Would Favipiravir be effective against Coxsackie virus?

[Swim15]

I like to think I’m somewhat medically inclined as far as reading through literature but I’ve been unsure as to the info I’ve found so far.

Does anyone know if favipiravir would be potentially effective against Coxsackie virus?

 

[Pyrrhus]

In theory yes, but in practice no, it's not.

Don't waste your time on it.

 

[Hip]

From what I am able to calculate (see below), favipiravir might have some very mild effects against all coxsackievirus B serotypes, except CVB4 (which favipiravir is ineffective for). But probably too mild to have a useful clinical effect.


This study found favipiravir has an in vitro antiviral against all coxsackievirus B, except CVB4.

The study found the in vitro favipiravir concentration which prevents 50% of the cell death due to viral infection, the ED50, is 141 μM for CVB3 (with similar values for other CVBs). See Table 1:

Source: A preclinical assessment to repurpose drugs to target type 1 diabetes-associated type B coxsackieviruses



So at free plasma concentrations of 141 μM, you get 50% inhibition of CVB3 (that's not very much, because decent commercial antivirals typically provide around 90% inhibition or more, ie, they reduce the infection by at least 10-fold).

This article says the peak blood plasma level (the Cmax) for the recommended dosing schedule of favipiravir is 51.5 ug/mL, which equates to 328 μM. That's the peak plasma level; the average level will be lower.

The plasma protein binding of favipiravir is 54%, which means that you lose 54% of the drug in you blood to protein binding. So the unbound free peak favipiravir concentration in the blood will be 328 * (100 - 54) / 100 = 151 μM.


So when you take the standard oral dose of favipiravir (normal dosing is 600 mg twice daily), you get a peak free plasma concentration of 151 μM. But the average free plasma concentration will be quite a bit lower.

So at the peak plasma level, you are just about matching the ED50 141 μM concentration used in vitro. But you really need to go a few times higher than the ED50 to get a decent antiviral effect.



It's interesting though that favipiravir has a broad-spectrum antiviral effect against RNA viruses in general. That means it should have very mild effects against coxsackievirus B as well as echovirus.

It's antiviral mechanism of action is via Inhibiting RNA polymerase, preventing replication of the viral genome. Ref: 1

If it were a cheap drug, it might be worth trying, just to see if there were some mild benefits for enterovirus-associated ME/CFS. But at the cost of $12 for just one 200 mg tablet (and you need 6 of these tablets a day), it doesn't really seem like a worthwhile experiment.

 

[Swim15]

Interesting...it seems like some of those other meds may be viable at first glance although I’m guessing protein binding or other factors limit the ability of them in their antiviral capacity.

So it sounds like there’s essentially no options for Coxsackie besides the treatments that Dr Chia uses? Any potential for ozone?

 

[Swim15]

What is guanidine hydrochloride? My brain is a little fried on my knowledge of nucleic acids but is there a potential for treatment?

 

[Hip]

Interesting...it seems like some of those other meds may be viable at first glance although I’m guessing protein binding or other factors limit the ability of them in their antiviral capacity.

Yes, I've done similar calculations on some of the other drugs, and unfortunately it turns out that due to factors like the maximum safe dose and protein binding issues, you just can't match the concentrations used in vitro.

Prozac is actually a reasonable antiviral for coxsackievirus B, if you do the calculations. But I think only for infections in the brain, as Prozac accumulates in the brain at far higher levels than the rest of the body.

But disappointedly, Dr Chia tried Prozac for his enterovirus ME/CFS patients some years back, but I never heard of any success stories.

Guanidine is a potent enterovirus antiviral in vitro, but due to severe toxicity, cannot be used in humans.

So it sounds like there’s essentially no options for Coxsackie besides the treatments that Dr Chia uses?

I systematically went through the dozens of enterovirus antiviral substances I listed in this post, trying to find ones which might be effective in vivo, using the same calculation as I did above (it took months of work!). But unfortunately I found nothing that was potent in vivo, even though many substances were pretty potent in vitro.


The only thing that might be promising in that list is an obscure anti-cancer compound called OSW-1 (a natural substance from bulbs of the Ivory Coast lily). OSW-1 is an incredibly potent broad-spectrum antiviral in vitro, with an EC50 concentration of just 0.0021 μg/ml.

Typically the EC50 for viable antiviral substances is in the range of say 0.1 to 10 μg/ml, so you can see that OSW-1 is potent in tiny amounts. Although if OSW-1 turns out to have a high plasma protein binding, this can weaken its effects in vivo.

Unfortunately I could not find any sources of OSW-1 that sell to the public, nor any animal studies, nor any information about its safety. And Ivory Coast Lilies only contain a very tiny amount of OSW-1, just 0.0027%.

 

[Swim15]

@Hip appreciate it, you’ve done a lot of good legwork. Ah what desperation will do.

I’m not sure if you took bioavailability into account or if you considered an injectable form of any of the things above? I can compound sterile injections and do so frequently so I’m starting to look at something like that - not sure if it would change any of your math but at this point I’ve got nothing left in the world to do but try.

Astralagus as an injection looked somewhat promising...may look into that and a few others in combo with oxymatrine maybe

 

[Swim15]

Also do you have any idea what he impact would be of combining multiple antiviral drugs?

If one only has, say, 30-50% inhibition at an attainable concentration in vivid then what if 5 or 6 of those were combined?

 

[Hip]

I’m not sure if you took bioavailability into account or if you considered an injectable form of any of the things above?

If you have drug with low oral bioavailability, certainly you could get a higher blood concentrations if you inject it.

But in general, I am not sure if that would make much difference, because in most cases it's the maximum safe dose of the drug or substance which limits you.

If the max safe oral dose of a drug creates a blood concentration of X μg/ml, then that would be the maximum safe blood concentration, and even if injecting, you would not want to go higher than X μg/ml, if you are going to remain in safe limits.

Like for example Prozac: the max safe oral dose is 80 mg, and it can be dangerous to go much higher than that, as overdose symptoms include seizures and hallucinations.

Also do you have any idea what he impact would be of combining multiple antiviral drugs?

I think the antiviral effects should in principle be additive, but it's hard to find any substances which are even mildly antiviral in vivo for enterovirus.