNS, both drugs can cross the blood-brain barrier and reach the central nervous system (CNS). However, pritelivir has been shown to have a higher CNS penetration compared to valacyclovir.

 

[Hip]

Is there any reason to be hopeful that Pritelivir, a helicase-primase complex inhibitor, will do something for CFS that Valtrex does not?

Sometimes you just don't what the benefits might be until you try the drug.

 

[Wishful]

Pretty much anything can be a possible treatment for ME. Whether a specific drug is significantly more likely to work than a drug picked at random, or a food picked at random is a different question ... and much harder to answer.

The main reason I don't think it is likely to help is that while viral infection can be a trigger for ME, blocking a trigger after the 'bullet has left the gun' doesn't do anything to fix the bullet hole. It might help if a person was borderline ME (can switch back to non-ME easily) and stays in the ME state because of continual triggers. Some people find that current viral infections make their ME symptoms more severe, so antivirals might help those people. However, some PWME experience reduced ME symptoms while having a viral infection.

So, my take on it is that Pritelivir might help your ME, or it might do nothing, or it might make your ME worse, and there's really no way to tell in advance. I can't absolutely rule out that Pritelivir wouldn't help my ME, but I'd rate it as a 1/<very, very large number> chance, so I'm not tempted to spend money on it. If it was free, I'd have to check the chance of side effects, because I'd rate the chance of success so low that even a moderately low chance of serious side effects might make it a bad gamble.

Nothing I've seen so far convinces me that ME is due to ongoing viral (or other microbe) infection. The existing evidence more strongly convinces me that it isn't due to that. Pritelivir might help a particular ME patient, but it might do so by some mechanism unrelated to antiviral activity (the molecule just happens to have the right characteristics to block or enhance some reaction).

 

[Hip]

There is a modified version of Pritelivir in development called IM-250, which appears to be able to target both active and latent herpes simplex virus infection:

Treatment of mice lethally infected with a strain of HSV-1 increased survival, and treatment of guinea pigs latently infected with HSV-2 prevented recurrent disease. Thus, IM-250 is an attractive candidate helicase-primase inhibitor that merits further development as an HSV therapeutic.

Source: here

I could not find any info on how helicase-primase inhibitors can target latent infections though.



This article explains the difference between Pritelivir and IM-250:

IM-250 targets a different enzyme, helicase-primase, which HSV uses to unwind DNA as it replicates itself.

IM-250 is not the first compound to take aim at this target, says Gerald Kleymann, founder and CEO of Innovative Molecules, the company that spearheaded the development of IM-250.

Pritelivir, a small molecule in Phase 2/3 clinical trials for drug-resistant HSV, also targets helicase-primase. But that molecule, which has been in development for nearly 20 years, has off-target effects that have been attributed to the molecule’s sulfonamide group.

Innovative Molecules’ chemist Christian Gege hypothesized that swapping the sulfonamide for a sulfoximine might eliminate those off-target effects. Chemists at the company also tweaked an aromatic group on pritelivir to make their drug candidate more likely to enter the central nervous system (CNS), where it could go after latent HSV.

The resulting compound, IM-250, prevented death in mice given lethal doses of HSV-1. In guinea pigs, IM-250 reduced symptoms of HSV-2 infection and prevented the disease from recurring, even after the rodents were no longer taking the compound.

IM-250 might be interesting for fibromyalgia patients, as Dr Pridgen's work suggests herpes simplex infection in various nerve ganglia is the basis of fibromyalgia. He successfully uses an anti-HSV protocol of Famvir 250 mg + celecoxib 200 mg twice daily to treat fibromyalgia.

 

[heapsreal]

Pritelivir is it actually approved yet ie finished all its clinical trials?
I've only just done a quick google search and all I can find is info about its use in different clinical trials for hsv 1 and 2.
It sounds interesting if it crosses the BBB. Is there research on it being effective on other herpes viruses varicella, ebv, cmv, hhv6?
The thing that frightens me is that it's a new drug, so it will be ridiculously expensive. I just look at the cost of valcyte 15yrs ago and I would have thought it would have been a cheap drug by now but......

 

[Forummember9922]

Pritelivir is it actually approved yet ie finished all its clinical trials?
I've only just done a quick google search and all I can find is info about its use in different clinical trials for hsv 1 and 2.
It sounds interesting if it crosses the BBB. Is there research on it being effective on other herpes viruses varicella, ebv, cmv, hhv6?
The thing that frightens me is that it's a new drug, so it will be ridiculously expensive. I just look at the cost of valcyte 15yrs ago and I would have thought it would have been a cheap drug by now but......

You can buy Amenalief, a mostly similar drug online and I think with normal dosing would run you 800-1000 a month, but Pritelivir would be better targeted. You can currently also make a terrible life decision and buy Pritelivir powder from China. If you are uber rich you could buy it from the legit research sites but that would be very expensive.

The issue with Pritelivir is once it hits market (next year or year after) it would only be for immunocompromised people because that's what the completed clinical trials focused on first. That being said I am hopeful that once market happens people can more affordably get it online from overseas.

Theres just not enough data on Pritelivir as it would work on EBV or other herpesviruses but I would guess there would be some crossover effect. Maybe someone more knowledgeable would have a better answer about that

From Chat GPT :
While pritelivir is primarily being studied for its activity against herpes simplex virus (HSV), there is limited evidence to suggest that it may also have some activity against Epstein-Barr virus (EBV).

One study published in 2019 evaluated the activity of pritelivir against EBV in vitro (in cell cultures). The study found that pritelivir was able to inhibit EBV replication in some of the cell lines tested, although the effectiveness varied depending on the cell type and viral strain.

 

[heapsreal]

You can buy Amenalief, a mostly similar drug online and I think with normal dosing would run you 800-1000 a month, but Pritelivir would be better targeted. You can currently also make a terrible life decision and buy Pritelivir powder from China. If you are uber rich you could buy it from the legit research sites but that would be very expensive.

The issue with Pritelivir is once it hits market (next year or year after) it would only be for immunocompromised people because that's what the completed clinical trials focused on first. That being said I am hopeful that once market happens people can more affordably get it online from overseas.

Theres just not enough data on Pritelivir as it would work on EBV or other herpesviruses but I would guess there would be some crossover effect. Maybe someone more knowledgeable would have a better answer about that

From Chat GPT :
While pritelivir is primarily being studied for its activity against herpes simplex virus (HSV), there is limited evidence to suggest that it may also have some activity against Epstein-Barr virus (EBV).

One study published in 2019 evaluated the activity of pritelivir against EBV in vitro (in cell cultures). The study found that pritelivir was able to inhibit EBV replication in some of the cell lines tested, although the effectiveness varied depending on the cell type and viral strain.

I'd think if it works on hhv1 and 2 just like other antivirals it should have effects on other herpes viruses.
I wouldn't be confident on it getting cheaper very soon. As my example above with valcyte, which has been on the market for some time, even its generic version from India is priced out of most people's reach.

 

[Wishful]

This old poll ( https://forums.phoenixrising.me/threads/poll-what-triggered-your-cfs-me.28840/ ) found that <45% of people felt that a viral infection was the trigger for their ME. There seem to be plenty of other triggers for ME. I believe that ME is mostly triggered by immune system activation, and the cause of that activation isn't all that important.

If we had a reliable test for ME, we could get somewhat reliable results for how many patients are actually treated or cured by antivirals. Only somewhat, because if the antivirals require 2 years to see results, there are a lot of potential other factors that could have caused the improvement. Body scans for DNA/RNA fragments from viruses, even hidden or inactive, might be more useful, since antivirals would reduce those levels, and the correlation would be between ME severity and viral content.

 

[Rvanson]

Pretty much anything can be a possible treatment for ME. Whether a specific drug is significantly more likely to work than a drug picked at random, or a food picked at random is a different question ... and much harder to answer.

The main reason I don't think it is likely to help is that while viral infection can be a trigger for ME, blocking a trigger after the 'bullet has left the gun' doesn't do anything to fix the bullet hole. It might help if a person was borderline ME (can switch back to non-ME easily) and stays in the ME state because of continual triggers. Some people find that current viral infections make their ME symptoms more severe, so antivirals might help those people. However, some PWME experience reduced ME symptoms while having a viral infection.

So, my take on it is that Pritelivir might help your ME, or it might do nothing, or it might make your ME worse, and there's really no way to tell in advance. I can't absolutely rule out that Pritelivir wouldn't help my ME, but I'd rate it as a 1/<very, very large number> chance, so I'm not tempted to spend money on it. If it was free, I'd have to check the chance of side effects, because I'd rate the chance of success so low that even a moderately low chance of serious side effects might make it a bad gamble.

Nothing I've seen so far convinces me that ME is due to ongoing viral (or other microbe) infection. The existing evidence more strongly convinces me that it isn't due to that. Pritelivir might help a particular ME patient, but it might do so by some mechanism unrelated to antiviral activity (the molecule just happens to have the right characteristics to block or enhance some reaction).

In 26 years, they dont even truly know what causes ME/CFS. And the onlything that has helped is Ampligen, which is quite expensive,

 

[Rvanson]

Pritelivir is it actually approved yet ie finished all its clinical trials?
I've only just done a quick google search and all I can find is info about its use in different clinical trials for hsv 1 and 2.
It sounds interesting if it crosses the BBB. Is there research on it being effective on other herpes viruses varicella, ebv, cmv, hhv6?
The thing that frightens me is that it's a new drug, so it will be ridiculously expensive. I just look at the cost of valcyte 15yrs ago and I would have thought it would have been a cheap drug by now but......

It doesnt work like that. I'm using a MAOI med that over 60 years old. The cost for one month is over $100 dollars with insurance. Go figure!

 

[Wishful]

And the onlything that has helped is Ampligen, which is quite expensive,

For me, cuminaldehyde worked wonderfully (cured my PEM), and is quite cheap ... but I still don't know how it worked. I doubt that it was working on viruses, since it was quick to start working (few hours) and switched PEM on and off, rather than dose-dependent. It's not impossible that it interfered with some viral action, but that theory would probably have the action vary more, due to varying viral load. Other treatments that have worked for my general ME symptoms, such as LDN, T2, and carnitine seem unlikely to all affect viral infections, and all the other factors that worsen my general ME symptoms are also unlikely to work via a viral route. Overall, I'm just not convinced of ME being due to ongoing viral infection. Severity being worse than baseline due to a viral infection is much more plausible. So, while I accept that antiviral treatments might reduce some ME symptoms for some people, I think temporary reduction during treatment is more likely than post-treatment reduction, and also more likely than full remission.

I think the interest in antiviral treatments for ME is mainly due to wishful thinking (not this Wishful's thinking ), since there aren't any other candidates for a 'magic bullet'. Since the treatments are expensive and hard to obtain, they're like rhinoceros horn in earlier times: that ingredient that is so rare that you don't know anyone who has tried it and can say that it didn't work, while you hear plenty of anecdotal claims that it does work.

 

[heapsreal]

It doesnt work like that. I'm using a MAOI med that over 60 years old. The cost for one month is over $100 dollars with insurance. Go figure!

I don't think anyone knows how it works. I hope I'm wrong and it becomes just as cheap as valtrex is within a short period of time
It was 20yrs ago I was hoping valcyte was going to be a cheap drug by now so more people like us could take advantage of it but ......

 

[Rvanson]

I don't think anyone knows how it works. I hope I'm wrong and it becomes just as cheap as valtrex is within a short period of time
It was 20yrs ago I was hoping valcyte was going to be a cheap drug by now so more people like us could take advantage of it but ......

Big Pharma needs to be taken down for all the profits they make on old mediations.

 

[heapsreal]

Big Pharma needs to be taken down for all the profits they make on old mediations.

The company that make valcyte got pretty shitty when India started making generic valcyte aka valgan. It is cheaper than valcyte but still expensive for the average person to afford. I don't think India come under the pharma patent laws of America or they just ignored them???

 

[Forummember9922]

I see that hhv6, ebv, and cmv also contain the helicase primase. Cross effectiveness with Pritelivir would be speculative but I dont see why it would be impossible. But the non requirement of reactivation sounds interesting.

“As for reactivation, Valtrex requires viral reactivation to be effective. This means that it only works when the virus is actively replicating. In contrast, pritelivir can inhibit viral replication even when the virus is in a latent state.”

The helicase primase of different herpesviruses or at least the associated proteins are not identical.

 

[SWAlexander]

different herpesviruses or at least the associated proteins are not identical.

Now, when we say that the "helicase primase of different herpesviruses or at least the associated proteins are not identical," we're referring to the fact that different herpesviruses, although related, have variations in their genetic sequences that code for these enzymes. This can result in structural differences in these proteins and potentially affect their interactions with other viral and host proteins. The variations might be minor, but they can have significant implications for the activity of these enzymes, the immune response they trigger, their role in the virus's ability to establish latency, reactivation from latency, and how they can be targeted by antiviral drugs.

For instance, the helicase-primase complex in Herpes Simplex Virus (HSV) might have a slightly different amino acid sequence or three-dimensional structure compared to the one in Varicella-Zoster Virus (VZV), even though both are members of the herpesvirus family. These differences can influence how the enzyme functions and how the virus replicates and responds to antiviral medications.

pritelivir can inhibit viral replication

Conclusions: https://www.nejm.org/doi/full/10.1056/NEJMoa1301150​

Pritelivir reduced the rates of genital HSV shedding and days with lesions in a dose-dependent manner in otherwise healthy men and women with genital herpes. (Funded by AiCuris; ClinicalTrials.gov number,