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Saturday, March 21, 2020

Finally, I Had Time To See Why An Anti-Malarial Drug Might Be Effective In Treating Wuhan Flu -- March 21, 2020

Updates

April 4, 2020: Trump wins again. LOL.

Original Post

First of all, no one knows if chloroquine will work or not.

But most agree that the CDC is not being a bit helpful by saying that we need to have "controlled" studies before recommending the use of chloroquine to treat Wuhan flu.

The CDC, no doubt, proposes a "controlled" study that will take about five years. And then another year for the scientific paper to be peer-reviewed before it is published. 

The tail is truly wagging the dog.

From wiki, before we even get started:
Chloroquine was discovered in 1934 by Hans Andersag. It is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system. It is available as a generic medication.
The wholesale cost in the developing world is about US$0.04. In the United States, it costs about US$5.30 per dose. [Why does that not surprise me?]
Now, connecting the dots:

How does the Wuhan flu virus get into our cells in the first place? Via lysosomes.

From wiki:
Chloroquine is also a lysosomotropic agent, meaning it accumulates preferentially in the lysosomes of cells in the body.
The pKa for the quinoline nitrogen of chloroquine is 8.5, meaning it is about 10% deprotonated at physiological pH as calculated by the Henderson-Hasselbalch equation.
This decreases to about 0.2% at a lysosomal pH of 4.6. Because the deprotonated form is more membrane-permeable than the protonated form, a quantitative "trapping" of the compound in lysosomes results. (A quantitative treatment of this phenomenon involves the pKas of all nitrogens in the molecule; this treatment, however, suffices to show the principle.)
The lysosomotropic character of chloroquine is believed to account for much of its antimalarial activity; the drug concentrates in the acidic food vacuole of the parasite and interferes with essential processes. Its lysosomotropic properties further allow for its use for in vitro experiments pertaining to intracellular lipid related diseases, autophagy, and apoptosis.
The Reader's Digest version:
The cells involved in the immune process in the human body preferentially take up the coronovirus via lysosomes -- sort of a Trojan horse virus if you will. Chloroquine preferentially degrades lysosomes from doing their job.
How Fido hears this: "blah, blah, blah, horse, blah, blah, blah."


If this works, tell me again how denying a 4-cent-pill to humanity was the right response to a pandemic?

By the way, if this works, it will be interesting to see who first connected the dots. I find this absolutely intriguing.

It appears it's a bit like a drug used to treat cancer. It requires enough of the drug to stop the Wuhan flu virus / stop the cancer without harming the patient. In other words, for chloroquine to work, one must use it in doses that put humans very, very close to the margin of safety.

Blindness? Once again, back to wiki:
The risk of toxicity is low for individuals without complicating conditions during the first 5 years of treatment using less than 6.5 mg/kg/day of hydroxychloroquine or 3 mg/kg/day of chloroquine, and/or cumulative doses of less than 1000 gram and 460 gram (total dose), respectively. 
Again, I think we are talking about using chloroquine for a month or less. Again, an example of an article with a "sensational" headline that is not helpful at all. Not once does it say how safe this drug is and how it's been used for decades to treat malaria.

I had to recheck to see where the article was published. Bloomberg. Okay. Whatever.

See the CDC pdf regarding chloroquine: the only contraindication -- people with psoriasis should not take chloroquine. The CDC pdf says there is no time limit for taking the drugs -- it can be taken for years. In fact, the CDC pdf downplays all risks. It will be interesting how fast the CDC changes these recommendations and risk warnings.

Wow, this takes me back to my days in the US Air Force and deployments to countries where malaria was endemic. Wow, great memories. Seriously. What I liked best: military physicians and surgeons pushing the envelope when saving lives in a combat zone. 

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