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Chloroquine, Past and Present

Now that chloroquine is in the news everywhere, I thought it might be interesting to have a closer look at the compound. The first part of this post will be chemistry-heavy, further down we’ll get into the pharmacology and medical uses.

Chloroquine’s fame is as an antimalarial drug, and the history of antimalarials starts of course with quinine (at right). That’s the active compound in cinchona bark, whose medicinal properties had long been known among the natives of South America in the tropical parts of the Andes – the Incas and the people(s) that the Incas absorbed into their empire. It doesn’t seem to have been used by them as a malaria treatment per se, but rather was known as a treatment for shivering, brought on by either low temperatures or by malaria itself. The Spanish conquerors introduced it into Europe in the 1600s. The study of cinchona bark and its extracts is a key part of the history of medicinal chemistry as a science – the pure compound was extracted in 1820 by Caventou and Pelletier, and the development of Perkin’s mauve was an attempt by Perkin himself to synthesize quinine. From a chemical standpoint, that work was doomed – no way, no how, was he going to make quinine – but the purple dye he did produce made him wealthy, famous, and kick-started the synthetic dyestuffs industry and industrial organic chemistry in general. Quinine itself wasn’t synthesized until 1944, a wartime effort by Woodward and von Doering, and there has never been a synthesis that can compete with extraction from the bark.

The search for quinine alternatives started off early, not least because the natural product itself was first a monopoly of the Spanish crown and later (via horticultural espionage similar to what happened with rubber production), a market sewn up by the Dutch through plantations in Indonesia. In 1891, Paul Ehrlich himself found that methylene blue (at right, synthetic dyestuffs, showing their stuff) was actually an antimalarial compound, although it wasn’t really effective enough to take over from quinine itself. Besides, at the doses needed, it tended to turn people (or at least various parts of them) blue. This is what you get when you start a pharmaceutical industry out of a pigments-and-dyes one. As another example, the first sulfa drug, Prontosil, tended to permanently turn people red; it was only later discovered that the red dye part was just structural baggage and all the activity was in the little sulfonamide on the side.

One of Bayer’s students, Wilhelm Röhl, was working at Bayer and started a program to test the company’s synthetic compounds for malarial activity and to make analogs around the active ones. That led in 1931 to quinacrine (at right), also known as mepacrine or by its old trade name of Atabrine. You can see the methylene blue roots in its structure, although this one isn’t blue, it’s yellow, and also had a noticeable patient-staining effect.  It’s quite effective as an antimalarial and was used in huge quantities during the Second World War, but it has serious side effects. Not only will it turn you yellow, it can lead to psychological effects (depression and psychosis), seizures, permanent tinnitus and balance problems, and more. Other newer antimalarials such as mefloquine (Lariam) have the same problems.

And so does chloroquine, at right. That one was synthesized in 1934 by Hans Andersag at Bayer, and the initial evaluation of the drug by Bayer marked it down as too toxic for human use. This was later considered a major mistake (the “resochin error”, using the drug’s German trade name), as it became a major antimalarial drug after World War II. It was considered a major advance in that it had strong antimalarial activity and didn’t actually make people change into various rainbow colors. You can see how this one came from quinacrine, just chopping off that third ring, which also gets rid of the colorful visible-light absorption properties. And it’s also getting back a bit closer to quinine, as a substituted quinoline with aminoalkyl group up at the 4 position. But it still can lead to depression and other effects. Hydroxychloroquine came along in the 1950s, and just has an extra OH group coming off of one of those N-ethyls over at the end of the chain; it’s quite similar to chloroquine itself.

You might wonder how an antiparasitical drug might do that, but the problem is that the mode of action of all these drugs against malaria parasites is still being argued over. And there are almost certainly several modes of action at work, which will go on to have different effects in different human tissues, etc. Both chloroquine and hydroxychloroquine are used off-label for rheumatoid arthritis and for lupus, but how they work in these areas is another shoulder-shrugger, and there are side effects in the eye. It’s been suggested as an adjunct in some cancer therapy regimes, but there are problems there, too, in the kidney.

So if you see someone confidently explaining just how chloroquine exerts whatever antiviral activity it may have, feel free to go read something else. No one’s sure yet. Viruses certainly have fewer moving parts than plasmodia do, so it might be easier to figure out what’s going on, but anyone who’s done “target ID” will tell you to settle in for some work. There are all sorts of suggestions, some of which are recycled from antimalarial hypotheses. One that I find particularly amusing, for personal reasons, is the idea of complexing zinc ions. I say that because over 20 years ago, I was on a project targeting a particular phosphatase enzyme (I know, I know, it was as doomed as all the other phosphatase work from that era. . .) Our lead compound was pretty similar to chloroquine, which is interesting because I was working for Bayer at the time – there were still plenty of such structures from way back in the compound collection. Unfortunately, none of the analogs we made were active in the slightest, so I did what I should have done right at the start and ordered up some of the original powder sample for more stringent analysis. Sending it out for elemental analysis and checking all the metallic-element boxes revealed that it was about 40% zinc by weight, and a zinc-free sample was, you guessed it, about as active as corn starch. So yeah, I can at least believe that these things complex zinc, for what that’s worth.

And so to today. As I said yesterday, I find the reports of chloroquine/hydroxychloroquine activity against the coronovirus very interesting, but preliminary. There has as yet been no well-controlled trial, and unfortunately the effects seen are still the sort of thing that can look exciting but disappear when you look closely. I mean that. It happens all the time – ask anyone else who does drug research for a living. If this drug isn’t useful, then sending hundreds of millions of people out to swallow all of it that they can find will be a massive waste of time and money, and will actively harm people besides. This is not a benign compound; it should only be taken when you have a solid expectation of benefit, and (saying it again), we don’t yet have that. Better trials are cranking up right now: please, wait for those. The generic drug companies (Teva and Mylan, I’ve seen so far, and there’s this) that are cranking up production are doing the prudent thing – if this reads out well, we’ll need a lot of it. But we’ll need to give it to people who are in bad shape from the viral infection, too, remember that, and I fear that a lot of people around the world are just starting to take it now in hopes of a prophylactic effect, which is (saying it again) a bad idea.


215 comments on “Chloroquine, Past and Present”

  1. KS says:

    Chloroquine and hydroxychloroquine do have pretty significant adverse effects at high doses. Which make sense, since these compounds accumulate in the lysosomes, due to their high logP and basicity.

    1. cirby says:

      The comments I’ve seen on adverse effects from hydroxychloroquine are supposed to be from very high doses or from long term accumulation – one of the doctors who posted pointed out that the eye problems caused only happen after twenty years or so of constant dosing, and most of the other side effects are supposedly in the multiple-year range, not the couple of weeks of moderate doses we’ve been hearing about for this use.

      1. Robert says:

        EXACTLY. The side effects are modest for most, especially on a 10 days or less regimen.
        Approx. 5% or higher risk of NOT taking it when ill from coronavirus it is you could end up in ICU on a ventilator, on the other hand, the risk of taking it and getting serious side effects is minimal at about 1.5% in the study below.

        Google this title:
        Reported Side Effects to Chloroquine, Chloroquine
        plus Proguanil, and Mefloquine as Chemoprophylaxis
        against Malaria in Danish Travelers

        85% of Danish travelers reported no side effects

        minor side effects are:

        stomach pain (take only with a full meal)

        the depression / anxiety incident was ONE person – – we don’t base science on what happen to ONE person.

        severe side effects in only 1.5% of cases

        Only LONG TERM USE for many months or years can have retina involvement.

        1. John says:

          To fully understand this experiment though you would need to track down the original scientific article and read it in its entirety. The evidence you cite would have come from a single study, and just like you said you cannot generalize based on the data taken from a single test subject, you cannot generalize your conclusion to the entire world population based on a single scientific study.

      2. Toni says:

        I’d be more careful. 500mg twice daily over a week is a lot.
        Many of the PK and Tox studies from the 80s show that high doses (> 5mg/kg) can lead to severe side effects beyond retinopathy even with short-term administration.
        But in general, chloroquine can be considered safe, at least for standard malaria therapy.
        I might be a bit more concerned about the combination of chloroquine plus azithromycins for certain patients, as both drugs may lead to QT prolongation.

        1. RobK says:

          the dose of chloroquine base is 300mg bid. the dose of chloroquine phosphate is 500mg bid.

        2. Chris Pachell says:

          The Ordoñez family of Cuenca Ecuador became immensely wealthy near the end of the nineteenth century from quinina exports to Europe. Hortensia Mata de Ordóñez became a great philanthropist in her time and save many from malaria around the world, specially in Europe.

        3. jemila says:

          500 mg twice daily sounds like a possibly fatal overdose. The report I read said dosage is 500 mg once a week, and a fatal dose is only 5 times that. Plus it bioaccumulates, has a long half-life in your body. Also, it is a bodyweight-sensitive dose, so if you are a small person, take a smaller dose.

          1. Brian says:

            Would malerone theoretically would that same as chloroquine with zinc on Corona?

          2. John says:


            This source indicates that rheumatoid arthritis patients are prescribed several hundreds of mg of hydroxychloroquine daily.

      3. Harry Berry says:

        Thank you.

    2. Personal experience (family member) of the life-threatening and long-term effects of very high level chloroquine overdose (respiratory failure, brain injury and permanent neurological/motor impairment), with Parkinson’s-like features during convalescence. Thankfully, overdose at the same high level is a very rare occurrence.

      1. Maya says:

        Anything taken too much can cause problems

    3. Dylan says:

      I obtained hydroxychloroquine for my mother who was deathly ill with covid 19 for 14 days straight her overall health was gradually declining and doctors would do nothing so I proceeded to take action after she administered hydroxychloroquine compounded with azithramiacin she became even worse complaining of severe diarrhea and vomiting and coughing up massive loads of phlegm, however I assured her this was a good thing. By day three of the treatment she claimed to feel like a new person! This treatment is in fact violent to the body. However this treatment is absolutely effective in fighting this virus and desease

      1. Jorge Romero says:

        What are the quantity given to your mother?

    4. BLStein says:

      I am a retired 25 year US Navy Corpsman. The Navy routinely used chloroquine as a chemoprophylaxis against malaria in the 70’s. Hundreds of thousands of doses given with extremely low serious reactions to a young healthy population. Most common complaint was mild diarrhea. Would be interesting to look at those records.

    5. Judy Clark says:

      What are your thoughts on quinine and zinc as a cellular boost?

  2. Barry says:

    Great write-up on a dubious therapy.
    People are gearing up favipiravir too, on similarly preliminary signs. But favipiravir is known to be teratogenic and to whack red-cell production. It also should not be handed out w/o good cause.

  3. Cristiano de Carvalho Leão says:

    If effective, is there any chance the indiscriminate use to cause the surge of a COVID-19 Chloroquine resistant strain?

  4. Michael J Olson says:

    “While the media is focused on the vaccine race and leaving the discussion of THERAPEUTICS almost completely neglected, a recent well controlled clinical study conducted by Didier Raoult​ M.D/Ph.D, et. al in France showed that 100% of patients that received a combination of HCQ and Azithromycin tested negative and were virologically cured within 6 days of treatment.”

    1. Derek Lowe says:

      See yesterday’s post. That trial was very small and not really “well-controlled”. It does, however, immediately suggest that a larger and stricter trial be run.

      1. adam zweifach says:

        Everyone’s talking about chloroquine, but it wasn’t really very effective on its own. It was the combination of chloroquine and azithromycin that appeared to be effective.

        Any thoughts on why that might be? Looking at pubchem, azithromycin does quite a lot of things in quite a lot of systems.

        These results merit further testing. I would think it would be evident fairly quickly if there was something significant there.

        1. Derek Lowe says:

          Agreed, the effect size looked large enough in the small trial that if it’s real we should see a good signal. Azithromycin’s pleotropic effects seem to be a lot more wide-ranging than I’d realized!

          1. adam zweifach says:

            I saw a table of the data
            The data are spectacularly iffy. It looks like there were a total of 6 patients in the chloroquine. azithromycin treatment group.

            Definitely enough to want to do a real study, not enough for the president of the united states to tout from the bully pulpit. I can see wanting to give people hope, but there’s a right way and a wrong way to do that.

          2. Andy II says:

            I assume that someone has already pointed out but just in case.

            People are still looking into a significant role of a secondary bacterial infections in a virus infection.
            It is therefore very important to include antibacterial drug for lung infections (such as azithromycin) in the treatment.

            Bacterial pneumonia was main killer in 1918 flu pandemic (

          3. Derek Lowe says:

            Reports earlier were that bacterial pneumonia was (oddly) not a common sequel of the viral infection in China. Let’s hope so!

          4. Andy II says:

            Following up my previous comment.

            “Secondary bacterial pneumonia can occur from numerous pathogens (eg, Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae). The most dreaded complication is staphylococcal pneumonia, which develops 2-3 days after the initial presentation of viral pneumonia.” (

            MRSA is a drug-resistant Staph aureus. Rate of MRSA is very high in Italy. Azithromycin is not effective against MRSA and H influenzae. we may need MRSA active pneumonia drug (Zyvox?)

        2. Chuck Briggs says:

          Then, u might want to get on your knees now & begin praying to ur God(s) that chloroquine indeed works with few/manageable side-effects.
          We will either win under Trump or lose under Trump.
          Love it or hate it but it is what it is.

          1. Twizzler says:

            Please clarify. It seems to me that those are indeed the possible outcomes. To be fair, I suppose it could be undecided at the time Trump leaves office.

        3. Maureen says:

          What everybody should be talking about is the HCQ trifecta, which also includes zinc. Zinc is the key to supporting the immune system. HCQ is key to putting the zinc in the cell where the virus is.

  5. Alia says:

    In Poland, chloroquine has been officially approved for use in COVID-19 and our generic drug company Adamed has promised to ramp up production. Chloroquine has also disappeared from pharmacies, although it’s not really clear whether it was the government seizing the reserves to distribute to hospitals or people asking their friendly docs for a prescription “just in case”.

    1. Mr. Joshua says:

      This is NOT TRUE, people are dying trying this without a doctor. Please post ONLY FACTS!!

      1. Jon Con says:

        People are dying from taking fish tank cleaner a name similar to the drug. The headline from CNN was inaccurate.

        1. Derek Lowe says:

          The “fish tank cleaner” is the exact same compound. A lot of people are confused on this. It hasn’t been formulated for human dosage, of course, and it isn’t held to the same manufacturing standards. But it is chloroquine phosphate, which is the exact same compound being used in some human virus trials as we speak. It’s not some sort of bleach, which is what “fish tank cleaner” makes people imagine.

          1. Kari Pollock says:

            A typical bottle of fish tank cleaner, even if it was the same without any other toxic substances, is 20 times the recommended 500 mg chloroquine phosphate per dose. If the couple split and drank one bottle, they were still getting a 10x dose, before even thinking about other substances.

          2. Derek Lowe says:

            I can well believe it. And one of the problems with hydroxychlorquine is a rather low therapeutic window when you start to go to these high doses. From my scan of the toxicology literature, a 2 gram dose in a healthy adult is almost always tolerated, while a 4 gram dose often leads to death.

        2. Tony Ruggia says:

          With respect, but why would someone take fishtank cleaner? This is their stupidity if they then suffer from it. And no, this is not the same as the medication. So why are people exaggerating and manipulating facts

          1. Megan H says:

            Ha! Darwinism at its finest.. truly naturally occurring Darwinism amidst a forced Darwinism. Quite a conundrum. Either way, population control was the desired effect of “accidental breach” of an engineered virus, and appears it will be the outcome regardless!

            I can hear my father now, 🗣
            “READ THE DIRECTIONS!!”

          2. Tee says:

            It was murder on her behalf. Plain and simple.

  6. Alex A says:

    We knew in 2006 that chloroquine treats newborn mice infected with SARS-coronavirus when their mothers are given maximum ‘safe’ doses of chloroquine, and pass it through their breast milk. We knew in 2006 that hydroxychloroquine treats lung cells infected with SARS-coronavirus.

    1. jim says:

      official publication by Dr. Fauci’s in Virology Journal on August 22 , 2005 search this and see what he said about it. He gives high praises on both of those products.

  7. Mad Chemist says:

    As a non-med chemist, what I’m trying to figure out is why chloroquine got tested in the first place. Was this a case of throwing everything at the wall and hoping something sticks, or is there some history with antimalarials and viruses that made it an interesting test case?

    1. Xmas says:

      People in here may know better, but chloroquine was known as an antiviral and, I believe, is used as an HIV treatment.

    2. Philip says:

      I guess it was a drug repurposing strategy using FDA approved drugs that revealed chloroquine and many others. Your “throwing everything at the wall” analogy suffices.

    3. milkshake says:

      Chloroquine screws up endosomes, and that plasmodium parasite as it cannot stash away excess of iron left after gobbling up all that hemoglobin. Endosomes also happen to play key role in the virus particles getting into cell – internalizing that receptor-bound virus. Biologists who develop transfection vectors, even nonviral one, often use chloroquine to look at the mechanism of the nucleic acid getting inside the cell and being released from the endosomes. The immunosuppressive effects of chloroquine are probably of the same origin

    4. Dale says:

      This report in China (using hydroxychloroquine in treatment) was considered due to it’s ‘immunomodulatory effect’ for treatment in critically ill SARS-CoV-2 infected patients.

    5. Thomas says:

      Excellent question. When you are a biologist interested in a new screen, new biology etc – you often start screening a collection of existing drugs (some companies sell plates with all approved drugs). This way any hit will already have lots of data attached to it (PK, safety, pharmacology etc). I believe the activity of Chloroquine against COV-19 was found this way (see High-Throughput Screening and Identification of Potent Broad-Spectrum Inhibitors of Coronaviruses
      Liang Shen, Junwei Niu, Chunhua Wang, Baoying Huang, Wenling Wang, Na Zhu, Yao Deng, Huijuan Wang, Fei Ye, Shan Cen, Wenjie Tan
      Journal of Virology May 2019, 93 (12) e00023-19; DOI: 10.1128/JVI.00023-19) from May 2019

    6. Big B says:

      ‘The first place’ is years ago. We’ve been battling coronaviruses for a long time. There are SARS, MERS, feline and porcine coronaviruses and several that cause the common cold. There have been in vitro, in vivo and clinical trials using chlorine for a long time. Take a look at this review for some background

    7. Chester says:

      I read an article, a few weeks ago, about a doctor, in 2003, who was researching the effect of Chloroquine on the Sars virus.

      He had excellent results, but before they could do larger studies the SARS virus epidemic ended, and his research was put on the back burner, replaced by something more urgent.

      After SARS-2-Covid started spreading, he remembered his research from 2003 and went public.

      It seems the idea for Choroquine, as a possible cure, came from his research 13 years ago.

    8. Jose D Ortiz III says:

      It was largely this paper :

    9. Rajesh Pandya says:

      Hypotheis – reasoning

      1. Corona virus in RNA type and replicates with Trancription
      2. Transcription requires Amonoacids and specfic codons ( triplets) nucleotide for example AUG always initiates Transcription and Tremination codons terminate Transcription,
      3. Intitiating codon has affinity to Hydroxyl group and terminating codons have affinity to phosphate group.
      The phosphate moeity in chloroquin phosphate attaches to terminating codons and increase number of terminating codons, thus incducing termination of transcription, I do not have practial experiment on this and does not have data to prove this , However this is most reasonable explanation.

      1. Anonymous says:

        Rajesh Pandya, “The phosphate moeity in chloroquin phosphate attaches to terminating codons”: Chloroquine phosphate (or diphosphate) is the phosphate salt of chloroquine. Think sodium chloride = Na+ … Cl- . A nitrogen in chloroquine (C) is protonated to CH+ and the phosphate anion H2PO4- is the (inorganic) counterion. The cellular concentration of phosphate is already pretty high and there are already many phosphate dependent pathways at work, including transcription. I don’t think a smidgen more of phosphate, delivered as this salt, is going to be the key.

        I think the effect is more likely due to the organic part, the chloroquine part, of the salt.

        1. Gus says:

          MedCram Presentation on this….

  8. Tom says:

    On some of those early anti-malarials that caused permanent staining (or not) I wondered what the treated patients looked like under ultraviolet light!

  9. RandomPharmacist says:

    Thank you very much for posts Derek, with the amount of disinformation that’s walking around these weeks we need you more than ever!

  10. Gambler says:

    One minor quibble – malaria and trypanosomes are quite distinct parasites. Chloroquine target Plasmodium species, the causal agent of malaria. Anti-trypanosomals (including ethidium bromide and arsenicals) are another interesting set of compounds with non-benign toxicity profiles. Trypanosomes cause African sleeping sickness and Chagas disease.

    1. philip alabi says:

      Yes. You’re right.

    2. Derek Lowe says:

      Fixed, thanks!

  11. In Vivo Veritas says:

    Jeez, I feel like, as an in vivo guy, I knew this already. I have been instinctively self-dosing with quinine mixed with an organic solvent supplemented with a naturally occurring source of vitamin C. I had been doing this prophylactically before Covid-19, but now, in the face of WFH, I’ve moved up my daily regimen to coincide with my 3PM meeting.

    1. old man sitting next to me says:


    2. Mark Hahn says:

      Don’t forget the Juniperus communis…

    3. Jag says:

      Yes, time for another G&T

      1. aairfccha says:

        Back to the roots… making quinine palatable was the reason for inventing the G&T in the first place.

  12. Wilhelm C says:

    Here is an interesting overview of treatment logic from ArsTechnica

  13. What about Thymoquinone?

    It and other plant extracts are supposedly effective against mouse coronavirus:

    The effects of Nigella sativa (Ns), Anthemis hyalina (Ah) and Citrus sinensis (Cs) extracts on the replication of coronavirus and the expression of TRP genes family

    1. Buddy Rakhmadi says:

      Is it true that Hydroxychloroquine, is a derivative of thymoquinone (TQ)?

      1. KazooChemist says:

        No. They have very different structures. Google the names and compare.

      2. Derek Lowe says:

        Not at all – completely different structures.

        1. Beenish says:

          What does below mean please

          Synthesis of Thymoquinone derivatives, that is bromoalkyl-2,3-dimethyl-1,4-benzoquinone was performed by two sequential routes, that is oxidation of hydroquinone and alkylation of benzoquinone in mild conditio

        2. maria says:

          “It can be noted that a number of bioactive components [of Thymoquinone] such as nigellimine share structural similarities with chloroquine and hydroxychloroquine.”

    2. Salha says:

      Hi it is amazing ! Thanks for sharing this paper . It seems to be published in 2004. Is there any research currently going on related to thymoquine & novel corona virus ?

  14. I prescribe Plaquenil extensively in patients with autoimmune conditions.The safety profile of this drug is excellent. It is also still used for malaria prophylaxis in healthy individuals .it is not a new drug. I don’t see the reason of labeling it as dangerous. The question is : does it work for Covid19 prevention and treatment? The answer is “the current limited evidence suggests that it does”. What i can tell you that I am aware of a number of doctors in the US who are currently infected or waiting for results who are taking the drug. And I cannot blame them.

    1. Cindy says:

      Are you saying that generic Malarone is a potential treatment for COVID-19? Do you have any research that I can read? And do you have an idea what the dosages would be?

  15. Giannis Zaxarioudakis says:

    Chloroquine has shown a clear in vivo result in laboratory animal for other coronaviruses.

  16. R.Vairavan says:

    Viruses can’t be countered by virucidal drugs. Hence I don’t believe in antiviral drugs. Viruses need cellular receptors to gain an entry into the cell. Hence we have to deform the configuration of the cellular receptors. What are the major receptors?. ACE2 and COX2 which gives entry to the viruses. Chloroquine alters the glycosylation of the ACE2 receptors and hence may be useful. Nimesulide may be useful against COX2 receptors. These two drugs are anti-inflammatory drugs, which alter receptors and would prevent virus entry into the cell. I don’t believe in vaccine, plasma, monoclonal antibody and antiviral drugs

    1. Brian M says:

      What about the protease inhibitor camostat mesilate which has shown in studies to have a 1000 fold reduction of viruses that attach to TMPRSS2 on lung cells….

      1. Martha Whitehill says:

        TMPRSS2 cell line – look at CATB/L -***blockade of both***cysteine proteases – cathepsin B and cathepsin L – are necessary

        New IV drug impacting TMPRSS2:

        Do you know ACE2 normally binds to a tryptophan transporter – BOAT1 (the O is “raised”) ? It is responsible for tryptophan absorption in the bowel (= IBD). And sodium channels are involved via renal Prostasin.

        Odd question, but what about ammonium chloride? (Smelling salts)- blocks CatB/L activity Protasin and cystic fibrosis. Goal looks to be to block sodium channels.

        Furin-mediated cleavage of α-ENaC activates ENaC . See Furin’s job in initial link.

        Red tide toxin, brevetoxin (= coughing on the beach) also impacts sodium channels – big time.

    2. drsnowboard says:

      you don’t believe in directly acting antivirals? How very scientific.
      Like the anti HIV cocktails, the anti HCV triple therapies etc? Inhibition of viral replication is a proven tactic, reduction of viral load which allows the host immune system to clear the virus .
      Read more.

  17. Salutations Mr Lowe!
    I would like to thank you for being the informative voice of reason in those troubled times. I would also like to know your opinion, and all the facts you can give us, on quercetin. It is currently in our local news here in Quebec since a research group (Dr. Michel Chrétien’s team at the Clinical Research Institute of Montreal) has sent a batch to be tested in China. I have put the link to the news story in the website field.

    All I know about quercetin is, that for me anyway, it works better than antihistamines to suppress the symptoms of my pollens allergies, but it requires frequent and massive dose to works against allergy, probably because it has a poor bioavailability.

    Again, many thanks for your blog, you are a darn good writer!
    p.s. Sorry if my writing is dubious, English is my second language

    1. Derek Lowe says:

      I’ll have a look! Quercetin doesn’t have a particularly good reputation in the drug screening labs, is the only thing that I can say right off. It tends to hit a lot of proteins, so you can find all sorts of activities if you look for them. That said, the data will tell the story. . .

      1. Robert says:

        Quercetin has miserable solubility in aqueous systems, less than 1 mg. per liter.

        1. Ed Dwulet says:

          take a look at enzymatically modified isoquercitin

        1. Ed Dwulet says:

          A challenge to the explanation of quercetin bioactivity was represented, until recently, by the contradiction between its extremely low plasma concentration after oral administration and the demonstrable systemic effects.

          1. Ed Dwulet says:

            quercetin also had antiviral activity against HIV-luc/SARS


      2. Vonda Stuart says:

        Quercetin used with bromelain and vit-C is more bioavailable.

      3. George Stanchev says:

        Here is something interesting article regarding Quercetin:

        Apparently this doctor with a lot of street cred (at one point the 6th most cited scientist in the world) in Montreal is starting clinical trials of Quercetin. Already raised 1m. Past work from the SARS epidemic.

        Also, quercetin was screened as one of the top 5-6 for having high affinity to the S-protein:

        This is in vivo from SARS times (2004):

        “Assays with the HIV-luc/SARS pseudotyped virus showed that quercetin also had antiviral activity against HIV-luc/SARS, with an EC50 of 83.4 μM (Fig. 3). The cytotoxicity of quercetin was very low, with a CC50 of 3.32 mM (data not shown). As an FDA-approved drug ingredient, quercetin offers great promise as a potential drug in the clinical treatment of SARS.”

      4. Mel Fitz says:

        Interestingly, the computer model run on the IBM Summit supercomputer by The University of Tennessee, Knoxville & Oak Ridge National Laboratory analyzed about 8000 compounds against SARS-CoV-2, and quercetin was one of the top compounds identified as a potential therapeutic.
        The full scorecard can be downloaded here:

  18. Dorothy M says:

    I thought chloroquine’s main action is to alkalize endosome/lysosmes so prevents access to cytosol. That is why it works in cells in vitro. From what I have read it is not very effective against viruses in vivo. That should have been pretty straightforward to show and so the lack of data that it is a good anti viral indicates that it is not- don’t you think?

  19. Guy Crouchback says:

    By way of distraction, dark humourists might appreciate the motivational sign posted at the US Army 363rd Station Hospital on Papua, New Guinea, during World War II, which features in the Atabrine Wikipedia entry:

    In similar vein, US agents in the Sino-American Cooperative Organisation (SACO) serving in China and Mongolia reputedly “…even took Atabrine tablets to yellow their skin. They didn’t expect to fool anyone face to face, but the disguises helped them blend into the landscape.”

    The past is another country, they do things differently there.

    1. rtah100 says:

      Major Crouchback, bring me more medicinal whisky!

      1. Guy Crouchback says:

        My pleasure, Apthorp old chap. Better watch out supplying you with medicinal snifters on the side doesn’t blot my copybook again. Must honour the old sword at all cost, mustn’t we? Pity old Ritchie-Hook blew himself up last time round on that last spot of biffing. Would have had a whale of a time this show rounding up errant civilians. Good to see that Capt Corante fellow doing a wizard job, a true Officer and Gentleman. No higher praise to a yankee from a mere limey than that.

        Men and Women at Arms – Unconditional Surrender not an option.

  20. Dr. Saysno says:

    On the topic of quercetin, have people tried curcumin?

    1. Ed Dwulet says:

      Curcumin will raise serum zinc levels — zinc plus curcumin plus quercetin may mimic the action cholorquine in fighting COVID-19

      1. DrOcto says:

        Are you sure you don’t want to add some silver colloid to your concoction there buddy?

        1. Ed Dwulet says:

          Asshole: Zinc Ionophore Activity of Quercetin and Epigallocatechin-gallate: From Hepa 1-6 Cells to a Liposome Model

          1. Ricardo Bocus says:

            Saw someone in youtube discussing loss of smell as a symptom of Covid and talked about the possibility: anosmia/hyposmia <— carbonic anhydrase VI deficiency <— [Zn deficiency and/or increase of its demand during an infection]

        2. Tee says:

          What a jerk you are, buddy

  21. Bryan says:

    Quercetin Ended up quite high in the ORNL computational screen for drug candidates. Whether it works in people is another question.

  22. John Sendrey says:

    The MD on MedCram does a fairly good job of explaining the possible mechanism of Chloroquine & Zinc Treatment Combo on COVID-19.

    1. Ed Dwulet says:

      The one thing I can think of about those in vitro studies is that the lack of Zn in cells without the chloroquine is very simplistic since lots of things could theoretically chelate zinc and help facilitate transport into the cell, even without chloroquine. And there is some evidence that quercetin (and probably other polyphenols like tumeric) can act as dietary ionophores for zinc:

  23. Thomas McEntee says:

    Interesting price info from Wikipedia entry for chloroquine: “The wholesale cost in the developing world is about US$0.04.[9] In the United States, it costs about US$5.30 per dose.[1]”

  24. Fenichel says:

    Even short courses of chloroquine present a real risk (hemolytic anemia) to people with glucose-6-phosphate dehydrogenase deficiency. This condition is not rare especially in people of West African ancestry.

  25. A student says:

    This zinc-containing phosphatase- might it also contain iron, and if you ask nicely manganese? If so, I had a similar experience, but never made it to elemental analysis since the molecule had other problems. Hell of a protein… built a lot of character.

  26. Opinion says:

    The coronavirus is yet another example that no one in the biological or chemical sciences has a clue what they are doing…..a ton of hot air, argument from authority, and poor thinking has brought us to the point where we can’t even fathom a way to even slow even a moderately dangerous virus. Hopefully this will wake everyone up to the fact that everyone in their field can spend their whole career as a top scientist and literally be cranking out useless academic junk.

    1. Wortle Wordswart says:

      Fair point. Although to be fair the virus has only functionally existed for a few short months (we assume). As a chemist done time on the receiving end of cell biology, seems to me that even if biochemistry an order of magnitude or two less fuzzy, still be no mean feat to come up with a therapy in shining armour that could rescue us fast enough. Apocalypse permitting, no doubt in a century or two’s time scientists will look back on our era as we look back on the eras of Lister and leeches. But that’s no help now.

      Always great fun pricking over inflated balloons. With that, I’ll get off my soapbox, go panic borrowing library books and self isolate as lonely as a cloud until all at once I see a crowd, a host, of golden daffodils…

      1. Nick says:

        This article from about 4 year ago sounds pretty close to the mark.

        1. BOF alias WW says:

          Thanks for that. Fired off to printer and set upon with with highlighter pen. Hard going for old buffer unsteeped in antivirals. Multicentre paper, centres include Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China, located in region universally acknowledged as first epicentre of Covid-19 pandemic.

          Thrust is that a (the?) SARS-CoV virus characterised around 5 years ago as circulating in Chinese horseshoe bats? As stated on p 1512, para 2:

          “…Testing in nonhuman primates is required to translate these finding into pathogenic potential in humans.”

          Followed by load of caveats around such studies, including “US government–mandated pause on gain-of-function (GOF) studies.” More on this in footnote 22:

          Plenty to ponder. Wheyup – just posted on Linkedin, annotated paper from the State Key Laboratory of Emerging Infectious Diseases, Hong Kong Univ (VCC Cheng et al, Clin Microbiol Rev 2007, 660-694). Thank you highlighter with the green and yellow pens. As concluded on p 683:


          …The presence of large reservoirs of SARS-Cov-like viruses in horseshoe bats, together with the culture of eating exotic animals in Southern China, is a time bomb. The possibility of the reemergence of SARS and other novel viruses from animals or laboratories and therefore the need for preparedness should not be ignored.”

          As first commenter on Linkedin thread notes:

          “This paper has largely been under the radar for the past 13 years. Scientific findings do not automatically trickle upwards to the powers that be. What efforts were made to make these findings known to authorities? Science communication to induce governmental action requires a different expertise than microbiology/virology.”

          Bombs away. Irony of life, forward, backward, and all that.

  27. Stanislav Radl says:

    Chloroquine played important part in the MedChem history. It was also at the beginning of the discovery of quinolone class of antibacterials. During antibacterial screening at Sterling, they screened also some impurities from their chloroquine production and found one of them, 7-chloro-1-ethyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, active against G(-) strains. Modification of the structure led to nalidixic acid, the first drug of the class.
    Since I worked in the field for years, both in Prague and at Roche in Nutlkey, I have also published a review on the subject “ From Chloroquine to Antineoplastic Drugs? The Story of Antibacterial Quinolones“ –

  28. Cb says:

    It has been shown that alteration of N-linked glycans of ACE2 does impair the CoV envelope spike glycoprotein-triggered membrane fusion. If chloroquine would be effective by disturbing the biosynthesis of N-glycans (e.g. lowering lysosomal pH or direct enzyme inhibition) some glucosidase I and II inhibitors may be more effective. Indeed numerous derivatives of 1-deoxynojirimycin and castanospermine (iminosugars from e.g. leaves and seeds) have been investigated as broad-spectrum antiviral agents including CoV type inhibition. N-butyl-1-deoxynojirimycin (Miglustat) is an existing drug that reduces the above mentioned fusion in models, but other derivatives are more potent.
    Antimicrob Agents Chemother 2015, 59:206 –216. doi:10.1128/AAC.03999-14.

  29. Paul Thomas says:

    I took chloroquine for years in Congo as prophylaxis and treatment. No side effects.

    So did a lot of other people.

    1. Derek Lowe says:

      Definitely. But it does have such effects in a percentage of the population. My thinking is that if tens of millions of people try to take it prophylactically, we could see some trouble. I think even if it works it’s going to be more of a treatment once you’re very sick.

      1. John Beach says:

        Is enough known to write a story on how chloroquine metabolizes differently for people with cytochrome polymorphisms?

    2. Drug developer says:

      I took it for 2 years in Africa in the mid-80s. Only side effect: crazy technicolor dreams!

  30. GarthRp says:

    The best description of chloroquine virus entry MOA and in vivo activity – see Madrid PB,, et al. (2013) A Systematic Screen of FDA-Approved Drugs for Inhibitors of Biological Threat Agents. PLoS ONE 8(4): e60579. doi:10.1371/journal.pone.0060579. Nice paper.

    The EC50s against highly pathogenic CoVs similar. Time of addition favors CQ use as primary prevention only (see Vincent et al, Virology Journal 2005, 2:69)
    As of today, 2800 infected frontline healthcare professionals in Italy are infected. Daily administration (200mg hydroxyCQ) should block infectivity.

  31. Luke Mullen says:

    Hello Derek,

    Although you mentioned the fascinating French study showing success with Chloroquine; you did not mention the equality fascinating medical literature in both South Korea and China, describing Chloroquine’s success.

    Please watch this MedCram MD’s video describing & citing such South Korean & Chinese Medical literature …

    1. Toni says:

      Hmm? I don’t know, but the chloroquine concentrations would have to be huge (more than100µM) to get halfway necessary amount of zinc into the cell. At least the theory is nice.

  32. Craig says:

    Whatever happened to the DRACO antiviral project?

    If it worked would it be effective against coronaviruses?

    1. M says:

      Rider is a remarkable talent. If DRACO doesn’t work in people, Im very curious as to why not.

      1. loupgarous says:

        DRACOs have this one scary little thing about them: they kill infected cells, not viruses. Great of you catch the infection before it goes systemic. But in COVID-19, the people who are dying are succumbing to a cytokine kinase storm. It’s hard to see how DRACOs would help those patients.

        And catching COVID-19 patients early enough in the disease process where massive death of infected cells doesn’t create issues worse than the disease itself is problematic.

        Between a quarter and a half of all COVID-19 infectees don’t have symptoms – but do have infected cells. What would DRACO do to those people? I don’t know, and I’m not sure anyone does, but renal overload by fragments of cells which have died and been tagged for destruction is a possibility.

    2. Florian Kogel says:

      This would be the perfect time to put DRACO into focus again. I saw that a petition has been initiated on to suggest DRACO to WHO and other institutions (

  33. Jeff Goodson says:

    For those of us who took a lot of chloroquin in the old days to ward off malaria–I spent two years in the African bush in the mid-1970s–the thought that it might make a comeback brings mixed emotions. I caught malaria anyway, and the impact of the drug on everything from eyesight to liver function was hotly debated. Presumably, the medical and pharmaceutical professions have a lot better understanding of side effects of the drug today.

    1. Victoria Coghlan says:

      I took 200mg of Plaquenil daily for over 8 years to treat atypical Lupus. Was able to reduce to my dosage of corticosteroids which took a terrible toll on my body and eyesight. Plaquenil was well tolerated. I would absolutely take it again should I test positive for Covid-19. Finding a physician to prescribe it is my only concern.

  34. Jenifer Caplan says:

    Any thoughts on using Methlyblue?

    1. Derek Lowe says:

      Do you mean Methylene Blue? Not recommended. . .

      1. Jenifer Caplan says:

        Why not? It works on malaria better then hydroquinone

        There are studies that it kills covid-19 in blood

        There are mitochondrial benefits and it delays aging. Also it works with light so if you take it and go out in the sunlight it can work even better.

        Studies showing it helps cure pneumonia

        So I was curious if it may have a similar effect on covid-19

        1. Tyler Jordan says:

          Methylene blue works by assisting with oxygen transfer, it’s not anti-viral or anti-malaria – just helps with oxygen which can be good for pneumonia and malaria, but won’t stop viral replication or really affect the virus at all.

          1. Jenifer says:

            Then why is it used to kill the Covid- 19 virus in those studies in the blood?

            Do you for sure know that it cant do the same thing as the pharmaceutical malaria drug. From what I understand that hydroquinine performs two functions. Increase non permeability of the cell wall making it a it more acidic and the virus proteins have ( less ability to cleave) and also deactivation of the receptor sites as well. Do we know that MB does not do the same thing. I am not advocating it I just used it for bio hacking the mitochondria and knew it was better at treating malaria then the hydroquinine ( at least that is what a 2018 study suggested).

          2. Jenifer says:

            Then why is it used to kill the Covid- 19 virus in those studies in the blood?

            Do you for sure know that it cant do the same thing as the pharmaceutical malaria drug. From what I understand that hydroxychloroquine performs two functions. Increase non permeability of the cell wall making it a it more acidic and the virus proteins have ( less ability to cleave) and also deactivation of the receptor sites as well. Do we know that MB does not do the same thing. I am not advocating it I just used it for bio hacking the mitochondria and knew it was better at treating malaria then the hydroxychloroquine ( at least that is what a 2018 study suggested).

  35. Derek, I’m surprised by your relatively negative take on hydroxychloroquine. Pretty widely used drug, and as several have noted, relatively benign. For short-term antiviral treatment, perhaps the possibility of QT prolongation is most concerning. So is dying of SARS-CoV-2, on the other hand.
    We’ll see what larger trials show; in the meantime, (at least some) mechanisms make sense, and in vivo animal studies look pretty good.

    1. Derek Lowe says:

      I’m all for it if we figure out that it’s effective and have a dosing recommendation. I worry, though, that a lot of people are going to “grab and gulp”, which is not a good plan.

  36. P.S. – Glad to see chemical structures make their return to the blog!

    P.P.S. – Layout (at least on iPhone) is confusing. “Structure at right” is often elsewhere …

    1. Nkj says:

      Try flipping the iPhone horizontally

  37. Mark Thompson says:

    We need to stop being trapped by the paradox of expertise and waiting for the gold standard proofs of controlled trials. Crisis calls for breaking rules and innovating. Treatments already approved for other conditions should be applied widely now, and proofs can wait til later. I have great respect for our medical professionals, but this is not a time for the typical level of caution that they have all grown up in. This is a classic example of the a paradox of expertise.

    1. Collateral Damage says:

      “This is a classic example of the a paradox of expertise.” or Dunning-Krueger syndrome?

    2. loupgarous says:

      We’re discussing chloroquine and its derivative hydroxychloroquine here. There’s a lot of real-world experience with these drugs. They’re not innocuous drugs, and shouldn’t be prescribed without a real expectation the patient will benefit from their use enough that it’ll be worth physical injury they’ll suffer from taking them. The existing rules regarding the use of these drugs evolved because people have been injured by them.

      The paradox of expertise can be resolved to one question: who gets to be the experimental animal in which the effectiveness of chloroquine or hydroxychloroquine in treatment of COVID-19 are measured? Wife? Mother? Brother who’s high-risk because radiation and/or cancer wore his immune system down? Neighbor? Maybe some family in China or India?

      I’ve done clinical trials before, ones of not-innocuous treatments which offered great benefit, and mostly I did well. I wouldn’t mind being a Phase II volunteer in a study of chloroquine or hydroxychloroquine with azithromycin for COVID-19. Hopefully I won’t be a candidate for Phase III, but if that’s how it works out, sure, let’s go.

      So my evening’s planned – to see if anyone in my geographic area’s got a study.

      1. loupgarous says:

        oops. “”. You’d think I’d have that one memorized 🙂

  38. A Nonny Mouse says:

    Interesting to see that a study was initiated on 6th February….with completion in December!

  39. Rick Wobbe says:

    Lessons from history… Chloroquines have been suggested as possible “broad spectrum antivirals” for decades based on in vitro results and even animal models only to yield disappointing or negative clinical results. Example include influenza (Lancet Infect Dis. 2011 Sep;11(9):677-83.); dengue (PLoS Negl Trop Dis. 2010 Aug 10;4(8)); chikungunya (where it may stimulate replication in patients, Viruses. 2018 May 17;10(5)). Moreover, unwarranted prescription of these drugs for COVID19 is reported to be threatening their supply for people (~ 10 million in the US alone) suffering from one of the approved indications (including Rheumatoid arthritis, Lupus erythematosus, Malaria, Dermatomyositis, Porphyria cutanea tarda, Sjögren syndrome, Q fever, Sarcoidosis, arthropathy).

  40. Joker says:

    We know where the disease came from!
    The culprit’s (obviously) Batman.

    PS Jokes are good for health. I hope to read about joke discovery too.

  41. James Steinmetz says:

    If chloroquin by itself is exerting anti-coronal virus effects then that is serindipitous because it’s greatest value as a treatment for the Covid-19/SARS-2 infection involves chloroquin being a zinc ionopjore. Intracellular zinc was shown to inhibit the production of the viral replicase polypeptide. Viral replicase is what is read by the host cell to produce the virions that are the cause of the continuing infection of the human host. The problem is that positively charged zinc ions (+2) cannot get through the phospholipid bilayer easily. This is where chloroquin shines because it, as acts as a zinc ionophore opening up a zinc ion transport channel through which extracellular zinc can then pass through via diffusion. Once inside the cell space zinc can then act to inhibit replicase transcription and stop the formation of the replicase which in turn suppresses the production of the proteins that make up the virions. Less virions allows are immune system to attack the invading viruses and the few virions produced thus decreasing the severity and duration of the illness.
    My questions are whether or not quinine itself is a zinc ionophore , what other substances are zinc ionophores and would the use of Micellular Zinc which is zinc coated in a lipid compound (usually stearic acid or stearate) be as effective as using chloroquin to transport extracellular zinc into the intracellular space?

    1. Jack says:

      Great question James Steinmetz – I hope someone deigns to answer you.

      1. Ed Dwulet says:

        OK both you guys — here’s your answer — posted earlier — guess you missed it:

    2. M says:

      Would quercetin help zinc enter the cells like hyroxychloriquine?

    3. Jimbo says:

      Green tea and queritin are ionospheres. There is no dosing info. Just drink your green tea and take your Zn supplements till the bureaucrats get out of the way of HCQ and big pharma is DPA’d into ctanking it out.
      Trump won’t put up with private agendas.

      1. Hika says:

        Trump is all private agenda.

  42. Mike says:

    Is it correct that source of the chloroquine is a seed called negila savita?

    1. Alia says:

      You probably mean Nigella sativa, love-in-the-mist. And no, I don’t know.

    2. Liz Wallis says:

      No, that’s thymoquine. Not related.

      1. Liz Wallis says:

        Whoops, try that one again. Thymoquinone. Still not related.

  43. loupgarous says:

    What do we think about this article in Bloomberg News? “Virus Drug Touted by Trump, Musk Can Kill With Just Two Gram Dose” – Bloomberg News – March 20, 2020, 1:50 AM CDT Updated on March 20, 2020, 4:09 AM CDT

    The implication is that chloroquine is deadly in commonly prescribed doses. That’s lying by both suggestio falsi and suppresio veri. The article trots out the scary stuff at the top of the “inverted pyramid” and saves the less distressing explanations for the end of the article, which readers rarely reach in a busy day.

    Missing from the article entirely is the risk/benefit calculation physicians must make in treating COVID-19. Chloroquine may or may not be a safe prophylactic medication over a period of weeks, but the choice facing many is a sure death once COVID-19 takes hold in an elderly or immunosuppressed person versus the chance of suffering toxic side effects if chloroquine and azithromycin prove to be effective against the infection.

    Bloomberg is playing P.T. Barnum here (“This Way to the Egress”), playing with words to imply what clearly isn’t true.

    1. Anonymous says:

      I have to admit that this Mar 24, 2020 Clinton tweet was pretty good: “Do not take medical advice from a man who looked directly at a solar eclipse.”

  44. Philippe says:

    Super interesting article. By which date, do you expect the scientific community to know if this could or not be a highly efficient solution against CV19?

  45. sgcox says:

    There are millions (?) of RA pationts across the world who take hydroxycloroqine daily.
    Surely there must be enough data collected by now to see if there is any prophylactic or treatment effects ?

  46. atl-qui says:

    is quinine as effective as chloroquine against viral infection?

  47. Nicholas Sorenson says:

    I’ve taken both mefloquine/chloroquine and probably handful of other antimalarials (depending on regional resistance) over the past 20 years while working in west Africa / Southeast Asia and never had issues, though I have know quite a few people who did have severe reactions. The one layman’s question I do have for this forum is about the potential efficacy of non quinine based antimalarials in this scenario – would Atovaquone-Proguanil (malarone) for instance be considered a candidate for Covid-19 or am I barking up the wrong tree?

    1. J B says:

      Did you get an answer on this? I just returned from the East and have this med (Atovaqoune and proguanil) on hand.

  48. Sean Fhearsalach says:

    people are alreday overdosing themselves with chloroquine in Nigeria. See

    1. loupgarous says:

      This is just another yellow journalism hit-piece – between “Nigeria Has Chloroquine Poisonings After Trump Praised Drug” and “Virus Drug Touted by Trump, Musk Can Kill With Just Two Gram Dose”, Bloomberg news has decided to push the post hoc, ergo propter hoc fallacy hard – “Trump praised this drug, bad things happened when people overdosed on it, therefore (lead the reader to an entirely inappropriate conclusion wish slanted reporting)”. You don’t have to think Trump even came close to handling this crisis properly to recognize garbage reporting that insults the intelligence of its readers when you see it.

      I’ve praised Bloomberg News on its pharma reporting here before. Never again.

      Mike Bloomberg’s out-Hearsting William Randolph Hearst.

  49. Zoya says:

    Govt of India is recommending Hydroxy chloroquine for prophylaxis of SARS-CoV-2 infection for following:
    1) asymptomatic healthcare providers involved in care of suspected or confirmed cases of Covid-19
    Dosage -400mg twice a day on day 1
    400mg once a day for next 7 weeks
    2)asymptomatic household contacts of confirmed cases
    Dosage-400mg twice a day in day 1
    400mg once a day for next 3 weeks
    Standard precautions ( to be taken with meals) and side effects mentioned.

  50. Shirley Schreier says:

    Dear Derek
    When you wrote trypanosomes, tou meant Plasmodia, right?

    1. Derek Lowe says:

      I keep forgetting to fix that! Done. . .

  51. Daniel Perry says:

    Would you think mefloquine would have the same beneficial effects as chloroquine regarding coronovirus? I took mefloquine as an anti-malarial for many years with no ill effects.

  52. wilmar says:

    Interesting report with regard to mefloquine:

  53. Nige says:

    Interesting blog!
    I noticed Africa & some midfle east countries largely unaffected…. anti-malarial drugs the former… curcumin used in cooking the latter..Morroco..
    Clinical trials …Australia557 per 100k, South Korea 549 , UK 117, USA 22, Austria 265 n France 57.

    1. Derek Lowe says:

      I fear these numbers could be artifacts of low rates of testing. For what it’s worth, Ivory Coast has declared a state of emergency.

  54. Lynn says:

    And, now, a death from people self medicating. A couple in Arizona took chloroquine phosphate that they had for their aquarium, to treat fish. Husband died pretty quickly and the wife is very ill.

    1. Anonymous says:

      Lynn, Arizona chloroquine death: Does anyone know if aquarium chloroquine phosphate has additional ingredients not found in human medical chloroquine? (I can’t find a bottle label or ingredients list using google.) Or was this a huge overdose problem?

      1. Toni says:

        allegedly they took a “spoon”. Depending on the size, there should be at least 1 gram in there.
        Just out of curiosity about the supposed harmlessness of chloroquine.

        “The Paris society, which promotes voluntary suicide, recommends chloroquine to its members as a potentially toxic drug which is easily obtainable over the counter”

        1. loupgarous says:

          “Just out of curiosity about the supposed harmlessness of chloroquine.

          I don’t recall anyone notable calling chloroquine or any quinine derivative “harmless”. Almost everyone reading this knows Paracelsus’ maxim Sola dosis facit venenum “Only the dose makes the poison” – a succinct statement of the dose-response relationship.

          Although Trump was too lyrical about chloroquine’s effectiveness in treatment of Covid-19 on scant evidence, nothing he said would cause a reasonable adult to take too much of it and die. Reaching for reasons this obscure to criticize someone induces a kind of Streisand effect in the audience.

          1. Anonymous says:

            loupgarous, “nothing he said would cause a reasonable adult to take too much of it and die” : Unless you are limiting the discussion to Lake Wobegon “where all the children are above average”, half of the US population has below average “reasonableness.”

            Trump should not be making medical pronouncements (except when ACCURATELY quoting actual medical authorities) from the lectern as POTUS: people of all levels of reasonableness are listening to him and many are believing him. In The Pipeline is not the place to provide a long list of falsehoods that Trump has touted and that many Americans still believe to be true because “Trump said so.”

      2. loupgarous says:

        Apparently, it’s a crapshoot going through aquarium suppliers for medication whether or not you get what you’re paying for. This article from a New Mexico news station describes massive fish kills allegedly from mislabeled aquarium additives

        “The Texas State Aquarium in Corpus Christi had almost 400 fish die one month ago Thursday when they tried to get rid of parasites. They launched a full investigation and learned, this is a matter of mislabeling. Instead of getting the drug to treat fish parasites called trichlorfon, the supplier shipped the aquariums a chemical used in film processing and a stabilizer for pain and motor fuels called hydroquinone, according to a news release by the Texas State Aquarium.”

  55. Grim Reaper says:

    There is your front runner for next years Darwin Award.

  56. Patricia Anne says:

    And a recap from Yahoo News Aggregate:
    “The French study has attracted the most attention. Doctors gave hydroxychloroquine to 26 people with confirmed coronavirus infections, including some with no symptoms. Six also were given the antibiotic azithromycin.
    Some of the 26 were not counted in the final results because they didn’t complete the study — what’s known as “lost to followup” — but that included three who worsened and were sent to intensive care, one who died a day after later testing negative for the virus, and one who stopped treatment because of nausea.
    After six days, no patients given hydroxychloroquine plus azithromycin had virus detected in swabs from the back of the nose, versus 57% of those given the malaria drug alone and 12.5% of some other patients who received neither drug.

    And this from Gov. Cuomo’s website:
    Acquires 70,000 Doses of Hydroxychloroquine, 10,000 doses of Zithromax and 750,000 Doses of Chloroquine to Implement Drug Trials – Trials Will Start Tuesday

  57. Patricia Anne says:

    Derek: As a non-professional in any science, I was lost in your zinc references.

    Do zinc-based, OTC meds such as Zicam, have any anti-viral properties? Or rather, has zinc been shown to have anti-viral properties?

    1. Derek Lowe says:

      There’s some evidence that zinc lozenges can shorten the duration of a cold, but not its severity. Other viruses? No idea.

  58. Ron T says:

    Derek, my wife says I need to contact CDC or someone with my successful use of Cinchona Bark tea (quinine quinidine) against my unconfirmed Covid infection.

    I believe my case shows evidence of the efficacy of Quinine because on Day 6-12 I had much improved symptoms after developing a concrete lung feeling and on Day 5 a drowining feeling. But when I stopped the Quinine for 24 hours on Day 12. (out of concern for the recent press about side effects), within 24 hours I went to having severe breathing difficulties and literally feeling like I was drowning. I made the choice to drink the tea as preferable to dying. An hour later I was able to sleep. Now 37 hours later I feel excellent.

    My urgent care visits in Day 3 and 14 both showed completely clear lungs with no hint of any infection.

    My oxygen on Day 14 was still 99% even though I felt slightly hypoxic. Is there some way the fingertip oxygen test was fooled by the virus? I read a chinese paper referenced below that somehow covid attacks hemoglobin. It’s above my education level.

    Please help me understand why these worked. I hear the zinc allowed in theory and the endosome prevention theory. What do you think is really going on?

    And please email me who I should contact. I believe this is evidence – the stopping and starting of quinine correlating exactly to my symptoms is evidence.

    On Day 1 I woke up with “concrete chest tightness”. On Day 3 I was not tested for covid because I never had a fever.

    On Day 5 I woke up gasping for air.

    On Day 6 I bought Red Cinchona Bark tea and took the “traditional dose” I researched online (1-3 grams day). By the afternoon I had immediate improvement.

    Day 6-12 I had no chest tightness, but had strange symptoms moving through parts of my body, such as a moving full feeling in various parts of my lungs.

    Day 12 stopped Quinine out of fear for mis dose, QT prolongation etc

    Day 12-14 above. Once I show no symptoms for three days I can leave self quarantine.

    1. Becky Francis says:

      Ron T could you please email me

    2. Thanks for this Ron T. I came across some leg cramp pills from Hylands that has the cinchona ingredient in them for my girlfriend when her lungs were hurting so bad that she couldn’t hardly move. They would not even see her at the doctor for the same reasons you say, no fever. I started researching and found out about this Peruvian bark. Went out immediately and purchased this over the counter leg cramp medicine. It has been 2 days now of taking it and she feels like a new Person! She is by no way healed yet but her pain has diminished and she is on the upswing. Cant believe it!

      She is trying to help by telling people and I feel like trying to tell the CDC will for certain go upon deaf ears. She has existing health problems due to a car accident causing her to be more susceptible to infection. She is missing half of one of her lungs and doesn’t have a spleen.

      It is nice to see someone experiencing the same results. She felt immensely better in the hour after her first dose.

    3. Tiffany Simon says:

      Where did you obtain the tea? I’m curious as it’s sounds as though it might have been useful. I also read drinking hot beverages constantly if you start noticing symptoms

  59. Becky says:

    Ron t….. I have cinchona bark what is as your tea recipe and dosage

    1. Ron T says:

      I found online the traditional cinchona tea recipe/dose was 1-3 grams a day for malaria. I used this dose because I found Chinas current recommended dose of hChloroquine for covid was the same dose widely used for once you have malaria (not the prophylactic malaria dose which is much less.)

      Chemistry people on here could look it up (please do) but near as I could tell 1 gram of red cinchona equals about 1 400mg hchloroquine pill. So I’m doing 1 gram of tea in morning and 1 gram at night.

      Warning: 6 grams is fatal!

      To measure I used 1/4 a teaspoon for 1 gram. Steep in boiling water for 7 minutes. I include large and small bark particles evenly, avoid just using dust because the dose will be too strong.

      The half life is 6 hours.

      1. Derek Lowe says:

        Folks, I do not want this to become a forum for self-dosing recipes, etc. Please take this to some other means of communication – thanks!

  60. Ashutosh says:

    Great information about chemistry with natural product .Regard

  61. Andy Holland says:

    Studies with SARS-1 and Chloroquine showed great promise 15 years ago! How much do we spend on the CDC and FDA? What do we get for our tax money? There is a reason they used to call cures “anecdotes”. In a global world with advanced statistics, methods and data, using human beings as lab rats for FDA studies is wrong. Medicine needs to advance and controlled experiments with human “controls” is arcane and frankly unnecessary. It might fit an old fashioned “scientific” cookbook, but it is not advancing the art.

  62. P One says:

    Has anyone seen this letter published by a doctor in New York, where he has constructed a protocol based on hydroxychloroquine?

    It is definitely not a study, but unless he has been dishonest with his data, he is claiming not a single hospitalization (!) let alone intubation out of 500 patients subjected to his protocol checklist.

    Since the speculated mechanism of action for chloroquine is to allow large amounts of zinc into the cell, where it interferes with viral reproduction, it makes sense that a successful use of that drug might require its very early use in the disease process. That would allow viral loads to be significantly drawn down before they can create an overwhelming inflammatory response.

    Without validating his use of the drug, I am wondering what are the statistical chances of his patient population having zero hospitalizations? That seems nearly impossible, and would therefore suggest something about his protocol probably made a material difference to the outcomes.

  63. HCG says:

    Those who criticize that the off-label and compassionate use of HQ + AZ during this ongoing pandemic disregard one important point: these drugs, are already available. Given some indication from empirical data from physicians that they do work, why can’t the drugs be used?

    The adverse effects of HQ (in particular) are overplayed: it and chloroquine have been widely taken as chemoprophylactics against malaria. The benefits (e.g., against
    pneumonia and fatality in the time of a spreading pandemic) vastly outweigh the risks (cardiac arrhythmia, blindness, etc.).

  64. HCG says:

    The ethics of clinical trials investigating the efficacy of HQ/chloroquine in the time of a rapidly spreading coronavirus pandemic needs to be examined. Are the controls placebo-treated? If so, how morally correct is it to watch them become infected, become sicker, or die merely to compare them with those given the drug? And, how ‘blind’ is the trial? Will subjects given the drug who survive not know they are or not given the drug?

    1. JP Leonard says:

      To deal with ethical issues, how about a trial where half the patients get HCQ and half get the placebo for the first 3 days, then it’s switched around and those who got HCQ now get the placebo (and vice versa) for the next 3 days. Double blind. Then compare their charts for the two 3-day periods and see if they did better on the HCQ days. Since HCQ is most useful early on when symptoms are not critical, the ethical risk can be reduced by doing this trial where the symptoms are relatively mild. Sharing risk, “I scratch your back and you scratch mine.”
      However, we could be focusing too closely on HCQ. The real benefit might be via bio-available zinc. So I would test all Covirus patients for zinc deficiency, and control for that in trials too.
      It might turn out that HCQ mostly helps in cases with zinc deficiency. This would confirm the zinc transfer hypothesis. Also, expand trials to include other zinc ionophores, such as Quercetin.

      1. Natasha Nolan says:

        Do you have info showing Quercitin and zinc creating ionophores?

  65. wilmar says:

    It would be interesting to investigate the effectiveness of using isoquinoline alkaloids to prevent infection with corona type viruses.
    Some studies are pointing towards the need of preventive usage of isoquinoline alkaloids. See

  66. MIGUEL says:

    if you want to know the thru medicine to cure malaria go to you may learn a lot from him also quantum leap on google good evidence videos of red cross in africa

  67. Mohammad Issak says:

    using vapor of 20-30% ethanol can improve covid-19 patient, how much possible?

  68. Mohammad Issak says:

    gargle with 20-30% ethanol can remedy covid-19 patient, how much possible?

  69. Jeff says:

    Handing out Oxy like candy for years with no concern for the patient. I have to laugh about all the fake concern in every thread about this drug.

  70. Craig says:

    This is one of the most informative articles I’ve read about CQ/HCQ and I’ve read a LOT!

    I came away with much more useful information than I was seeking!

  71. Gustavo Henrique Orair says:

    Any medicine study on atazanavir?
    “The result showed that atazanavir, an antiretroviral medication used to treat and prevent the human immunodeficiency virus (HIV), is the best chemical compound, showing a inhibitory potency with Kd of 94.94 nM against the 2019-nCoV 3C-like proteinase, followed by efavirenz (199.17 nM), ritonavir (204.05 nM), and dolutegravir (336.91 nM). Interestingly, lopinavir, ritonavir, and darunavir are all designed to target viral proteinases. However, in our prediction, they may also bind to the replication complex components of 2019-nCoV with an inhibitory potency with Kd < 1000 nM. In addition, we also found that several antiviral agents, such as Kaletra, could be used for the treatment of 2019-nCoV, although there is no real-world evidence supporting the prediction."
    "Next, a series of assays with in vitro models of virus infection/replications were performed using three cell types, Vero cells, a human pulmonary epithelial cell line and primary human monocytes, which confirmed that ATV could inhibit SARS-CoV-2 replication, alone or in combination with ritonavir (RTV). In addition, the virus-induced levels of IL-6 and TNF-α were reduced in the presence of these drugs, which performed better than chloroquine, a compound recognized for its anti-viral and anti-inflammatory activities."

  72. Donna says:

    For the chemists, is the supplement Pyrroloquinoline quinone (PQQ) an effective replacement for quinine or chroloquine? Thanks in advance. And thanks for the in depth info and chat, has been very informative.

    1. J0eshm0e says:

      I heard that the Pyrroloquinoline Quinone taken with Zink Citrate has the same effect as Hydroxychloroquine but i have been able to find any evidence to confirm that. Did you ever find the answer to your question?

  73. Bog says:

    In three days we will be all dead or safe because of the meteorite shower going to hit, or miss the Earth on April 20. Next week forward the coronavirus plague will be the least of everybody’s problem, or miraculously dissipating, all over the world, mark my word. They keep people home for a good reason, and that is not coronavirus – although just in case I am taking quinine 500mg and amoxicillin 500 mg any time before making the trip for food to the closest store. Unfortunately I do not qualify for the seat on the spaceship under the White House, and it is far from where I am to the closest hills so I am spending most of my time praying instead. Considering the context, the side effects of using chloroquine seem to be of tertiary importance; And yes, chloroquine is being widely and officially used in Poland against Covid 19, so perhaps they know something first hand from Chairman Xi, or Pres. Trump, the latter obviously playing together with dr. Fauci simply the good guy – bad guy routine. What would you expect, for Fauci to step forward and cry “…go for it, idiots!”?. It is left up to Trump to spell it out, exactly because he is not a specialist. The role of idiot savant is clearly his specialty, but I would advise everybody to dig out some old videos of him. A bully showman type, no doubt, but quite coherent, shrewd and to the point. I have no horse in the election game, just stating the obvious.

    1. Tee says:

      Fauci is corrupt.

  74. zoe says:

    There is so much hypocrisy in the “precautionary” comments here. Remember: IT IS A MEDICATION THAT REQUIRES A PRESCRIPTION!!!! People ARE NOT ingesting it anytime/anyway – as it does not grow on trees. Plus, these “well wishing” pseudoscientists (please read morons) are so concerned that someone might get diarrhea, retinal changes or arrhythmia while on their death bed. Sure, if they get infected with COVID-19, they prefer to die proudly and not take hydroxycloroquine and live with some decline in visual acuity.

  75. Gwen says:

    I always think the natural source (cinchona bark) is best. While I understand the chemist’s desire to isolate the active compound, side affects always seem a drawback to pharmaceuticals. Nature provides the medicinal qualities within the plant along with other elements, perhaps a more wholesome tonic. Of course anything taken in excess is toxic, even water. However, I am inclined to use herbs sparingly and in their natural form, considering nature has evolved them and the human body has developed “recognition” (I don’t know the scientific term) of natural herbs and fruits over the eons. . I am not a doctor or scientist, just a simple person who respects the natural world, It’s gifts, benign and toxic! 🌿 🌏

  76. fran says:

    Early phase of Covid-19: 400mg Hydroxychloroquine with zinc, 200mg 2 xs a day for 4-5 days., and if needed add Ivermectin. Also if needed azithromycin or doxy…SARS COV (the first one) was inhibited by Chloroquin in 2005 virology report. SARS COV 2 is 78% the same as the first SARS COV. This is only a repeated antidote that I have heard many doctors who have successfully treated Covid- 19. However, most states governors have put a ban on HCQ for the treatment for Covid-19. Pretty messed up.

    1. Derek Lowe says:

      That 2005 paper was in vitro. Not in people. Big, big difference.

  77. Charlotte says:

    Hydroxychloroquine: A Morality Tale

    Norman Doidge, a contributing writer for Tablet, is a psychiatrist, psychoanalyst, and author of The Brain That Changes Itself and The Brain’s Way of Healing.

  78. Charlotte says:

    New peer reviewed study from The Journal of Electrocardiology concludes that #HCQ with Azithromycin did NOT have any QT prolongation issues in non-ICU patients.

    It is considered safe!!!

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