How does hydroxychloroquine ferry Zn++ into cells?

Tags

, , , , , , , , , , , , , ,

The title question is important important in the context of treating covid-19 as an antiviral.  There’s a theory that Zn++ is effective against covid-19 by binding to the RNA dependent RNA Polymerase of the SARS-2 virus.

There’s an article showing that chloroquine is a zinc ionophore, but I haven’t found a mechanism that explains how this happens.

My chemistry is VERY rusty. I had to refresh my understanding of “base” over at wiki, lol. (HC has been called a “weak base”.) A base has one or more of three properties: 1) it donates hydroxide ions into aqueous solution, 2) it accepts protons, or 3) it donates electrons.

It has been suggested by SJF over at The Rational Male (search for “ASD I thought the virus”) that HC increases NH3 somehow. HC has three nitrogens in its structure. One of those would have to be sacrificed, which would destroy the HC. Some enzyme would have to do this. If there was anything like this, it would be in the lysozome. Then the NH3 becomes NH4+, so the lysozomal pH increases. This will shut down the lysozome. But there shouldn’t be any viral material in the lysozome anyway. The lysozome eats viral DNA and proteins. I don’t see any antiviral benefit from alkalinizing the lysozome. (For cancer, this would prevent autophagy, tho.)

But how does HC ferry zinc into cells? (HC is a zinc ionophore, remember?) HC comes as HCS04. HC must therefore have a +2 charge. So HC++ won’t be able to bind to zinc immediately (unless somehow binding to zinc creates a more quantum-mechanically stable product, which seems improbable for a +4 product). Therefore HC must be cleaved somehow, which means that a protein is involved. And HC must gain electrons, which means that a sugar is probably involved. (Glucose and RNA bases are all sugars.) And for those two things to be involved, they must be in close proximity, so a membrane is most likely involved. And the product will end up in an endosome.

So some product of HC cleavage must be the actual zinc ionophore. And if the zinc were carried inside an endosome which is fed by an ACE2 receptor, that would be a good thing because viral proteins could gain access to the endosome and they would help the zinc escape the endosome near the nucleus of the cell before the zinc gets used for cellular functions. The zinc could then bind to the viral RNA polymerase and prevent replication. (I don’t see zinc doing anything directly to viral RNA.)