Dr. Philip McMillan, John McMillan
There is an enzyme at the heart of nearly every RNA virus known to trouble human beings, and it has exactly one job. It copies. RNA-dependent RNA polymerase is the photocopier a virus smuggles into a cell, and without it there is no second generation of virus, no third, no spread to the person sitting across the table. Slow that copier down and the outbreak inside a single body slows with it.
Now consider the guest list. SARS-CoV-2 depends on this enzyme. So do the original SARS coronavirus, MERS, and the drab common-cold coronaviruses that come around every winter. Influenza needs it. So do dengue, Zika, yellow fever, the rhinoviruses behind an ordinary sniffle, hepatitis A, norovirus, and, at the grim end of the range, Ebola and Marburg. One target, shared by a set of viruses that otherwise have almost nothing to say to one another.
That kind of overlap is unusual in virology. Most antiviral drugs are bespoke, engineered against a single pathogen and close to worthless against the next, which is why every new outbreak restarts the drug pipeline near zero. Anything aimed at the shared copier would not much care which virus turned up. And such a thing exists, in plain view. Zinc inhibits this enzyme. Laboratory work reaching back to 2010 showed zinc ions shutting down coronavirus polymerase activity in cell culture, and the result has held up in the dish ever since.
So the answer is to go and buy zinc?
Not quite. Zinc on its own runs into a wall.
The problem with the supplement aisle
Zinc only reaches the polymerase if zinc gets inside the cell. The polymerase is inside the cell. The virus is inside the cell. All of it happens inside the cell, and the cell membrane is not a screen door. It decides what crosses and in what quantity, and it does not wave zinc through because there happens to be more of it in the bloodstream.
This is where most public conversation about zinc quietly falls apart.
“A lot of people think you just take zinc. So they will take a zinc supplement, but the zinc is on the outside of the cell. There is no real mechanism to get it inside the cell in the quantities that you need,” said Dr. Philip McMillan.
Swallowing zinc raises serum zinc. Serum zinc is not the same thing as intracellular zinc, and it is intracellular zinc that the mechanism requires. A great many people who dutifully took zinc lozenges through the pandemic were, on this reading, delivering their cargo to the wrong side of a locked door.
A key for a locked door
The missing piece has a name: an ionophore. These are compounds that open a temporary channel through the membrane and ferry a metal ion across. Zinc plus an ionophore is a different proposition from zinc alone, because only the pair actually gets the payload where it needs to go.
The pandemic did test one of these. Hydroxychloroquine has ionophore properties, and that, rather than the political noise it later attracted, was the scientific reason for pairing it with zinc. The trials mostly came back negative. Read carefully, though, they tested one drug at particular doses at a particular stage of illness, usually late, in hospitalised patients whose virus had long since finished replicating and whose damage was immune-driven. A negative result there says something about a schedule. It says less about the mechanism than it first appears.
The point is academic for most readers anyway. Nobody is prescribing hydroxychloroquine outside autoimmune disease, and it carries real side effects.
The compounds that matter here are the ones already within reach. Quercetin, found in onions, apples and capers. EGCG, the catechin in green tea. Curcumin, the yellow in turmeric, and therefore in a decent curry. All three show ionophore activity in laboratory work. All three are sitting in an ordinary kitchen.
What it does, and what it does not
Nothing here kills a virus. Nothing sterilises an infection. The pairing slows the copier, and that is the whole of the claim.
It sounds like a small thing. It is not, because of what the immune system is actually short of, which is not capability but time. The body is already very good at these fights. Once it identifies an infected cell, T cells arrive and shut the copying down for good.
The trouble is the delay before that happens. SARS-CoV-2 is unusually skilled at blocking interferon, the body’s early alarm signal. Silence the alarm and the virus copies itself unopposed for days, seeding tissue and reaching the next person while the response is still being assembled.
Slow the copying through exactly that window and the arithmetic changes. The immune system gets the interval it needs. Peak viral load comes down, which plausibly means a milder course and less virus shed toward everyone else. Buying time is a far smaller claim than curing anything, and it is the one the biology actually supports.
The trial that never ran
In July 2020, a double-blind placebo-controlled protocol pairing zinc with an ionophore was taken to the FDA. Early in the pandemic, with the mechanism already understood, someone tried to run the experiment properly. It appears never to have been completed.
Five years on, the scoreboard reads like this. The mechanism is strong in cell culture and biologically coherent. The clinical evidence in humans is weak and, where it exists, unimpressive: a large trial of zinc with vitamin C found no reduction in symptom duration, and it did not include an ionophore. The direct experiment, zinc paired with an accessible ionophore, given early, in outpatients, remains largely unperformed.
The question was never answered. It was dropped, and a dropped question has a way of being mistaken for a closed one.
Why cheap ideas stay untested
Why has nobody run it?
The unglamorous answer is that trials cost money and money follows patents. Quercetin cannot be owned. Green tea cannot be owned. No sponsor has a commercial reason to spend tens of millions proving that a compound available for pennies works modestly well, and no regulator is obliged to do it for them. That is a structural feature of how medical evidence gets funded, not a conspiracy, and it produces a predictable blind spot: the cheap and the plausible go unstudied while the patentable gets three trials each.
Meanwhile the viruses keep circulating. Reinfections are common and increasingly subtle, often passing unrecognised. Norovirus is causing outbreaks. Influenza mortality rose this year. Every one of those pathogens runs on the same copier.
Layers, not cures
Physiology rarely turns on a single decisive move. It works in layers.
Vitamin D status. Sleep. Hydration. General fitness. None of these is a shield on its own, and every one of them shifts the odds a little. The zinc and ionophore pairing belongs in that same category: one more layer, most sensibly used in a narrow window, a short course when exposure is suspected or the first symptoms appear, not a daily ritual and not a substitute for anything.
“Everything about physiology and medicine is layers. It’s never this is some kind of miracle cure,” said Dr. Philip McMillan.
That is the right place to leave it. The biology is elegant, the laboratory work is real, and neither of those amounts to knowing what happens inside a person who takes zinc and quercetin at the first scratch of a sore throat. Five years of circulating virus have not produced the study that would settle it, and so a reader is left holding a probability instead of an answer, which is an uncomfortable thing to hold and rather more honest than most of what gets said about supplements.
The experiment has been sitting there since July 2020. It deserves to be finished.
Nebulization of home mixed, sterilized, hydroxychloroquine in home mixed saline nebulization solution is probably the best, longest acting, zinc ionophore.
This application provides near instant maximum benefit of HCQ while using such small amounts of HCQ, with very little of this systemically absorbed, as to eliminate all, or most all, side effects other than a transient bitter taste.
Dr. Zelenko, shortly before his passing, clinically demonstrated nebulization of HCQ for the treatment of people sick with covid (etc). You can make Hydroxychloroquine nebulizer solution at home.
FYI – the historic Zelenko letter “March 23, 2020” “To all medical professionals around the world:”
https://docs.google.com/document/u/0/d/1SesxgaPnpT6OfCYuaFSwXzDK4cDKMbivoALprcVFj48/mobilebasic?usp=gmail&urp=gmail_link&pli=1
Cut to the chase – Hydroxychloroquine administration for most treatment of covid (etc) IS BEST DONE VIA NEBULIZATION for exceptionally rapid effect bringing high levels of HCQ to the target areas with very little systemic absorption hence with very little to no systemic side effects. HCQ pills can also be taken if systemic distribution is also sought.
David E. Scheim, PhD did the gumshoe work working out the details showing doses , amount absorbed , lung tissue concentrations which show that 1 or 2 or so many HCQ pills can be simply converted to HCQ nebulization solution, at home, then nebulized to rapidly achieve the the same lung tissue concentrations as many more pills taken over numbers of days. .
Zelenko’s “Nebu HCQ” c19hcq.org/zelenko.html
“Nebulized Hydroxychloroquine for COVID-19 Treatment: 80x Improvement in Breathing” Vladimir Zelenko M.D – pdf available here https://drelef.org/zelenko/Zelenko-nebulized-hcq.pdf
Nebulized hydroxychloroquine as 150 mg HCQ (my note: amount of hcq in one 200 mg pill) in 6 ml (25 mg/ml) of isotonic sterile solution within the first five (5) days of COVID-19 symptoms (” Nebu HCQ “) has resulted in immediate improvement (<1 hour after use) in breathing in COVID-19 infected patients. Nebu HCQ served as a rescue medication with an 80x improvement in time and efficiency when compared to HCQ tablet (400-600 mg per day) combination therapy or Ivermectin combination therapy. No adverse events were reported outside of a bitter taste that quickly subsided. Average time of clinical improvement of pulmonary compromise precipitated by Covid 19 Covid-19 is primarily spread through the respiratory system and may result in significant pulmonary complications. Left untreated, a subset of patients will progress to acute respiratory distress syndrome (ARDS) and/or pulmonary infarcts. Oral HCQ and Ivermectin combination therapies have proven to be effective prehospital treatments of Covid-19 and its associated complications. However, treatment with oral HCQ may take an average of 80 hours to achieve significant clinical improvement as well as 3-7 days to achieve optimal alveolar concentration of medication. [3] Nebu HCQ administered as microdroplets directly to the lungs achieves optimal alveolar concentration in approximately one (1) hour and is associated with faster clinical improvement, reduction in pulmonary complications and a reduction in medical costs. The clinical data presented in this paper was generated through the routine practice of medicine and is considered "Real World Evidence" according to the 21st Century Cures Act. [4] Innovation Dr. Zelenko notes that ACE2 Technology LLC ("ACE2") developed Nebu HCQ and that Dr…. … …
Nebu HCQ Whitepaper_Scheim.docx https://docs.google.com/document/u/0/d/e/2PACX-1vR_ZkSoL1bJI_Hj75SKoqtjsnGUYC_xCQkIwHvHSoz3y45CBhn8w7BSlsboE1avPw/pub?urp=gmail_link&pli=1
Nebulized hydroxychloroquine plus oral azithromycin for COVID-19 treatment: from days to hours for optimal lung tissue concentrations and viral immobilization
David E. Scheim, PhD
"Abstract
Background. More than 3,300 COVID-19 patients treated at southeast France’s main COVID-19 treatment hospital with hydroxychloroquine (HCQ) and azithromycin (AZ) had a death rate one-sixth the world average. But the unusual pharmacology of HCQ presents a key limitation. Optimal tissue levels can only be accrued with 5-10 days of oral dosage. Thus, HCQ has performed well for early and mixed-stage COVID-19 patients but has exhibited marginal utility in advanced stage cases.
Proposed combination treatment of nebulized HCQ and oral azithromycin. Drug delivery of HCQ through inhalation of nebulized microdroplets will achieve, in hours, lung tissue concentrations equivalent to those accrued over days of oral dosage. Nebulizers are simple, inexpensive and widely available drug delivery devices, and minimal risks of local lung toxicities are indicated for such HCQ drug delivery. Furthermore, HCQ is effective in blunting the damaging effects of pro-inflammatory cytokines in the lungs. The combination treatment of nebulized HCQ along with oral AZ and possibly also ivermectin and zinc could provide a rapid reversal of the progression of COVID-19 both in the respiratory tract and in other body tissues."
This paper has blood plasma HCQ levels from nebulized HCQ "Nebulised Isotonic Hydroxychloroquine Aerosols for Potential Treatment of COVID-19" https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399722/
my "non medical professional" note: imo I expect nebulization of such small amounts of HCQ, as is needed in this application, overcomes virtually all the common adverse event considerations concerning HCQ – probably "check with a covid treating doctor" even the concerns of HCQ use by those with G6PD and without incurring long QT risk in the vulnerable subset of people with HCQ associated risk for long QT. . G6PD link https://my.clevelandclinic.org/health/diseases/22556-g6pd-glucose-6-phosphate-dehydrogenase-deficiency note: Professor Didier Raoult was screening for G6PD and all wore wrist positioned monitors for long QT in his oral HCQ trials with thousands of patients.
An aspect of hydroxychloroquine nebulization not addressed is, with the long 1/2 life of hydroxychloroquine in the tissues, its potential usefulness as a longer acting agent for prevention of or reduction of infection risk.
Note: I bought the Philips Respironics InnoSpire Elegance compressor nebulizer system which is the 100% duty cycle version of the 50% duty cycle jet nebulizer system that Scheim used. No longer available at last check. Any good jet nebulizer compressor nebulizer system with both child and adult size clear plastic masks to enable breathing in through both nose and mouth note: the plug in the wall compressor of a jet nebulizer system is a bit noisy but the better ones put out a high volume and may handle a wider variety of solutions than other types of nebulizers. Perhaps a consideration when converting 1 or 2 or 3 200mg Hydroxychloroquine tablets into a nebulizer solution for immediate effect in the respiratory system vs a week to reach therapeutic levels when using pills with the use of 9.5 times less HCQ then when taking pills and you actually inhale less than 1/4 of solution eliminating most all side effects except a short lived bitter taste.
My "make it at home" takeaway from the references – dissolve, or crush and dissolve, 1 standard 200 mg pill of hydroxychloroquine sulfate (it contains 150mg or 155 mg of pure hydroxychloroquine) in 3 mL of distilled water in a small glass container – if it does not all completely dissolve (fillers in the pill?) it is probably a good practice to use a syringe mounted filter to filter particles that could clog the nebulizer. (or any type of filter such as a paper coffee filter in a pinch). then either (Zelenko) add 3 mL sterile isotonic saline or (Scheim) add 5 mL sterile isotonic saline then place the glass container containing the one jet nebulizer cup's fill worth of solution in boiling water for 10 minutes to sterilize the jar and solution. 1 or 2 or 3 pills is a full course of treatment. ~3 pills worth of solution (and you actually inhale into the lungs less than 1/4 of the HCQ in the solution) reaches the lung concentration almost immediately that it takes 3 pills taken per day for 8 days to finally achieve.
As a conclusion, it is about time to test this in vivo. I think we still have enough RNA Viruses at work, people suffering from it that a relevanz population can created. Animal trials can be made to get a better in vivo indication. But thanks dear Philip to bring this combination to our attention. Keeping Quercetin & Zinkbisglycinate e.g. at home at all times (great shelflife if kept propperly) costs less and can value a lot. Next influenca or respiratory wave ist just around the corner and then we try it out ourselves. Corrupt Pharma will never do! What they might do id rather elaborate on a gain of function version which is Zink-resistant .Could you please mention any of the scarce studies done on Zink and Ionophores like Quercetin? Is Quercetin powder as we take it enough or do we need galenic tricks to increase absorption as otherwise we have enough Serum Zink but too less of ionophore in the serum ?