I like the Zinc + Ionophore therapeutic hypothesis, as Ralph Baric, the godfather of all coronavirus research seems to think this is our go-to treatment; going so far as to test it in cell culture.
Zn(2+) inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture (PMID: 21079686) 2010
The ionophore used in his cell culture study was "pyrithione", which apparently is primarily used in dandruff shampoo, so not applicable for oral medication use. We know Chloroquine is an effective zinc ionophore, as this has been well documented: Chloroquine is a zinc ionophore (PMID: 25271834) 2014
Those applying this combo for COVID figured "why not use hydroxychloroquine" as its the new and improved, safer form. Brilliant! Except for this: Hydroxychloroquine Does Not Function as a Direct Zinc Ionophore (PMID: 35631485) 2022
Wait... What? HCQ isn't a zinc ionophore? Apparently the hydroxyl tail added to chloroquine to make it safer also interferes with penetration of the phospholipid cell membranes. The above report does allude to HCQ possibly getting zinc into the cytoplasm through an alternate mechanism: "Molecular simulations show hydroxychloroquine-triggered helix perturbation in zinc-finger protein without zinc chelation, a potential alternative non-ionophoric mechanism."
OK, so HCQ + Zinc still works, but would an alternate, true ionophore provide superior effect? We've heard quercetin & EGCG are zinc ionophores, and ivermectin has even been branded an ionophore; but how potent is the effect compared to HCQ, or perhaps better yet, old school Chloroquine?
Might there be an even better option? We know Chloroquine was created as a synthetic form of quinine. Might simple quinine be an effective zinc ionophore that is safer than Chloroquine and more effective than HCQ?
Quinine Inhibits Infection of Human Cell Lines with SARS-CoV-2 (PMID: 33918670) "our data indicate that quinine could have the potential of a treatment option for SARS-CoV-2, as the toxicological and pharmacological profile seems more favorable when compared to its progeny drugs H-CQN or CQN"
More on zinc & quinine here: Current Evidence Supporting the Use of Orally Administered Zinc in the Treatment of COVID-19
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Interestingly, influenza, rhinovirus (common cold), and RSV are also "single stranded RNA" virus. Might the Zinc + Ionophore be a cure-all for nearly all respiratory virus? The zinc part is easy, but what is the truly superior ionophore?
I'm having trouble finding out just how effective quercetin and EGCG are at zinc transport into cytoplasm, or evidence quinine might be more effective than these, or as effective as chloroquine, or perhaps more effective than HCQ.
I'm hoping others here might be similarly intrigued. Anyone else want to work on this and see what we can find?
Edited by Dorian Grey, 29 November 2022 - 11:44 PM.