New protein therapy shows promise as antidote for carbon monoxide poisoning | Hacker News Reader

New protein therapy shows promise as antidote for carbon monoxide poisoning

medschool.umaryland.edu

227 pointsbreve57 comments

Here's the full sequence of the protein, found in the supplement [1]

KSSEPASVSAAERRAETEQHKLEQENPGIVWLDQHGRVTAENDVALQILGPAGEQSLGVAQDSLEGIDVVQLHPEKSRDKLRFLLQSKDVGGSPVKSPPPVAMMINIPDRILMIKVSSMIAAGGASGTSMIFYDVTDLTTEPSGLPAGGSAPSHHHHHH

It is a protein encoding the PxRcoM-1 heme binding domain with C94S mutation and a C-terminal 6xHis tag (RcoM-HBD-C94S)

[1] https://www.pnas.org/doi/10.1073/pnas.2501389122#supplementa...

Thanks for that sequence, I can really picture it now

You can search for it here: https://alphafold.ebi.ac.uk/search/sequence/KSSEPASVSAAERRAE... and in principle get the AlphaFold predicted structure (I couldn't find an experimentally determined one). However, like nearly all EBI resources, the web server timed out before I could get a link to the prediction.

Isn't it strange to see protein codes spreading the same way magnet links or AACS encryption keys might.

If you want to download SARS-CoV-2, here you go: https://www.ncbi.nlm.nih.gov/nuccore/NC_045512.2

That doesn't look right. I think the problem is in the last quarter. Exercise for the reader.

This looks like an puzzle input to a day from Advent of Code.

How hard is it to manufacture once you know the sequence?

> Infused in the bloodstream, scavenger hemoproteins like RcoM-HBD-CCC rapidly bind to carbon monoxide molecules, reducing the time it takes to clear half of the carbon monoxide in the blood to less than a minute, compared to more than hour with pure oxygen therapy and five hours without any treatment.

I can see a market in selling this to urban cyclists..

I've seen people doing that get quite a bit of exhaust fumes to the face.

Breath control is an underrated skill.

This research was funded by multiple NIH grants, a Department of Defense grant, and the Martin Family Foundation.

The existing methylene blue substance is also effective in cases of CO poisoning.

1933 paper:

https://journals.physiology.org/doi/abs/10.1152/ajplegacy.19...

"Methylene Blue as an Antidote to CO Poisoning", Matilda Moldenhauer Brooks

This paper is interesting but I want to point out there is a difference between a research paper showing that something is hypothetically feasible and something that is actually useful clinically.

Clinically, methylene blue is used to treat a different condition, methemeglobinemia and is not used to treat carbon monoxide poisoning which relies on hyperbaric oxygen therapy.

The researcher used non-human animals; it worked on them.

The hypothetical part was only that it might also work on humans.

In any case, it seems the result was good enough as a clinical trial from the point of view of veterinary medicine, in regard to those specific types of animals.

We really shouldn't be taking chemicals used on animals for veteran purposes and use them on humans too. For example, ivermectin. It's a drug meant for horses similar to another horse tranquilizer, ketamine. Can you imagine a human taking ivermectin or ketamine?!? I remember during COVID people were shooting up horse medicine and it was just really bad and upsetting, like these people were crazy. I wish Kamala had won and would have banned this horse medicines like ivermectin.

And now this whole methylene blue thing, RFK takes methylene blue. I mean, guys, this isn't even a horse veteran medicine, it's basically ink used to stain cells. I'm sorry, but everything that has an ink or pigmented color it, there is no way on earth it has a medicinal purpose. I mean. It's ink, nothing more.

> We really shouldn't be taking chemicals used on animals for veteran purposes and use them on humans too.

While I totally agree in principle, the specific substance in question (methylene blue) is used on humans already (or should I add was used, at the time of the 1933 study), and for a related emergency purpose: fixing hemoglobin that is poisoned in a certain way, giving rise to a condition called methemoglobinemia.

> And now this whole methylene blue thing, RFK takes methylene blue.

I have no idea about that; I don't follow tabloid stuff.

Methylene blue isn't a now thing; it's been known for a hundred years or more.

> there is no way on earth it has a medicinal purpose

You might be in for a surprise when you do a 15 second web search on it.

RFK playing around with methylene blue doesn't mean anything. If he happens to ascribing to it properties it doesn't have and using it for situations for which it has not been proven, he's engaging in dangerous quackery.

People kill themselves with fentanyl, yet it's an important drug, and on the World Health's Organization list of Essential Medicines: https://list.essentialmeds.org/ (scroll down to the F section).

Oh, look what else is in this list of essential medicines! Methylthioninium chloride. A.k.a. methylene blue.

Yet here you are, claiming that there is no way it has a medicinal purpose?! But you're sure you are smarter than that RFK.

> Can you imagine a human taking ivermectin or ketamine?!?

While I can only believe the ivermectin stuff because it happened (and the crossover of people who took it is pretty strong with people likely to think drinking bleach cures autism…), I 100% can believe people take ketamine because I have, and I will again - it’s fun!

Note to the curious: always do your homework. Start at Erowid and learn about any new drug, be sure to get reliably safe drugs, and the golden rule (via Rick and Morty during a Deadmau5 NYE of all places): you can always take more drugs, but you can never take less.

CO poisioning is one of those strange cases treatable using scuba diving. Recompression therapy, which can be theoretically aped under water, can be like magic. In some cases the patient just wakes up like nothing is wrong. No drugs. No invasive treatment. Get deep enough and hemoglobin isnt totally necessary for getting O2 where it needs to be.

https://www.ncbi.nlm.nih.gov/books/NBK470531/

I guess CO kills you because it sticks to a protein (Hemoglobin), this is a protein that it binds even tighter to.

What I find hilarious though is that my RSS reader loves to show me articles about ways of turning the harmful gas CO2 into the useful gas CO, back when I was a kid it was the other way around!

not very on topic, but for those who missed one of the more surreal reddit threads in history:

- [MA] Post-it notes left in apartment [0]

- and the update from OP a while later [1]

[0]: https://www.reddit.com/r/legaladvice/comments/34l7vo/ma_post...

[1]: https://www.reddit.com/r/AskReddit/comments/49zfvb/what_is_t...

It looks like he found a note in his room and see some strange thing in the window, and someone somehow says it's CO but it may be that the OP has unrelated hallucinations. Is this a symptom of CO poisoning? I think you only get sleepy, faint and die.

Chronic exposure can lead to memory loss, yes. You're describing the symptoms of acute exposure.

Reading in a bit more, the second post links to a comment thread where further down they talk about post-it notes.

The original thread about the post its had some updates along the lines of: someone in comments suggested OP get a CO detector. OP says “ya know, I have one. Maybe I should take it out of the box and plug it in.” Later OP said their detector rated the CO at 100ppm! They went to the hospital lol.

Last update I saw was four months after - OP was guessing their recovery would go on for another year, and there was likely some permanent damage but overall they felt confident at getting back to 80%, maybe even 99%.

CO exposure is accumulative. If you’re around an intense source of it you’re toast. But with a small point source or decent ventilation it kills you slower.

And your body produces new blood cells every day, so minor sources like wood smoke or burning a candle don’t dose you enough to be a problem, unless perhaps your day job is as an athlete.

Also looks like the half-life of CO in the blood is around five hours.

How is this administered? Seems like a crucial detail to omit.

> This has the potential to become a rapid, intravenous antidote for carbon monoxide

So intravenously, presumably.

You can spread it on bread, melt it over pancakes, rub it all over corn on the cob, put it in baked potatoes, etc, promise!

This looks like a therapy you can only get once in your life, after which it has acted like a vaccine and your immune system would react to it.

Typically, protein therapeutics are "humanized" before being pushed through the drug approval process. Part of that is ensuring that the therapeutic isn't extremely likely to trigger an immune response. It's a nontrivial problem.

Those are usually antibodies, aren't they? This isn't an antibody.

https://en.wikipedia.org/wiki/Humanized_antibody

The same rules apply to any protein therapeutic.

The same techniques, however, do not. So how does one humanize an arbitrary protein?

If getting carbon monoxide poisoning once isn't enough to make you invest in a few detectors then I don't know what will

>New Protein Therapy Shows Promise as Antidote for Carbon Monoxide Poisoning

So Shatner was right all along: not only is Promise Margarine good for lowering your cholesterol level, but it can also treat carbon monoxide poisoning! And it tastes like butter, promise.

https://www.youtube.com/watch?v=n3wf717fKFE

I don't see a relation of any kind and I hate commercials maybe more than anybody else, but it's always a good time for a funny one with Shatner :)

Sheez, I can't believe I have to explain that Shatner shows Promise as antidote for high cholesterol too.

He just played New Orleans. Somebody should’ve been throwing tubs of Promise margarine at the stage.

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