Covid-19: Chloroquine, Zinc and Quercetin

Chloroquine is a malarial drug first discovered in 1934. It’s still in use for malaria management, although the most common species of malaria-causing organisms are long resistant to it. Hydroxychloroquine (Plaquenil) also has anti-malarial activity, but is much more commonly used to treat certain auto-immune disorders, including rheumatoid arthritis, and systemic lupus erythematosus. Both of these drugs are structurally related to quinine, the famous ‘Jesuit Bark’ (Chinchona spp.) that was the first effective treatment for malaria (and the chemical that gives tonic water its unique flavor). Both pharmaceuticals are long out of patent protection, so generic versions are widely available. Depending on locale, a typical month-long treatment with hydroxychloroquine in the developing world was about US $4.65. Both drugs are on the World Health Organization’s List of Essential Medicines.

All quinine-analog drugs have the potential for side effects. Some are mild (diarrhea, nausea, tinnitus) others can be quite serious (inflammation of the retina, anemia, cardiac instability). Chloroquine and hydroxychloroquine preferentially collect in the lungs, which helps increase potency with smaller doses. However, part of risk is due to the medications also collecting more in cells with melanin, which include skin and eye cells. Damage to the eyes can be a risk with large doses or extended use as a malaria or autoimmune disease treatment. People with cardiac problems may also be more at risk of adverse cardiac reactions. There is also a significant risk of interactions with other medications when taken simultaneously. Because of this, both chloroquine and hydroxychloroquine are available only by prescription.

Chloroquine and hydroxychloroquine have an extensive research basis as antivirals. There are two acknowledged mechanisms by which these drugs exert antiviral effects.

Mechanism I: Endosome Alkalinizer

The process of viral entry involves the transport of the viral genome across host cell membranes, and the subsequent release of the virus genome into the host cell’s body (cytoplasm). Enveloped viruses like SARS-CoV-2 accomplish the delivery of their genomes into the cytoplasm of the host cells by binding to surface molecules on the outer membrane of susceptible cells, and fusing their outer envelopes with host cell membranes.
This leads to the virus being internalized into bubble-like (vesicle) inclusions known as endosomes.

In order to initiate replication, the virus requires that the endosome have a low (acidic) pH. Both drugs are weak bases (alkaline pH) and are rapidly taken up into the endosome, where they raise the pH to a point where viral replication can’t take place.The virus is therefore unable to release its genetic material into the cell and replicate.

Inhibition of viral infection with the increase pH by chloroquine analogs. Steps: 1. Endosome formation; 2. Fusion; 3. Post-translational modification; 4. Uncoating of the virus. ‘X’ marks points in process where chloroquine/ hydroxychloroquine exerts viral blocking effect. (simplified, from Al‐Bari 2017)

Mechanism II: Zinc Transporter

The mineral zinc is involved in many different cellular processes, and has proven crucial for the proper protein folding, the activity of various cellular enzymes, and most genetic transcription factors. In solutions such as water, zinc exists in its ionic form (Zn2+), where two of its electrons are lost to form the Zn2+ ion. This ionic aspect is what makes zinc so interesting from an antiviral perspective.

Ironically, even though zinc performs so many critical functions, the cell is not terribly interested in accumulating high levels of it.

The intracellular concentration of free Zn2+ is maintained at a relatively low level by metallothioneins, small molecules that bind metals like zinc, copper and other heavy metals. The cell aggressively throttles Zn2+ because, at elevated concentrations, it can serve as an intracellular signal molecule, and trigger cell suicide (apoptosis), or even block protein synthesis. If that wasn’t enough discouragement, the cell membrane itself tends to repel zinc ions from binding, in much the same way that two magnets will repel each other when the same poles are brought close together.

Zinc is a decidedly anti-viral mineral. High intracellular concentrations inhibit the replication of RNA type viruses, such as SARS-CoV-2. Zinc does this by blocking RNA-dependent RNA polymerase (RdRp), the core enzyme of their multiprotein replication and transcription complex that is critical for the copying of viral RNA.

That’s the conundrum. In high concentrations, zinc can block coronavirus reproduction, but the cell is typically disinclined to tolerate high levels of zinc due to concerns about its other actions.

Enter the zinc ionophores.

Fortunately, there are molecules that can act as facilitators and enhance the entry of zinc into the cell. These are known as zinc ionophores, and here’s the payoff: in addition to its effects on endosome pH, chloroquine has also been demonstrated to be a zinc ionophore.

But there’s even more to the story. In addition to chloroquine, the nutraceuticals quercetin (bioflavonoid) and epigallocatechin-gallate (green tea polyphenol) are also zinc ionophores. Quercetin plus zinc is being tested as an anti-viral in human clinical trials for the treatment of Covid-19. The combination had already made it through animal trials for use against Ebola and SARS-CoV1, and was approved by the FDA for human clinical trials. Plans are underway for a large scale trial in China for patients with Covid-19.

The anti-parasitic drug ivermectin appears to have ionophore activity, as does the antioxidant resveratol.

How zinc ionophores work. 1. Zinc ions (blue hexagons) are in solution outside the cell. 2. The cell’s membrane and binding molecules limit the ability of zinc to penetrate into the cell cytoplasm via special ports (light green shape). 3. A zinc ionophore (red triangle) activates the port (dark green shape) to allow zinc to enter cell (4). Now in the cell, zinc is then able to block the enzyme RNA-dependent RNA polymerase (black shape), which turns off viral replication.

Getting zinc into the cell is obviously dependent on having adequate levels of zinc outside the cell. With most of us, this is usually not a problem. However, zinc absorption does vary by individual. Physiological stressors, such as infection and inflammation, tend to deplete zinc pretty fast. Fortunately, most of the hospitals that are empirically prescribing chloroquine for active Covid-19 are also supplementing with zinc as well.

53 comments on “Covid-19: Chloroquine, Zinc and Quercetin”

  1. Michael Reply

    Wouldn’t a good amount of daily lemon water leave a nice alkaline ash on the cells and hence make it harder for the virus to replicate?

  2. Barb Healy Reply

    If you already take quercetin (for allergies) will it push zinc into the cells if you don’t have the virus, and is that a good or bad thing?

    • Peter D'Adamo Reply

      Given you have sufficient zinc, maybe. Probably a good thing given events of late.

  3. Sage Reply

    You mention that high levels of ionic zinc in a cell can trigger negative reactions like apoptosis, could taking normal amounts of zinc and zinc ionophores cause that to happen or would you need to take an excessive amount? Trying to understand what the fine line is between a high enough amount to stop the RNA reproduction and low enough to now cause cell death or some other negative impact.

      • Sage Reply

        Haha fair enough. Do you have any idea on volumes to take or is it really on a case by case basis?

        • Sue K Reply

          Most people are saying about 25 mgs of elemental zinc, most are sold at 50 mgs. So probably between the two. You can research these protocols easily online now.

  4. Meyer Stein Reply

    This is the best and most detailed article I’ve come across on the Hydroxychloriquine/Quercetin/Covid-19 connection and really gives explanation and credence as to why Quercetin may be effective at treating or preventing Covid-19. Thanks so much. I don’t know if the Montreal researchers have initiated their trial but we should somehow be testing Quercetin and Zinc here in the US. Is that possible?

  5. RODOLFO E S GOMES Reply

    What about cocaine? How does it affect your blood pH? Out of curiosity you know, I have a friend who has a friend…

    • Peter D'Adamo Reply

      Cocaine is also a vasoconstrictor, so I’m not sure it would work well here.

  6. Jeff Reply

    Hi Dr. D’Adamo,

    Thank you for all the work you’ve done.
    If I may ask, Does baking soda help to alkalize the cells and do you have a recommended amount one should consume?

    • Peter D'Adamo Reply

      I don’t think baking soda will have much of an effect, so I cant supply a dose. However, I’m sure others know more about this than I do.

  7. Sheree Pecoraro Reply

    Wondering if home brewed kombucha would be as useful as the lemon water you commented on above? Or if nothing else, not harmful? I ask because I make it for my husband and son, they enjoy it but obviously I would not want to be causing them harm if they were to catch this virus.

  8. Keith Reply

    I take Warfarin (7 and a half mg’s daily) for a blood clotting disorder, would either Zinc or Chloroquine interfere with that medication. I’m an A + blood group by the way. My mother (a retired nutritionist) loves your work!

    • Peter D'Adamo Reply

      Zinc probably not. Chloroquine interacts with several medicines. I don’t remember seeing Warfarin on the list, but check with your doctor.

  9. Omar Ochoa Reply

    Can you comment on this:

    COVID-19 causes prolonged and progressive hypoxia (starving your body of oxygen) by binding to the heme groups in hemoglobin in your red blood cells. People are simply desaturating (losing o2 in their blood), and that’s what eventually leads to organ failures that kill them, not any form of ARDS or pneumonia. All the damage to the lungs you see in CT scans are from the release of oxidative iron from the hemes, this overwhelms the natural defenses against pulmonary oxidative stress and causes that nice, always-bilateral ground-glass opacity in the lungs. Patients returning for re-hospitalization days or weeks after recovery suffering from apparent delayed post-hypoxic leukoencephalopathy strengthen the notion COVID-19 patients are suffering from hypoxia despite no signs of respiratory ‘tire out’ or fatigue.

    • Peter D'Adamo Reply

      Maybe. RBC don’t have nucleus or protein synthetic machinery, so I wonder exactly why a virus would be interested in trying to get into one, since there is nothing for it to use to reproduce itself.

      • Jon Scott Reply

        Sialic acid present on RBCs so maybe an unintentional ‘own goal’? The virus is credited with intelligence but it is just an evolutionary ‘thing’. From what I can tell, C19 does not use Sialic acid but Sars CoV does. I’m yet to be persuaded it does not although it seems to be well accepted that it uses ACE2 as a receptor.

        • Peter D'Adamo Reply

          1.) Appologies if my facetiousness might have escaped you.
          2.) Would need gene to code for neuramididase.

  10. Heidi Reply

    Quercetin plus zinc: I believe in this. I’ve been eating black soybeans which are super high in quercetin (the skins) and also zinc.

  11. Heidi Reply

    I understand this pneumonia is more like high altitude sickness. We take chlorophyll before climbing really high elevations to avoid altitude sickness. Any benefit to taking this?

    • Peter D'Adamo Reply

      Possibly, although Chinchona Bark will have variations in quinine content which makes dosing difficult.

      • Mae Flick Reply

        Could you figure out the dose… ❤️
        Many thanks. Just ordered lots of Cinconcha Bark at 682 mg per .7ml.
        If they won’t give us HCQ… we will find other ways… Thank you for all of your hard work!

  12. Mary Ann moss Reply

    Thank You It was great to hear your take and input in this situation.

  13. Gamel Appiedu Reply

    Dear Dr. D’Adamo…..I have read your books, the information of which works for me staying healthy. This is the first time I have read an explanation to the chloroquine and hydroxychloroquine, zinc connection to stopping Covid-19. Thank you very much for your work. I am employed in Saudi Arabia and would like to communicate with you sir. Thank you.

  14. GeVanK Reply

    Dear doctor, what is your opinion on Dr. Andrew Kaufman’s research on COVID-19 being an EXOSOME and NOT a virus?

  15. Maureen Ellis Crean Reply

    Hi Dr. D’Adamo, I am a great believer in your work, 22yrs ago my husband James suffered from chronic chrons disease, our family doctor and numerous consultants put James on a lot of medication, he was never taken off one type of meds to replace another the doctors continued to give him more& more medication it was ridiculous. His symptoms increased and he was in constant pain he also had crippling bouts of diarrhoea. We went to Killarney, Co. Kerry with our 3 kids on a holiday and I read an article on Dr. D’Adamo, I found it so interesting I bought the book Eat right for your blood type James is blood group is B, he was eating all the wrong foods for his blood type. With the help of our local health shop owner Mary Widel, we weaned him off all meds and put him on blood B type diet Including supplements. One yr later he went to see a renowned consultant (we had been waiting 2yrs for app) in Cork . The consultant could not believe how healthy my husband was and was also shocked that he was off all meds. The consultant took notes on James diet etc and told him the disease would probably come bk ……James Has been free from chrons since ,thank god for you DrD’Admo, you are amazing may the lord fasten the life in you and keep you safe and well always. Maureen

    • Dr. Grouf Reply

      Hydroxychloroquin is commonly prescribe to treat autoimmune conditions. Isn’t it true that covid mortality is linked to cytokine storm which is an autoimmune response. Would not hcq mitigate that to prevent mortality numbers, given its traditional use as well?

    • Catherine Shortt Reply

      I love that phrase, May the lord fasten the life in you! Is that common in your area?

  16. Taha Reply

    Thanks Doc. This is brilliant. I have one question: Can HCQ be used together with Quercetin considering both are Zinc Ionophore?

  17. Rebecca De La Fuente Reply

    How about using Artemisia Annua (Sweet Wormwood) a natural Quinine in place of the Hydroxychloroquine which must be prescribed? I read it is the basis for Madagascar’s COVID Organic tonic and also that it is used to treat drug resistant malaria. I have used it with Zinc on viral positive people and it decreased symptoms in 24 hours with no symptoms other than mild fatigue in 48 hours.

  18. Tass Nidis Reply

    Greetings Dr. D’Adamo,
    If one was diagnosed with Corona Virus and much preferred to self isolate AND self help rather than hospitalisation and also believed in the Quercetin/Zinc protocol, what would you recommend as the dosage and frequency of the above supplements ?

  19. Laura Reply

    Wow. I am an A- blood type and I had COVID from late March to middle April. First symptom (flashes of minor fever and an acute sore throat) made me rush for my usual fix: ginger honey lemon tea. One litre or so a day when I have a cold is usually enough to put symptoms at bay but not this time. It took 4 litres a day for me to feel good. So I kept at it. A doctor said to consider zinc and I add it (one a day). There were some rough days around day 17-21 (weird breathing & tachycardia) but after Five or so days of eating only beneficials I started feeling better. It was March nobody knew what was good so now I am grateful that i was lucky to do the right thing.

  20. Laura Poirier Reply

    Hello Dr…. I am also interested in the dosage recommendation and length of time to take quercetin and zinc together. I pretty much feel like I had covid-19 last 3 weeks I did quercetin and zinc, little colloidal silver vitamin b my usual D and Co q10 but is quercetin and zinc to be taken together at the same time?

    Thank you!

  21. Johnna Ballard Reply

    I am certain I had COVID in late January. I have been taking your Glycosia supplement for over two years now, which has resveratrol and quercetin. I never get sick, but caught a severe upper respiratory illness my best friend caught. I had shared food/drink with her, so I knew I was going to get it. It was all chest congestion and extreme, debilitating fatigue. I kicked it in under 48 hours and it was one day of feeling like death. My friend suffered much worse and her symptoms lingered for three weeks. She tested negative for the flu and was diagnosed with an upper respiratory infection.

    I will be a customer for life as I believe your supplement helped my immune system fight off this illness. I am also blood type A. I researched scholarly journals on quercetin a few months ago when I made the connection. It is promising.

    Thank you.

  22. Rebecca Denny Reply

    Great article, very well done!
    I’ve been taking Quercetin, Zinc, NAC (protects the lining of the lungs), and vitamins C,D,E,K as well as Selenium and Magnesium since March.
    I also drink about 24oz of Aqualiv (brand) filtered alkaline structured (high oxygenated) water every day.

    I’m not a doctor, I am an herbalist focusing on natural methods of healing for my family. I went to work in February searching for the mechanism of how the virus works, and then found the natural herbal and supplement components that would counter the function of the virus. What I listed above is what I settled on to take for myself and for my family.
    I don’t pay attention to social distancing, I don’t wear a mask, and as far as I’m aware I don’t have “The Rona.”

  23. Robin Rothstein Reply

    Hello Dr. D’Adamo-
    Great article!
    I too would like to have some sort of recipe to have at home just in case either my husband or I start showing symptoms. ie: how many mg’s Zinc (and in what form?), how much quercetin (or Artimisin to be effective with the zinc?
    Thank you!

    • Joe Milligan Reply

      The recommended dosage is 500 mg quercetin 2 x a day and 500mg zinc once a day. Take the zinc with 1 of the quercetin at night. I got this from watching many videos on this approach. I am not a Dr

  24. chris m mcwilliams Reply

    Excellent article. What are your opinions on commonly-cited research that higher doses of zinc can actually suppress the immune system? Therefor somewhat of a double-edged sword in treatment.

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