Novel Antiviral Activity of Ethyl 3-Hydroxyhexanoate Against Coxsackievirus B Infection

Hip

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If you are in the EU, you can buy ethyl 3-hydroxyhexanoate (EHX) from Laboratorium Discounter. 25 grams costs €58. 100 grams costs €157.

I've got some EHX on order, and will be trying this antiviral within weeks. It's one of the most interesting new enterovirus antiviral substances I have seen in a while.

EHX is a registered food additive and food fragrance, with a fruity taste similar to grapes.



A mouse study administered 250 mg/kg of EHX twice a day by intraperitoneal injection.

In the group of coxsackievirus B-infected mice not given EHX, 57% died; whereas in the group given EHX, 37% died. So that demonstrates in vivo efficacy of EHX against coxsackievirus B.

The mouse dose of 250 mg/kg twice daily works out as a human dose of 20.3 mg/kg twice daily. So for a 75 kg human, that is a dose of about 1500 mg twice daily.

This paper says the no observed adverse effects level dose (NOAEL) = 13.47 mg/kg daily. So about 1000 mg daily for a 75 kg person is safe and has no adverse effects.

So a daily EHX dose of say 500 mg twice daily would be within the NOAEL safety limits.



Given that the water solubility of EHX is reasonable (17 mg/ml), we can guess that oral bioavailability is going to be good, so injecting EHX may not be necessary, and oral consumption of EHX may be adequate. So one could place a 500 mg dose in a large glass of water and drink it.

Though as with all substances tried experimentally, it would be wise to start with lower doses, and titrate up slowly, observing any side effects that may appear

EHX is a liquid at room temperature, with a density very similar to water (0.97 g/ml), so a 500 mg dose would correspond to 0.5 ml.

The half-life of plant-derived volatile compounds like EHX is short, but in the study, they found that EHX binds tightly to viral proteins, and it remains attached to these proteins up to 48 hours. So its antiviral action in the body lasts much longer that its short half life would suggest. So that's good.



Another interesting thing about the study is that they tested EHX against some enterovirus replicons that the authors engineered. Replicons are similar to non-cytolytic enterovirus. They found EHX inhibits the replicons too. This is good, as it suggests EHX could be effective against the non-cytolytic enterovirus infections found in ME/CFS.

EHX also looks like it may have broad-spectrum antiviral effects against all enteroviruses. If you look at table 1 of the study, this shows the computer-calculated docking affinity of EHX to various viral proteins. You can see that it docks to the viral RdRp proteins of poliovirus and rhinovirus, which are both enteroviruses. So EHX will likely have antiviral effects against a wide range of enteroviruses.



EHX acts as an RNA-dependent RNA polymerase (RdRp) inhibitor.

EHX binds to some non-structural proteins of enterovirus, and in particular, it binds to enterovirus 3D protein, which is the enterovirus RdRp protein. By binding to this protein, EHX blocks its action.

Thus EHX acts as an enterovirus RNA replication inhibitor.



EHX is a volatile organic compound found in fruits, and such compounds can cross biological membranes and the blood–brain barrier. So EHX should have antiviral effects within the brain too.
 

Hip

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The only place we have found which sells EHX to individuals is m Laboratorium Discounter in the Netherlands.

Unfortunately this seller only ships to EU countries, but not the UK, US, Canada, Australia, etc.

But the way around this shipping restriction may be to use a shopping forwarding service to forward your EHX purchase to your home address in the US, UK, etc.

A shopping forwarding service gives you a free personal address in various foreign countries that you can use to receive your shopping items bought in those countries. On receiving your shopping items at this free address, the forwarding company will then forward the items to your home address, typically with low fees not much higher than standard international shipping costs.

The following shopping forwarding companies provide a free personal address in Germany that can be used for shopping:

https://www.mailboxde.com <-- Ships to the US, UK and most of the world
https://www.forward2me.com/warehouses/germany <-- Ships to the US, UK and most of the world
https://www.europemailbox.com <-- Ships to the UK, but does not ship outside of Europe

You just have to register for an account, and they will give you a personal address in Germany. You are not charged any fees for having an account. You then can order some EHX from Laboratorium Discounter in the Netherlands, using this free address.

When the EHX arrives at your personal address at the forwarding company, they will send you an email, and typically give you several different shipping options. You select one option and pay, and then the EHX will be forwarded to your home address.

Note though that shopping forwarding companies have restrictions on the goods they will forward, so it is worth reading their restrictions page. If the forwarding service receives your EHX and then says they cannot forward industrial chemicals, you can tell them that the EHX is not an industrial chemical, but is simply a food additive fragrance (which it is, EHX has the food flavour FEMA number of 3545).

However, there is a chance that the shopping forwarding company will not forward the EHX, so you may then lose your EHX purchase.

Thus it may be an idea to initially buy the smallest 25 gram amount of EHX first from Laboratorium Discounter, just to check that the shopping forwarding company can forward it.



EDIT: I just emailed the German shopping forwarding company www.mailboxde.com to ask whether they can reship EHX, and they told me they can. Their total reshipping cost to the UK is about €20, and to the US is about €30.
 
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Right so tricky to get in the UK. I misse that bit of info on discord. I'd love to try this but the side effects would no doubt prevent me from being able to.

On a side note now that imd have stopped doing testing it's become very difficult to even get a test. I know I've had opportunity to do this before but until very recently I didn't really have the spare money to do it.

So hopefully you've not answered this. Do we know if the ehx will cross the bbb or penetrate the CNS?
 

dylemmaz

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EDIT: I just emailed the German shopping forwarding company www.mailboxde.com to ask whether they can reship EHX, and they told me they can. Their total reshipping cost to the UK is about €20, and to the US is about €30.
thanks for doing the hard work for us @Hip. i plan to order this and give it a trial.

@Pyrrhus i was wondering if this is something you will be trialing given your success with favipiravir? i remember reading (correct me if i’m wrong) that you had lots of success with favipiravir but stopped due to toxicity? do you have any thoughts on this? thank you so much
 

Hip

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I attach the safety review study for EHX to this post.

Anyone considering trying EHX might like to read this safety assessment.

As you can see, the repeated dose NOAEL (no observed adverse effects level) for EHX is 13.47 mg/kg daily.

Though as with any new drug or substance being tested experimentally for ME/CFS, starting at a low dose and titrating the dose up over some days is a good idea.
 

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Oh geez, they actually show a picture of the mice in the study... never seen that before :oh-dear:

I'd like to stay in the loop w/ EHX. Especially those considering taking it. Good stuff!