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Known Drugs Being Tried Against the Coronavirus: Runner-Up Candidates

Everyone’s heard plenty about chloroquine, azithromycin, remdesivir and other front-running ideas for anti-coronovirus therapies. Today I wanted to focus on some compounds that haven’t gotten as much attention but which have been proposed from more than one place as possibilities. Some of these have shown up in the comments to past posts here, for example. Do any of them look reasonable? We’ll take four, in no particular order.

First up is Alvesco (ciclesonide), a steroid derivative for asthma, allergies, etc. It’s a glucocorticoid, and there are several of those used for just those indications. But ciclesonide in particular seems to have come up as a hit in drug-repurposing screens, suggesting that it’s not working through its traditional mechanisms. Indeed, there’s now a report that it suppresses replication of the novel coronavirus, but not influenza or RSV. That same paper identifies the viral NSP15 protein (an endonuclease) as the possible target. Repeated passaging of viral infection in the presence of the drug generated a resistant mutant (A25V) of NSP15, which is good evidence. The protein-protein interaction paper that I blogged about yesterday identified NSP15 as targeting human proteins involved in nuclear transport machinery (NUTF2), endocyctic recycling and cytoskeletal remodeling (ARF6) and in evading the innate immune system (through targeting the E3 ligase RNF41/Nrdp1). Those were the main interactions detected for that protein, so it’s possible that ciclesonide is working through disruption of one of those. (That protein-protein paper itself did not pick up ciclesonide as a possible repurposed drug, since it was looking mostly at repurposing known mechanisms, and not completely new hits like this one seems to be). There is a trial getting underway in Japan, in patients who have tested positive but are still asymptomatic, and we’ll see what happens.

The next compound is Niclosamide, which is an antiparasitic drug from the 1950s. Like many compounds in that area, it has a wide range of mechanisms, and has over the years been repurposed for all sorts of things – for example, as a fish poison, particularly for lampreys. Even before this latest epidemic, it had come up in a screen against MERS coronavirus infection, apparently through inhibition of autophagy via the human SKP2 protein, and earlier as an inhibitor of replication of the SARS coronavirus as well. One of those repurposing links in the above paragraph that flagged ciclesonide also picked up on this one, so there are several lines of research pointing in the same direction. That said, niclosamide seems to be quite the shotgun, with plenty of side effects (it’s not even frontline therapy any more for its intended use in tapeworm infection). But it’s been in use in humans for many decades (rather like chloroquine, another old drug with known liabilities) and in the current context it seems to deserve a look. It’s not available commercially in the US, from what I can see, and I am not aware of any controlled trials enrolling.

Then we have Disulfiram, which is another very old compound, famously used in the treatment of alcoholism by producing an acute reaction to alcohol intake by inhibition of acetaldehyde dehydrogenase. In effect, drinking while on disulfiram produces an immediate and horrible hangover, complete with headache, nausea, vertigo, and extreme regret. Of course, a person being treated in this way has to be willing to take disulfiram regularly in the full knowledge that if they don’t that they will experience no such symptoms, so it has always been a relatively niche therapy that is not suitable for every patient. It too had already been identified as having activity against the previous coronavirus pathogens for MERS and SARS and was quickly suggested in this current epidemic. It may work through inhibition of cysteine-containing proteases, but this one is another shotgun, and I would be hesitant to assume too much, mechanistically. I believe that the compound has had supply problems, even before this, but there are some trials shown as “Recruiting” on Clinicaltrials.gov, for Lyme and for various oncology indications. Nothing for coronavirus that I’m aware of.

Finally, we have Nitazoxonide, which is an antiparasitic drug from the 1980s and still the only agent approved in the US against Cryptosporidium. You’ll note a broad similarity to niclosamide, above, although the thiazole ring is important (this compound led to an entire class of thiazolides). And being another blunderbuss, it has shown up in several repurposing efforts over time, and a few years ago went into trials as an anti-influenza drug. In vitro and animal model data (see that link) suggests that it would have broader antiviral activity as well. You’d want to see that in the current situation, because any influenza-specific mechanisms would not be expected to carry over well to coronaviruses (as indeed they haven’t). The thing is, nitazoxonide doesn’t seem to have a single broad-spectrum mechanism – as people have studied it against different viruses, different modes of action seem to come up. It has not made it through all its trials successfully, it has to be noted, but as a broad-spectrum antiviral (one way or another!) it has gotten some attention. I am not aware of any controlled trials underway, although there are reports of its use in the field.

 

 

91 comments on “Known Drugs Being Tried Against the Coronavirus: Runner-Up Candidates”

  1. Barry says:

    It is thought that the anti-parasitic action of nitazoxonide depends on reductive activation by a nitro-reductase that humans lack. Anti-viral activity in vitro or in vivo wouldn’t enjoy that reductive activation. So the nitro group might be replaceable?

    1. TheEdge says:

      Nitazoxinide isn’t effective vs Cryptosporidium in immunocompromised patients (AIDS patients, malnourished children, etc), implying that there is at least some host-based activity, or it simply retards growth enough the host can clear it. It has no in vitro activity in cryptosporidium assays, either.

  2. Noel says:

    With the exception of ciclesonide, this looks a greatest-hits list for high-throughput screening false positives. Compounds sometimes act differently with cells on plastic. Another consideration is what exposure can actually be obtained clinically without harming the patient.

    1. loupgarous says:

      Considering the drug candidates already being considered (today’s runners-up – like Antabuse – included) I’m beginning to think they’ve run out of firm, dry poop to hurl against the wall in hopes some of it sticks. Nitazoxonide in particular has what you might call a “onomatopoeic” structure – it seems to be saying “O No!” at the nitrothiazolyl group.

      I keep expecting someone to announce a study of chloroquinine with an absinthe chaser.

      1. eub says:

        beginning to think they’ve run out of firm, dry poop to hurl against the wall

        I snorted audibly.

        1. Jerome G Buescher says:

          Me too … Also at the next one about the absinthe chaser …

          1. loupgarous says:

            After I wrote that, the thought occurred… “Okay, the oil of wormwood in absinthe got its name from being an alleged cure for worm infestation, and some of the also-rans in Derek’s list are antihelminitics.

            It’s got anti-inflammatory flavonoids in it and thujone in it , another of these lead candidates that does all sorts of things in animal models, but in humans only seems to (in huge doses you never see in absinthe) trip people out, give them seizures, or send them over the bridge to Valhalla – always the Corpse Bridesmaid, never Morticia, the Bride of Gomez Addams.

            It’s amazing some guy in Neuchatel, Switzerland hasn’t put his family recipe for absinthe up for consideration as a treatment for Covid 19. You might not actually get over the infection, but you might not notice it…

          2. aairfccha says:

            @loupgarous – Good absinthe contained fairly little thujone, even pre-ban. In contrast, the bad stuff was a bit of anything goes, apparently including copper sulphate for coloring.

    2. Sad Screener says:

      Yes. Yes, a thousand times.

    3. Derek Lowe says:

      Yeah, thus the references to “shotguns” and “blunderbusses”. Not a very encouraging list, overall.

    4. Alan Jacobson says:

      I believe they should try Advair.

  3. mik says:

    quercetin ?

      1. anon the II says:

        No, just no.

        1. Lane Simonian says:

          Not so definitive:

          https://www.mcgill.ca/oss/article/health/quercetin-take-or-not-take

          If quercetin block or inhibits viral entry into cells it would seem better suited as a potential prevention measure. In that case, the antioxidant nature of polyphenols is irrelevant. On the other hand, if you can substantial break the cycle of oxidation–inflammation–oxidation–inflammation then perhaps certain polyphenols have a role in the treatment of various viral infections.

          1. John Smith says:

            Summit, IBM’s supercomputer ranks quercetin and luteolin high among small molecule candidates that bind to the coronavirus S-protein spikes so it cannot attach to the host cell. There are propolis nasal sprays. If I had respiratory symptoms, I think I would use it as an inhaler.

    1. Smcb says:

      I’m no scientist. And I’ve not Been tested for covert 19. But I did have symptoms which are indicative of it, and I took quercetin, which eradicated progressing joint pain but not the more troublesome hardening of mucus. So it’s usefulness may be limited.

  4. Disulfarim (at least in the test tube), is a very potent antiprotozoal. I had a post-grad student who looked at its effect on Entamoeba, Giardia and Trichomonas. All are highly dependent on cysteine proteases for survival. Years ago, don’t recollect the LD50 but it was pretty low.

    Interesting to these other antiprotozoals coming up as putative COVID-19 treatments. Wonder if any of the many compounds I tested against metronidazole-resistant trichomonads also had antiviral properties?

    1. S. Bress says:

      I have been confined & in close contact with my husband who was sick for days the first week of March then finally tested for covid-19 & received a positive result 7 days later. Interestingly- I’m immune suppressed with RA I am on methotrexate and Simponi aria biologic and in an 11 month flare. I finished a round of flagyl &doxycycline & monurol glandular for ongoing BV/ecoli & uti infections February24 . I AM STILL EITHER ASYMPTOMATIC OR VIRUS FREE. I’m so curious if it’s due to my medications. Would love some thoughts & feedback.

      1. Dafydd says:

        I have read that doxycycline is an Inhibitor of protein synthesis block inflammation and viral replication. They are looking in europe at the use of doxycycline as a potential prophylaxis treatment for COVID-19. Its very intersting that you were using this medication.

  5. heteromeles says:

    Re: Disulfiram. Great, now everyone will be chowing down on every inky cap mushroom (Coprinopsis atramentaria) that they can find. Expect a wave of mushroom poisoning cases to hit the ER too. (/facepalm)

    1. Even worse, they will have to queue behind the chloroquine overdose cases waiting for attention.

      Less flippantly, Europe seeing the hydroxychloroquine shortages seen in the States.
      https://www.theguardian.com/world/2020/mar/27/vital-drug-people-lupus-coronavirus-covid-19-link-hydroxychloroquine

    1. Derek Lowe says:

      That one is mentioned briefly in an earlier post (https://blogs.sciencemag.org/pipeline/archives/2020/03/06/covid-19-small-molecule-therapies-reviewed). I’ll be updating as more data come in, though.

  6. Alan Goldhammer says:

    There is a registered trial for camostat mesylate in Denmark. It has not started recruiting. Here is the NIH trial number: NCT04321096

  7. Toni says:

    Disulfiram is part of the CUSP9 trial in glioblastoma in Germany.
    The “deworming” drug Niclosamide (as well as some antiparasitic benzimidazoles) is also being investigated as a cancer drug (Nikolo trial).

  8. drsnowboard says:

    This is a list of zombie compounds. Nitazoxonide was trialled against HCV , absolutely useless. Niclosamide, c’mon man…

    I understand there’s a pandemic, but throwing dodgy mechanism compounds at a bunch of patients? I understand a uM cpd by some means might be effective at a certain time point in disease progression, but these are just dogs.

    1. Kevin says:

      I’ve been through the Niclosamide cycle with academic labs four times now. It has always gone like this:

      1. Lab discovers Niclosamide works in the cell-based assay. EC50 is in the 0.1 – 10 uM range
      2. Lab sees “hint of activity” in phenotypic animal model pushing heroic amounts into the animals
      3. Optimization to improve horrible bio-availability while keeping cell activity sucks down medicinal chemistry effort to find a new analog
      4. Dosing the new analog in PK at sub-therapeutic levels kills all the animals
      5. Invent ‘new hypothesis’ explaining toxicity
      6. Repeat steps 3-5 until all resources and credibility are exhausted

      1. HMehta says:

        Hi Kevin,

        I’d love to understand your experience here. I am an angel investor looking at Niclosamide.

        1. Kevin says:

          My contact info is linked my name.

          It is essential to know niclosamide’s molecular mechanism of action, the PK/PD, and why increasing systemic exposure in the host is a bad idea.

          1. Ruud van Ballegooijen says:

            https://news.utexas.edu/2020/04/06/new-delivery-method-could-make-niclosamide-an-effective-antiviral-to-treat-covid-19/

            University of Austin Texas has developed nanoformulated freezedried NCL powder.

            https://youtu.be/YPzaVW4BrIE

            Cancer industry will be on stand by with a big bag of cash, like they use to do, whenever someone’s touching NCL.

        2. Ruud van Ballegooijen says:

          https://phys.org/news/2020-05-nanomaterial-significantly-potential-covid-therapy.amp

          University of Purdue is looking for partners for distributor of Niclosamide/OHPP

          Purdue University scientist Yuan Yao’s laboratory has developed a solution, a plant-based, highly potent nanoparticle called OHPP (octenylsuccinate hydroxypropyl phytoglycogen) that can solubilize and enable niclosamide. Niclosamide’s solubility can be increased more than 5,000 times with OHPP, and the drug is effectively released to cells. Those findings were published in the International Journal of Pharmaceutics in 2018.

  9. FredB says:

    Quinine?

    1. In Vivo Veritas says:

      I’m self-doing as frequently as possible, starting at 4PM each day….. I’m still virus free!

  10. No more rules says:

    so much for being “drug-like”…. not having nitro groups…

    1. Klaus Witte says:

      Re.: aciclovir, famiciclovir
      Unfortunately, these compounds are far from being “general use antivirals”. They are converted into their active metabolites by thymidine kinase of herpes group viruses, which explains their lack of activity against most other virus groups.

      1. milkshake says:

        yes yes, the first phosphorylation to monophosphate is the hurdle indeed. Hence the complicated prodrug-protected phosphonate or phosphate in many Gilead drugs

  11. Asking for a friend says:

    Do general use antivirals such as aciclovir or famciclovir slow down coronavirus growth? In other words, would they have any use taken prophylactively to help lessen the severity of an infection?

    1. eyesoars says:

      Gor! Another way to go blind (like chloroquine).

  12. Paul says:

    “Known Drugs Against the Coronovirus: Runner-Up Candidates”

    Is “coronovirus” an alternate spelling of “coronavirus”? In any case, you use “SARS coronavirus” so it would be inconsistent nevertheless. Also, the phrasing of the title sounds like there are already effective drug therapies against COVID-19, which I believe a certain president is absurdly hoping for despite its distinct lack of existence. Perhaps “Known Drugs vs. the Coronavirus: Runner-Up Candidates”?

    Regardless, thank you for the excellent article. Always a pleasure to read your posts.

  13. Stanislav Radl says:

    As far as I know, disulfiram is metabolized to diethyldithiocarbamate, that chelates bivalent metals. Its anticancer activity is believed to be caused by formation of the corresponding Cu chelate (doi:10.1038/nature25016). Since chloroquine is known to be a ionophore for zinc, can disulfiram have similar function?

    1. ANON says:

      That was my first thought- it is a zinc sponge

  14. Freight says:

    I’m reminded of the line from Star Trek The Voyage Home……” My God Man, Drilling holes in the head isn’t the answer, the artery must be repaired”. Drugs can’t do all that much…they are throwing in a wrench and hoping for the best. Sure, some tweaking that may last for sometime, but nothing of cure-level capacity.

  15. Daniel Jones says:

    Derek? The news is latching onto how R & D is run for things as vital as COVID-19 treatment research and I thought I better pass along a link to one. You’re probably gonna have to address this, I fear.

    https://www.nationalmemo.com/we-already-paid-for-gileads-covid-19-treatment-and-shouldnt-pay-again/

    Did it already get paid for? Seriously. You know how the lab structures go; walk us through it.

    1. loupgarous says:

      The National Memo is Zero Hedge and Breitbart for the Far Left. That article repeats a canard Derek’s covered before about “who pays for drug development”.

    2. loupgarous says:

      If you’re looking for a non-industry involved discussion of drug development funding, try “The National Institutes of Health (NIH):
      Background and Congressional Issues”
      by the Congressional Research Service, starting at page 37, “Balancing Federal and Industry Support of Research”, which is a dispassionate discussion of the varying roles of academic and corporate research in drug development. I’ll let Derek do the explaining and interpretation, but suffice it to say, The National Memo was rabble rousing in their discussion of drug development (although they had a valid point that Derek’s also made about abuses of the orphan drug designation and associated benefits to Big Pharma).

  16. wubbles says:

    I’ve seen discussion that hyaluronic acid is being excreted into the airways as part of the inflammation response and results in the thick jelly characteristic of COVID-19 (source https://www.nature.com/articles/s41418-020-0530-3). The article wonders if hyaluronases would reduce the viscosity of the lung filler, and increase clearance and O2 transport.

  17. Dr. J says:

    It should be noted that nitazoxonide is a prodrug that has to be de-acetylated in vivo to produce the active drug substance (a phenol). So it would make sense that in vitro screens would not find it active (unless they are whole cell assays).

  18. Aren says:

    Several patients on long-term antibiotics report not getting sick from coronavirus, despite known exposure. Drugs reported include atovaquone (antimalarial), valproate (zinc ionophore), cefixime (antibiotic), and cefuroxime (antibiotic).

    https://www.healingwell.com/community/default.aspx?f=30&m=4185198&p=013

    1. Andro says:

      My doctor just prescribed me a long term antibiotic that is not really an antibiotic, I am told, called “Sulfamethoxazole Trimethoprim”. I have delayed starting to take it in the middle of the coronavirus crisis for fear it may be no good (and besides I am not suffering now strangely). Reading this, maybe I should start the treatment after all?

      1. Richard says:

        That’s Bactrim DS. Its used for bacteria and parasites like Malaria so wouldn’t surprise me if it was effective on COV

  19. M says:

    I was on Disulfiram for Lyme for two months. During that time I slept over 20 hours a day, and averaged about 500-750 calories a day). I dropped 10% of my body weight each month. Eventually I had to stop it as it was worse than the disease.

  20. Lane Simonian says:

    This one may have been posted before, but if not it is a review of potential treatments for the coronavirus.

    https://onlinelibrary.wiley.com/doi/10.1002/jmv.25707

  21. Mike Messagie says:

    Why are we even talking about this when HydroxyChloroquine has been succesful in Belgium, Bahrain, and South Korea.

    Make a billion pills and give everyone 10 pills.

    1. drsnowboard says:

      citation needed. NOT Twitter, NOT Reddit, NOT a newspaper article , you know , like evidence.

    2. loupgarous says:

      Don’t forget to add in funeral money for the people who shouldn’t be getting chloroquine or hydroxychloroquine, if they have pre-existing heart problems which late stage COVID-19 may make worse. No one makes money on clinical studies. They are done to prevent the thousands of deaths which occurred before we learned to watch what powerful and toxic drugs do in the human body carefully before handing them out like Skittles.

  22. Marya Lieberman says:

    Has anyone done an epidemiological study to see if people with lupus or rheumatoid arthritis (and who are already taking hydroxychloroquine) are less likely to acquire the COVID-19 virus or less likely to wind up with severe cases?

  23. Tafani says:

    Why not try to find a common feature from a pharmacodynamic stand point ?
    As:
    1) No magic treatment is likely to come from oldies but goodies, no matter how the DDbank is squeezed by curious PhDs, thus why not concentrate on a matrix type approach with PK/pD data, and patient screen: Disease onset, disease aggravation, disease complications?
    2) sars-cov2 has a rather well described target.s, intracellular biochem and a vastly unknown yet to understand extracellular signaling pathway in the late stages at least.
    3) outsiders -i.e; people focussing at almost expired patented drugs should avoid big pharma focus (protease inhib, statins, HTA with proton ATPase dep mode of action) BUT thinkink of eventual booster effect of any of those, including immunomodulators as IL2-o 6, IFNB or G while keeping an eye upon ADC, CD, midazolam potential negative interactions

    1. VicB says:

      I use NasalCrom for allergies. It is cromolyn sodium. Why isn’t cromolyn an option for ARDs?

        1. loupgarous says:

          should have read “A recent review of the medical literature on drugs for ARDS shows no consensus in published studies of beta blockers for ARDS on whether they are associated with increased or lowered death rate from ARDS.

  24. G Marquez says:

    Not a known drug, but promising is the anti-C5a monoclonal (InflaRx) under evaluation in China. Good rational for use and interesting case reports on preprint.
    https://www.medrxiv.org/content/10.1101/2020.03.29.20041962v1.full.pdf

  25. Zemyla says:

    Has anyone tried partial fluid ventilation with perfluorocarbons as a palliative measure, to help keep the lungs free of gorp?

    1. loupgarous says:

      Perflubron (Alliance’s perfluorohydrocarbon in fast-track FDA trials) has been tried in ARDS (the thing that claims those who die of COVID-19), but trials were discontinued when it was shown not to be more effective than the standard of care in ARDS, high-pressure oscillating ventilation.

  26. Tom says:

    Anyone know of followup to this research on indomethacin as an anti-viral?

    https://www.ncbi.nlm.nih.gov/pubmed/17302372
    If you can look past the side effects.
    Works fast and effectively for gout anyway.

    1. Erguen says:

      Just this preprint of in vitro and in vivo, which does not seem to have progressed towards print, or had any followup developments:
      “Indomethacin has a potent antiviral activity against SARS CoV-2 in vitro and canine coronavirus in vivo”. Tianhong Xu et al.
      http://biorxiv.org/content/10.1101/2020.04.01.017624v1

  27. bill says:

    i really think niclosamide should be trialed

  28. Dan S says:

    Anecdotal evidence but pretty compelling for Ciclesonide (Alvesco).
    https://writening.net/page?FC3QPm

  29. Dafydd says:

    I have read that the furin enzyme which is present in quantity in the lungs is the way the coronavirus gains access to cells. I have also read that curcumin which is present in Turmeric has strong ant viral properties and is able to block the furin pathway for covid-19.
    I for one have now started taking the highest strength bio active turmeric supplement I could find. Has this been tested on covid-19 patients.

  30. Dafydd says:

    I have also read that Cetylpyridinium Chloride (CPC) Exhibits Potent, Rapid Activity Against Influenza Viruses in vitro and in vivo. This is present in some mouthwashes namely Colgate Plax and various throat medicines such as Envil and Sepatbene throat sprays and lozenges . Has this been trial to protect health workers from viral load since the mode of entry is via the nose and throat.

  31. Dafydd says:

    That’s Septabene

  32. Dafydd says:

    CPC disrups the fatty envelope of enveloped viruses such as the coronavirus the CPC has a virucidal effect within 10 minutes of use. This effect is present even at very low doses of CPC.

  33. Juha says:

    Harvard cell scientist David Sinclairs protocol for protecting yourself
    Listen to the podcast.. Link below

    Keep your vitamin D levels up
    Intermittent fast
    Keep your blood sugar levels low by avoiding sugary foods
    Quercetin (500-600 mg, 1-2x a day)
    Research indicates quercetin inhibits viral replication
    Liposomal vitamin C (500 mg/day)
    Alpha-lipoic acid (ALA) (0.5-1 g, 1-2x a day)
    Data indicates ALA is helpful in fighting viral infections
    Zinc (40 mg/day)

    https://podcastnotes.org/bulletproof-radio/david-sinclair-covid-19-supplements-immune-system/

  34. Dafydd says:

    Ginkgo Biloba contains Quercetin and kaempferol which are able to block the pathway of covid-19 . I am taking that with the Turmeric.

  35. Newtotry2020 says:

    NCT04330586, KUMC-COVID-19, A Trial of Ciclesonide in Adults With Mild COVID-19 has similar trial been explored combining with 250 – 500 mcg Azithromycin (4 -5 days)?

  36. Anonymous says:

    Ivermectin (which has been discussed In The Pipeline in the past). I didn’t see it mentioned on any the previous lists of small molecules for COVID-19. It has now been shown to inhibit SARS-CoV-2 replication in vitro. Link to preprint in my handle. The article went on-line on April 3 (yesterday).

    “Ivermectin is an inhibitor of the COVID-19 causative virus (SARS-CoV-2) in vitro.
    A single treatment able to effect ∼5000-fold reduction in virus at 48h in cell culture.”

    It has already hit major news media and the wikipedia page on ivermectin.

  37. Walter Derzko says:

    Wrong Question. Wrong Answer
    Scientists should have asked the supercomputer: what molecules block viral replicase enzymes. Since spike proteins can change every season!

    Carbon 60 hydrated fullerenes, discovered in Ukraine as an antioxidant, is also a Universal antiviral, blocking several viral enzymes including replicase. It’s been on the market since 2010 as a dietary supplement, with no side effects and contraindications.

    Walter Derzko, Toronto

  38. Walter says:

    I am so happy to tell you this Robinson.buckler have a herbal cure to Herpes and you can take the medicine according to his instruction you will found out that you will give testimony like me I take his herbal medicine for just 2 week. I am so happy today that I am really free from this sickness here is Robinson.buckler email Robinson.buckler @{ yahoo. com }……………………………….

  39. Sanjosemike says:

    The “best” use of Disulfiram (another zinc Ionophore) allows Zn to be transferred into the cell, where it directly inhibits viral RNA transcription. Both Hydroxychloroquine and chloroquine are zinc ionophores. So you would combine a zinc ionophore with zinc. Zinc is definitely an “enemy” of viruses, of any kind. Zinc is generally well tolerated. So is Disulfiram.

    Zinc itself is very anti-viral. But it is most effective when “allowed” into the cell. A zinc ionophore like Disulfiram will do the same.

    BUT DON’T TAKE ANY ALCOHOL if you use this. You will have a violent reaction. You need to watch out for cough medicines. Many contain alcohol. So if you have Covid-19 and have a cough, do NOT use anything that has alcohol in it if you take Disulfiram.

    I do not give medical advice on line. Remember, just because I was a doctor does not mean I am correct.

    Sanjosemike (no longer in CA)
    retired surgeon

  40. Jeff says:

    I have moderately high blood pressure and take enalapril.it brings me down close to normal 130/80.is it safe for me to take querciten

  41. mark says:

    I’m asking as an amateur. niacinamide and hyaluronic acid, what is its effect on covid-19. Does it affect badly ?

  42. mark says:

    GABA can have a strong effect on covid-19

  43. Adli Karadsheh says:

    Regarding Cromolyn comment above, please read the letter I contributed a while ago. Cromolyn may be helpful.

    https://www.bmj.com/content/368/bmj.m1252/rr-1

    Regards

    1. Immunological mechanisms explaining the role of IgE, mast cells, histamine, elevating ferritin, IL-6, D-dimer, VEGF levels in COVID-19 and dengue, potential treatments such as mast cell stabilizers, antihistamines, Vitamin C, hydroxychloroquine, ivermectin and azithromycin
      https://doi.org/10.5281/zenodo.3748303

  44. Melody Galka says:

    My daughter is a PA on LongIsland. She has been hitting the disease hard and fast before a + result is received. Many of her patients have COVID symptoms test negative but when sent for an X-ray have COVID pneumonia. If her patients has COVID symptoms she follows a protocol with some variations based on her own research
    Metrodonazole
    Biaxin
    Singular
    Vit d
    Vit c
    Zinc
    Depending on symptoms has added Valtrex (Randesivier) and HAPE medication
    Overwhelming ALL her patients begin feeling better
    Also uses hydroxychloroquinine for + COVID patients ALL patients better

  45. nathan jones says:

    while I enjoyed the article I think that the simple and most effective solution are being overlooked. COVID is a respiratory disease, there are a number of papers out there that point out that upwards of 90% of the viral load is contained in the upper airway. if you want to give the patients the best chance of survival you need to knock out the viral nest, you do this by delivering an antiviral to the upper airway. The mucocilliary clearance cycle is roughly 4-5hrs so whatever antiviral you spray up your nose should be applied every 3-4hrs. There are groups at a number of universities where they are looking at possibilities, Stanford is looking at Iodine sprays, St. Andrews, Louisville, Pittsburgh, all are looking at options, and there are a umber of companies that are also looking at options.

    I do think that any real option is going to include xylitol for a number of reasons, it helps mask the terrible taste of most of these drugs, it helps break up biofilms, it works as a mucolytic to help thin out the mucous and in recent studies done at Utah State University it has been shown to kill the COVID19. All of these things combined make me think that we are appending way to much time and effort on a moonshot vaccine or IV drug to treat it after it has become a well intrenched disease. what we should be doing is spraying antivirals up the nose to give people a better chance to fight it on their own.

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