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Loperamide-COVID-19: Loperamide is a Potent inhibitor of SARS-cov-2, COVID-19 virus in vitro

MsDiz

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I guess my question is that if hERG is inhibited without causing torsades (which without medical attention is pretty close to a death sentence) going to induce like cardiac hypertrophy or some other nasty more permanent effect.

Like a month ago I was shown the rough SAR for the hERG binding site. The pharmacophore kind of looked like a slice of pizza pointed upwards, with big aryl or other fatty groups at verticies (especially the bottom 2) and a protonatable tweet nitrogen in the middle. (I'm no med chemist but always love learning simple SAR).
When hERG is inhibited it will cause torsades. You might find this interesting though.

 

Skorpio

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When hERG is inhibited it will cause torsades. You might find this interesting though.


That's interesting, didn't know about it but makes total sense when comparing to sulfonylurea inhibition of ATP sensitive K channels to increase insulin release.


I feel in the interest of harm reduction this needs to be said even if it is really obvious: nobody should be using hERG channel blockers to control glucose levels.
 

MsDiz

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That's interesting, didn't know about it but makes total sense when comparing to sulfonylurea inhibition of ATP sensitive K channels to increase insulin release.
I’m down a deep genealogy hole with my PhD and the gene mutation that causes issues with hERG was something I’ve looked at. It really is quite interesting although I’m a nerd.
 

Skorpio

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I’m down a deep genealogy hole with my PhD and the gene mutation that causes issues with hERG was something I’ve looked at. It really is quite interesting although I’m a nerd.
Def feel free to post shit like this in the nspd journal article thread. I liked the scale of the paper, going from observational in humans to drug and siRNA in mice and cell lines.

One of the references showed that long qt2 (the one from hERG inhibition) caused the T wave to look jagged. Interesting little diagnostic tidbit.

 

MsDiz

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Def feel free to post shit like this in the nspd journal article thread. I liked the scale of the paper, going from observational in humans to drug and siRNA in mice and cell lines.

One of the references showed that long qt2 (the one from hERG inhibition) caused the T wave to look jagged. Interesting little diagnostic tidbit.

It really is a good paper. I will definitely add to the thread if you are interested too.

Ive got an eating disorder and I am over familiar with torsades due to presenting with it quite often in the past. (Electrolyte imbalance, hypokalemia.) I’m obviously stable now and have been for years but it’s not something you forget easily. I’ve know a lot of women I’ve been inpatient with who’ve just had SCD. All presenting with torsades with it developing into VF.

Edit to add: Also in response to your posted paper. “Five genes with >170 mutations have been identified”. Don’t I know it! 😂
 
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allone

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It would be interesting to see other people who were were exposed to covid19 while taking daily high doses of loperamide. Did they get sick ? Or were they asymptomatic like me ? If exposed did they develop antibodies which give them lifetime immunity ?
Several years before lope I took zinc and vitamins A and D and elderberry but they did nothing for me. Always got bad colds.

thats because vitamins are useless unless you have genetic disorder deficiency. supplements are useless science based crap in general
 

Skorpio

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It really is a good paper. I will definitely add to the thread if you are interested too.

Ive got an eating disorder and I am over familiar with torsades due to presenting with it quite often in the past. (Electrolyte imbalance, hypokalemia.) I’m obviously stable now and have been for years but it’s not something you forget easily. I’ve know a lot of women I’ve been inpatient with who’ve just had SCD. All presenting with torsades with it developing into VF.

Edit to add: Also in response to your posted paper. “Five genes with >170 mutations have been identified”. Don’t I know it! 😂
Glad you are stable. How quickly does torsades present from baseline may I ask?

And I'll read pretty much anything posted in the journal article thread but I definately have a preference/bias to papers that are biological in nature.

thats because vitamins are useless unless you have genetic disorder deficiency. supplements are useless science based crap in general


I wouldn't call supplements bad because they are based in science. They are bad because they often are supported by tenuous hypotheses with weak data and rely on placebo effect + regression to the mean for anecdotal evidence.
 

allone

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^ i always get my information about supplements from science articles ONLINE or even magazines. i would assume magazines use ads to generate income so its BS, but most of the articles I see online are science based, NCBI mostly. and yes, Science in general is supported by WEAK DATA AND LAZY QUICK TO MAKE A BUCK SCIENTISTS!
 

SpaceWanderer

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thats because vitamins are useless unless you have genetic disorder deficiency. supplements are useless science based crap in general
Agreed. That and scurvy. A dude in college with me lived off peanut butter sandwiches for 1 year trying to save money. Ended up with vitamin deficiency showing as scurvey among other things. A little vitamin C would have helped him.

Some smart people have been fooled by the vitamin racket. Nobel prize winning Linus Pauling was promoting Vitamin C supplements like a religion. It ended up killing his wife.

Took me a long time and a few 100€ to realise this.
 
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Some smart people have been fooled by the vitamin racket. Nobel prize winning Linus Pauling was promoting Vitamin C supplements like a religion. It ended up killing his wife.
How and the hell did Linus Pauling’s wife die from vitamin C supplements. From what I understand, excess vitamin C is not harmful (even in ridiculously high doses). It just gets pissed and shit out without causing too much harm. I haven’t ever heard of vitamin C ever killing anyone.

Please cite sources for such claims.

Thanks,

🧙‍♂️
 

SpaceWanderer

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How and the hell did Linus Pauling’s wife die from vitamin C supplements. From what I understand, excess vitamin C is not harmful (even in ridiculously high doses). It just gets pissed and shit out without causing too much harm. I haven’t ever heard of vitamin C ever killing anyone.

Please cite sources for such claims.

Thanks,

This was well publicized a few decades ago. My freshmen chemistry teacher talked about it too. He explained why supplements can be harmful in terms of their chemical properties. In fact, they can increase the rate of cancer. He had known Pauling.

From the article I link below it is explained this way:

"How could this be? Given that free radicals clearly damage cells -- and given that people who eat diets rich in substances that neutralize free radicals are healthier -- why did studies of supplemental antioxidants show they were harmful? The most likely explanation is that free radicals aren't as evil as advertised. Although it's clear that free radicals can damage DNA and disrupt cell membranes, that's not always a bad thing. People need free radicals to kill bacteria and eliminate new cancer cells. But when people take large doses of antioxidants, the balance between free radical production and destruction might tip too much in one direction, causing an unnatural state in which the immune system is less able to kill harmful invaders. Researchers have called this "the antioxidant paradox." Whatever the reason, the data are clear: high doses of vitamins and supplements increase the risk of heart disease and cancer; for this reason, not a single national or international organization responsible for the public's health recommends them."

Pauling was a chemist and had a Nobel prize in chemistry, yet he didn't understand the concept that the body needs a certain balance of free radicals to kill bacteria and eliminate new cancer cells. That's how it is with people, even the smartest. They have blind spots like this .

It's well known that Pauling was promoting Vitamin supplements, especially vit C. He claimed it would prevent cancer and add 25 years to the life. He wrote at least one book and many articles telling people to take high doses of vitamin C. You can find some online.

He advised2 the public to take 3000 mg vit C per day. That's 50X the FDA recimmended daily allowance. Pauling and his wife were taking 20000 mg vitamin C per day.

After a few years of this heavy vitamin C intake, his with got stomach cancer and died. But that didn't deter Pauling. He kept up his 20 gram a day vitamin C diet. Several years later he died of prostrate cancer.

Here is a link to an article in the Atlantic that goes into more detail what I said. They also cite several studies that link increased risk of cancer to vitamin C.




And here: http://nutritionandcancer.org/view/nutritionandcancer/oism_nac.pdf

Study gave megadoses of vitamin C to mice. Their rate of cancer doubled. The principal investigator was Pauling's colleague. When Pauling saw the data from the preliminary experiments done in the 1980s, he fired him, shredded the data, and killed all the experimental mice. And he continued to promote megadosing on vitamin C.

 
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allone

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he died at 93.... for real, im very skeptical vitamin c killed him hah. if anything, it probably prolonged his life maybe?? and his wife died at 77. seriously, thats not that bad although it should be the opposite in the world males lives to the 70s and women beyond. well, maybe he did killed her, who will ever know!? put some henbane oil in that vitamin c IV solution, good things are to happen.
but anyway, i did megadoses of vitamin c myself, and i had diarrhea for days! highly UNRECOMMENDed! well, its cleansing, i guess? but im not surprised cancer grows on vitamin c as any vitamin will speed its growth really. whatever healthy cells need, unhealthy ones need too. like giving sugar to a good boy and a bad boy, but the bad boy goes and trashes shit because the sugar just gives him too much energy in the negative way
 

MsDiz

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Glad you are stable. How quickly does torsades present from baseline may I ask?

And I'll read pretty much anything posted in the journal article thread but I definately have a preference/bias to papers that are biological in nature.
Hey, I am so sorry I’m only seeing this now. I didn’t get the notification.

I’ve got a few pics on imgur to put here for you (sorry about the banner, I am on a mobile an I can’t remove it).

I did look out my own notes but I can’t remember the date and there are A LOT on the system that I just don’t have time to look through right now. Sorry!

I couldn’t find a proper long QT to torsades that I found good enough. In hypokalaemia there is a pretty obvious slight depression/inversion of the T wave. In the pics attatched it’s a bit more obvious than in what mines were, I did have very much a long QT, this is long QU interval but I think it’s pretty close. This is a hypokalaemia patient, starting K+ levels were like 1.7.

On the last pic, “Note the atrial ectopic causing ‘R on T’ (or is it ‘R on U’?) that initiates the paroxysm of TdP”. (I really do like that example, I’m saving it for future use.

I used to LOVE reading ECG and EKGs when I was young. Of course back then I would have to take the reading the Dr had kindly given me to the library and look through a few books. God I really was a nerd. Ha!

 

(zonk)

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Wait if pgp has something to do with covid then what would a potent pgp inhibitor like piperine do?
 
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