Post #607: Hydroxychloroquine? Maybe it works. Maybe it even works well.

Ionophore transmitting metal ion across cell membrane.  Source:  Wikipedia

I’m going to keep updating this continuously, so you might check back in a few hours.

Back in Post #562 (March 19 2020), I reviewed the evidence for hydroxychloroquine, as one of three drugs that might prove useful for COVID-19.  Search “An old drug that works in vitro (in a test tube).  Not yet proven in humans, but it sure looks like it ought to work”.  I was flip enough to describe it as “Golly, that’s like “take two aspirin and call me in the morning.”“.

It certainly had potent anti-viral properties in vitro against SARS (2003) and SARS-CoV-2 (COVID-19).  The drug was already known to concentrate in certain organs, including the lungs.  A small study in France suggested some efficacy in humans.  The Chinese had included it as one of very few drugs approved, in that country, for COVID-19.

All the elements of likely effectiveness were in place.  (And, separately, as it turns out, virtually all of those older-line malaria drugs, and the current malaria drug of choice, also have significant anti-viral properties, suggesting some underlying mechanism behind all of them. )

So I’ve been looking for further evidence to pop up.

There are now two separate reports — case studies from one physician, and professional society endorsement — suggesting that it does work.  It’s well worth your while to check out both of them.  One physician says that the drug must be used with zinc to be effective.  That’s a new one on me, and I’d love to understand what the presumed mechanism of action is there.

First, here’s an LA physician.  He’s the guy who says, combine with zinc.  His results sound a little too good to be true, based on the efficacy of other anti-virals in late-stage illness.  But you never know.  I’m going to spend a little time to see if I can track down the presumed mechanism that involves zinc.

Second, here’s no less an authority than the American Thoracic Society of New York (a physician professional society) endorsing off-label use for severely ill COVID-19 patients.  (The actual guidance document, referenced there, is literally from the American Thoracic Society.)

Just thought I’d pass along a little good news for a change.  And let you know that, despite what you may read, yes, there was a good chance this would work.  But nobody anticipated the results that the LA doctor reported, with combined with zinc.  Don’t get your hopes up, but he does seem to be a legit doc, legitimately taking care of COVID-19 patients.

Be aware that there are also studies showing no effect.  So the evidence is far from crystal clear.  No less an authority than Dr. Anthony Fauci says we should not assume that this is a “knockout drug”.

But I have to say, for that LA doc to say — eight hours later the patients taking the drug in combination with zinc were symptom-free.  That’s a strong claim and is easily tested.  And a requirement for requirement that something else be present — something already found in varying levels in the body — would be a plausible way to explain variations in success rates across studies, and then a claim of huge impact with explicit supplementation.

Update 1:  Well, about that zinc thing.  Sure enough, there was already a clinical trial underway using a combination with zinc.  The don’t do stuff like that at random, so presumably some smart cookie had some understanding of probable mechanism of action.  That was an observational trial for using this drug prophylactically (to prevent healthcare workers from getting coronavirus).  But at the bottom of the listing is a raft of scholarly articles on this.

Update 2:  And here’s an MD from New York who, separately, identified this drug, in combination with zinc, as an effective medication at preventing hospitalization of COVID-19 patients.  It’s always good to see some independent confirmation, even if it’s just a series of 200 cases for one physician.

OK, weirdly, zinc does in fact bind to hydroxychloroquine.  That’s been flagged as a potential drug-drug interaction.

And, it does potentiate the uptake of zinc by human cells, and that response is unique to zinc (as opposed to other metals.).

Apparently the FDA quietly approved the use of hydroxychloroquine for COVID-19 more than week ago, on an emergency basis.  I didn’t know that.  So it’s not even an off-label use now.

Aha!  Here’s an explanation for a potential mechanism right here, based on a couple of scholarly studies — read the comments.  If true, hyroxycholoroquine’s main role in humans is as a zinc ionophore — something that transports zinc ions across the cell membrane and therefore substantially raises within-cell zinc concentration.  Heck, it’s already been demonstrated in vitro

Ah, here’s what an ionophore is.  Interestingly, Wikipedia does not list a single zinc ionophore.

Based on this, if it really is the zinc, any consumable zinc ionophore that concentrates in lung tissue would be helpful.  Makes me wonder if there others that are as effective as hydroxycholorquine.  Makes me wonder if the reason that all those old-line (and current) anti-malarials have the same underlying mechanism of action.

Hilarious:  Quercitin is a zinc ionophore.  That’s a flavonoid, which you first met in my post on folk medicine (Post #552).  In fact, that’s the single most common flavonoid in the diet.  I think I’ll get my order in at Amazon before that’s vacuumed off the shelves.  Pretty sure I’ve got some zinc pills around here somewhere …

Two other zinc ionophores I’ve never heard of, but in vitro anti-viral activity was demonstrated.

So in addition to “eat your fruits and vegetables” (flavonoids), we can add green tea (epigallocatechin-gallate, another flavonoid) and zinc pills to my roster of folk medicines.

That’s not medical advice.  That’s just what I’m going to do, based on the observation that zinc supplementation apparently greatly enhances the effectiveness of hydroxychloroquine, and that zinc apparently does show in-vitro anti-viral effectiveness, if it can be transported into cells in high enough concentration.

Probably can’t hurt, if done in moderation.  Might help.  Why not?