D, L-lysine acetylsalicylate and glycine Impairs Coronavirus Replication (2016) [pdf] | Hacker News Reader

D, L-lysine acetylsalicylate and glycine Impairs Coronavirus Replication (2016) [pdf]

longdom.org

76 pointswilsonfiifi53 comments

Edit: I accidentally used the stock concentration in my original calculation, updated to the effective dose found.

The average volume of a human is around 62 liters.

The effective concentration for the highest EC50 is 6.71mM. The lowest EC50 is 1.31.

Aspirin DL-lysine as a molecular weight of 326.34.

Therefore, to reach the concentrations used in the study, the average person would have to consume somewhere between 26 and 135g of asprin (from the two molarities above). Way above the maximum safe daily dose, which is 4 grams.

Using the absolute best case scenario- 1.31mM- and an effective volume of 12 liters, that's still 5.1g. Which is /just/ under the max safe dose. At 6.71mM, that's 26g.

Exactly what I came to the comments for... dimensional analysis, done right - you the real mvp! Thanks.

To be more precise: 50 millimolar was the stock concentration, not the concentration used in the experiments. The effective concentrations were between 1 and 7 millimolar.

> The results indicate an effective concentration 50 (EC50) of 1.31 mM for HCoV-229E resulting in a selectivity index (SI: CC50/IC50) of 15.6 as well as an EC50 of 3.69 mM for MERS-CoV, leading to an SI of 15.9, similar to that of HCoV-229E (Figures 2D and 2E). The EC50 for HCoV-229E-infected PBMCs at 24 h was 6.71 mM resulting in an SI of 5.7 (Figure 2F).

And if tlb is right that the volume of distribution is under 12 liters, the dose required in the best case would be approximately the maximum dose of aspirin (4 grams). In the worst case, far more.

That would be 12 325mg aspirins. Which is too much, but almost in the ballpark.

Thanks for catching that. I've updated the math in my comment.

At those concentrations I suspect there is a whole lot of substances that kill the virus (along with the host).

Option B: Or we could raise our blood alcohol level at 60%-70% by volume, apparently that kills the virus :)

Drugs don't spread out evenly through the whole body. For this class of drug, it's bloodstream concentration that matters.

The complex field of pharmacokinetics relates the bloodstream concentration to the ingested amount over time. The simple version uses a "volume of distribution" which, for salicylate, is 11.9 liters for a standard male. [https://sepia.unil.ch/pharmacology/index.php?id=83].

So to achieve the 1 - 7 milimolar concentrations they used would require 3.8 - 27.2 grams of aspirin.

This kills the kidneys

What's the half-life of aspirin in the bloodstream? Probably less than a day, which would significantly increase the dose required to maintain those concentrations.

It seems like this might merit further research as a treatment for severe cases, but it's far too dangerous to be a prophylactic for healthy people.

(And that's all assuming these results on other coronaviruses apply to the new coronavirus that causes COVID-19.)

These calculations aren't helpful at all.

Drugs don't evenly distribute in the body. Some drugs get bound to specific proteins, so the observed concentration is much lower (i.e. higher volume of distribution). Others get concentrated in specific organs once they equilibrate across the body.

Sure, but unless we have some reason to think that this will have some reason to concentrate in the lungs in particular its a quick sanity check. Maybe it does concentrate in the lungs and this'll be a great medicine but a priori we don't have any reason to expect that and this is a reason not to get our hopes up.

Reminds me of this:

https://xkcd.com/1217/

This should be taken down.

Unsafe procedures are proposed and discussed here.

This is a single study and not a recommendation for treatment of anything, esp. the virus causing COVID-19

I wonder if other salicylates would have the same effect, given the research showing that Bismuth inhibits SARS and the fact that Pepto Bismol is bismuth subsalicylate:

https://www.researchgate.net/publication/6193909_Bismuth_Com...

I saw the abstract, and ever since I've been wondering about whether that Bismuth paper includes bismuth subsalicylate as well as citrate, or whether chugging a bottle of Pepto Bismol a day would be a mistake equivalent to aquarium cleaner guy.

On the other hand, if it's the glycine that causes most of the effect, that's a cheap nutritional supplement.

Can someone explain what "D, L-lysine acetylsalicylate and glycine" are in laymen's terms?

I saw some comments mentioned about Aspirin/NSAID. But what's the practicality of this research? Btw, this was dated 2016.

It is a salt of aspirin, in addition to glycine, an amino acid...Lysine is also an amino acid but in this case is part of the aspirin salt.

https://www.drugs.com/international/aspirin-lysine.html

As I understand it... the reason they think they need to have the Lysine is that it it makes the body absorb it better. Please correct me if I'm wrong!

The EC50s in the paper are in the millimolar. These are physiologically irrelevant concentrations.

Irrelevant in the sense that anything will kill baddies at high enough concentrations, but it'll also kill people?

Or irrelevant in the sense that it's totally achievable to do that in people and it won't mess with their bodies too much?

The first one, unfortunately. To reach the concentrations in the paper, you'd have to consume over 1kg asprin.

Pretty sure I used to take L-lysine for cold sores. Maybe it has general antiviral properties.

Certain viruses (herpetic) proliferate in an environment high in arginine, and low in lysine. High lysine/low arginine = suppression of replication.

It's reputed to. It's been an alternative remedy recommended for shingles. Not seen a jot of evidence it works.

I have some glycine. I can get lysine and aspirin. How do I make lysine acetylsalicylate?

Or you could just wait for Ventaleon's [0] inhaled LASAG (D,L-lysine acetylsalicylate • glycine) to be ready.

  [0] http://www.ventaleon.com/news/18-ventaleon-presents-phase-ii-results-with-inhaled-lasag-in-severe-influenza-at-isam-congress-2017

Is there any new information on them? I can't find anything recent about them.

Most recent information on aerosolized LASAG is dated 2018 [0]

  [0] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841227/

Googling those people + the CEO of the company, they all seem to have moved on though. So I wonder if that company is even alive anymore.

I found this https://informaconnect.com/ventaleon-ceo-on-inhaled-drugs-fo... where the CEO said they had enough funding to produce the study but would need funding to move past that. Doesn't look like they got it.

You don't. Don't make your own medicine.

Why? I make some (not illegal, very simple) occasionally. It works great and costs me some orders of magnitude less than it would cost to buy the same amount.

Here's one on Nettle..

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3085190/

And during this out break, we have seen some tentative data that patients on aspirin do worse, and should avoid it.

Wish we knew which way to jump.

This study was done in vitro. If I recall the counterindication of aspirin in C19 patients was accelerating pneumonia or something. So it's possible aspirin does both.

Look with suspicion on any in vitro data. There are so many differences between in vitro and a living organism. Nevermind the fact that in vitro tests usually use concentrations that would never be achieved in the body, a fact usually lost on the public. I’d definitely lean towards the “aspirin is bad with Coronavirus” camp on this one.

Source: Myself, a former tester of in vitro effects.

> Nevermind the fact that in vitro tests usually use concentrations that would never be achieved in the body, a fact usually lost on the public.

But the reason large doses are used in vitro is because it's easier to show that a chemical actually inhibits viral replication if you can slow down replication by 99.9%. But in real life, you might only need to slow down replication by 10% or whatever to meaningfully improve clinical outcomes.

That's true in theory and we should see aspirin doing something in vivo for coronavirus if it did, but we don't. Something else more important seems to be affecting it the other way.

In skimming the article it seems they used 20 mM doses and ranges which is an absolutely enormous amount of anything. We normally considered low uM the range where something is even beginning to be interesting.

Yeah about the in vitro thing.. I'm sure gasoline also kills the corona virus. Unfortunately the patient also goes.

>This study was done in vitro. If I recall the counterindication of aspirin in C19 patients was accelerating pneumonia or something. So it's possible aspirin does both.

Relavent: https://xkcd.com/1217/

Aspirin is a blood thinner it might cause your lungs to bleed once they sustain enough damage to their epithelial layer which might make your pneumonia worse.

According to the Medcram youtube series, NSAIDs in general are known to impair virus replication, but also impair immune function. What is the net result? That is less clear. Many believe that aspirin had a negative effect during the 1918 flu epidemic though.

Video link here: https://www.youtube.com/watch?v=dT6mHi_8V5E

According to https://academic.oup.com/cid/article/49/9/1405/301441, the aspirin doses that were used in 1918 (8.0 - 31.2 g/day) were much higher than what people normally take today (usually a max of 3.6g or so).

Apparently aspirin contributed to fatalities via aspirin poisoning, so it did not necessarily have a direct impact on the virus.

Reference: https://en.wikipedia.org/wiki/Spanish_flu#Aspirin_poisoning

Is there actual good data on aspirin/NSAIDs? Because what I've read was a theory communicated in a letter to the Lancet, and the actual data might suggest the opposite.

You have this backwards. They are saying to stay away from ibuprofen, not aspirin.

Which of course is a theory that is being walked back.

https://science.sciencemag.org/content/367/6485/1434.1

My mistake. Why would I have thought that a cyclooxygenase-inhibiting NSAID would have anything to do with a cyclooxygenase-inhibiting nsaid. These are entirely different kettle of fish, and I am a fool for thinking adverse effects of one would be at all related to the adverse effects of the other.

I was mistaken, and got snarky about it to boot. I was in a shit mood. Sorry.

One of the first victim in Turkey wrote her twitter she was using vinegar and aspirin solution before she passed away. But she had also some permanent sickness which i can not recall. I also wonder how ahcc plays well with it because i have been using since a month and had asymp symtomps since 10 day so far i can say i recovered and my gf shows no symptoms at all (she is also using) atm asked my gp and waiting response him.

In this study the aspirin used is actually a salt of aspirin, tradename is Aspirin I.V.

relevant xkcd: https://xkcd.com/1217/

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