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Azithromycin (HCQ’s sidekick) is apparently far more than an antibiotic

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There is a report that Azithromycin is far more than an antibiotic. Some may wish to watch an interview with Dr. Michael Lisanti on antibiotics for COVID-19 and cancer. But — without endorsing as “proved” fact — let’s cut to the chase scene:

COVID-19 coronavirus is particularly dangerous for the elderly or those with aging-related senescent illnesses like diabetes, cancer, heart disease, and lung disease. As Professor Lisanti said in a statement on his new paper in the journal Aging, “If you look at the host receptors of COVID-19, they are related to senescence. Two proteins have been proposed to be the cellular receptors of COVID-19: one is CD26 – a marker of senescence, and the other, ACE-2, is also associated with senescence. So, older people would be predicted to be more susceptible to COVID-19, exactly as is observed clinically in patients. This could increase their probability of infection, and would explain the increased fatality of COVID-19 infection in older patients. All of this could be related to advanced chronological age and senescent cells.”

Lisanti’s laboratory has previously demonstrated that Z-pak [a version of Azithromycin] selectively removes 97% of senescent cells. Without those cells acting as host receptors, it may be harder for COVID-19 to take root in the body and cause serious damage.

Lisanti’s lab goes on, “Clinically, it appears what is leading to fatalities in older [COVID-19] patients is the very strong inflammatory reaction and the resulting fibrosis. Azithromycin inhibits inflammation-induced fibrosis, by targeting and removing senescent cells. The cost would be minimal, as the drug is off-patent, widely available and considered safe.”

Z-pak has made headlines after doctors around the world such as the widely publicized French clinic trials and New York and New Jersey physicians have found promising results on the front-lines of coronavirus using it in combination with another generic drug hydroxychloroquine . . . .

But, but, but, doesn’t an antibiotic work against Bacteria? Yes, the issue is HOW, and whether the cluster of effects of a given drug may also be effective against the viral replication-by-hijacking cycle.

A hypothesis is posed:

In the paper, we also find:

Recently, a clinical trial was conducted using COVID-19 positive hospitalized patients, which assessed COVID-19 virus production in response to treatment with two FDA-approved drugs, namely Hydroxy-chloroquine (Plaquenil) and Azithromycin (Z-PAC) [13]. Hydroxy-chloroquine alone, at the standard dosages, was surprisingly effective in reducing COVID-19 viral production. However, the combination of Hydroxy-chloroquine and Azithromycin appeared to be even more effective. The mechanism(s) by which this drug combination halts COVID-19 virus production remains unknown . . . . Chloroquine and its derivatives, such as Hydroxy-chloroquine, alkalinize the pH in lysosomes, which accumulate in large numbers in senescent cells. This Chloroquine-induced alkalinization functionally prevents the induction and accumulation of one of the most widely-recognized markers of senescence, known as beta-galactosidase (Beta-Gal), a lysosomal enzyme [14]. Hydroxy-chloroquine is also used clinically for the treatment of chronic inflammatory diseases, such as Sjögren’s syndrome, and it effectively reduces the salivary and serum levels of IL-6, a key component of the SASP [15].

This of course is a suggested mechanism that may well be working in parallel with the Zn ionophore effect.

That rather reminds me of the Allied shock of finding the Germans using an anti-aircraft gun in the anti-tank and bunker-busting role, the infamous 88-mm gun originally developed by the Krupp concern. Soon it had mutated into a whole family of guns, especially in the notorious Tiger tank family. By contrast, it was after the war that the British were able to fully develop the 20 pounder, which IIRC, was at least influenced by the UK 3.7 inch AA gun, which was far heavier than the German 88. (Mind you, in North Africa, they diverted the 25 pounder Gun-Howitzer to the antitank role, a calibre 87.6 mm weapon derived from the earlier 18 pounder and also replacing the 4.5 inch howitzer as a standard field gun.)

In short, flexibility is a relevant and potentially decisive matter.

The same article puts some further food for thought on the table:

New drugs cost a billion dollars and 10-15 years to make it through the FDA approval process. This regulatory hurdle precludes natural substances that cannot be patented from being properly researched and tested for illnesses because companies cannot afford the cost to prove the efficacy of something that any organization would be able to sell afterwards. This top-down monopoly approach to medicine can leave the world on its heels—not enough clinical trials on natural substances and patent-dependent, new FDA-d drugs and vaccines years away—during a pandemic like the one we are in now.

Some, would suggest, that’s not a bug, it’s a feature.

We need to be asking some very pointed questions about drug development, trials and strategies for an emerging age of pandemics. END

21 Replies to “Azithromycin (HCQ’s sidekick) is apparently far more than an antibiotic

  1. 1
    kairosfocus says:

    Azithromycin (HCQ’s sidekick) is apparently far more than an antibiotic

    — Dr. Michael Lisanti suggests that “If you look at the host receptors of COVID-19, they are related to senescence. Two proteins have been proposed to be the cellular receptors of COVID-19: one is CD26 – a marker of senescence, and the other, ACE-2, is also associated with senescence. So, older people would be predicted to be more susceptible to COVID-19, exactly as is observed clinically in patients . . . . Z-pak [a version of Azithromycin] selectively removes 97% of senescent cells. Without those cells acting as host receptors, it may be harder for COVID-19 to take root in the body and cause serious damage . . . . Azithromycin inhibits inflammation-induced fibrosis, by targeting and removing senescent cells”

    — So, we have a working model that suggests that Azithromycin could have two effects, suppressing secondary infection [acting as an antibiotic] and hitting cell types with receptors targetted by SARS2.

    –BTW, the main interest in those deteriorated cells is a suspicion that they are early precursors in the chain leading to cancer. Which, notoriously, is correlated with aging.

  2. 2
    kairosfocus says:

    Looks like we have some proposed possible multi-action mechanisms for both of the main ingredients in the cocktail. Where the ionophore mechanism makes sense of using Zn supplements.

  3. 3
  4. 4
    kairosfocus says:

    Isn’t it interesting to see what is not being responded to, when it is one of the most significant findings relevant to hopes for effective treatment.

  5. 5
    jerry says:

    Kf,

    latest video from MedCram is on blood clots. Haven’t looked at it yet since busy with other things. Probably about strokes too though haven’t watched it.

    https://www.youtube.com/watch?v=22Bn8jsGI54

  6. 6
    jerry says:

    Kf

    Dr. Seheult in Medcram video linked above talks about in detail what may be happening with the virus to cause these strokes. Apparently after attacking the lungs it attacks the blood cells and the ACE2 receptors there which causes the ACE2 from functioning properly and then causes the release of coagulants which cause clots. This is now causing things they never saw before. (Might not be accurately said by me)

    Which leads to what NY doctor said that they did not know what they were doing since they had never seen this before.

    Also says they administer HCQ, zinc and azithromycin to all but it sounds like they are not getting unusually good results. Again it is late in the disease when. they are getting to hospital and ICU.

  7. 7
    kairosfocus says:

    Jerry, it looks like a tradeoff issue with ACE type receptors. The circle is squared by getting the disease early on before it wreaks havoc, including through blood clotting and constriction of blood vessels. Again, pointing to early action. BTW, VDH here is raising wider policy questions https://www.youtube.com/watch?v=KqCudv-JQ2o KF

    PS: Meanwhile let us note from OP that Azithromycin seems to have more than just antibacterial action.

  8. 8
    Bob O'H says:

    Isn’t it interesting to see what is not being responded to, when it is one of the most significant findings relevant to hopes for effective treatment.

    Oh, sorry. I missed the discussion of a properly conducted clinical trial showing an effective treatment.

  9. 9
  10. 10
    jerry says:

    Oh, sorry. I missed the discussion of a properly conducted clinical trial showing an effective treatment.

    There is no doubt that it is effective if used early. Also there is no other treatment out there. All present C19 infected people are told the only way to cure this is to hope your immune system will do it. For most this will work but for a small percentage it will not. This small percentage adds up to several million dead if no treatment is found.

    Zelenko pointed out the concept of flattening the curve is not a life saving strategy. It is just a prolonging the time till people die so they currently do not overwhelm the hospital system. During this flattening the curve time, hundreds of millions are being put out of work world wide. The rationale is insane when analyzed correctly.

    What would be a real massive death sentence is to say it cannot be used till a clinical trial using traditional approaches is done. Most take several years and my guess several hundred thousand will die before a hurried one is done. But be as it may, some are currently being planned.

    As there is at present no alternative treatment to compare it to what is lost by using it.. This recommended approach includes extremely inexpensive drugs approved for children and pregnant women. Zelenko said it cost him $12 for the total treatment. To keep on suggesting a clinical. trial is needed is a death sentence to thousands. There is no credible reason to maintain this position.

  11. 11
    kairosfocus says:

    H, that is a baseline study on chemical effectiveness. 15+ years ago in a context of a need for broadly acting antivirals. KF

  12. 12
    Bob O'H says:

    Jerry @ 10 –

    There is no doubt that [HCQ] is effective if used early.

    You might not have any doubt, but I hope you’re aware that a lot of medical professionals do have doubts. And it’s their views that are going to matter.

    I’d hope it’s clear that the current evidence isn’t convincing, so what are you going to do to change minds?

  13. 13
    ET says:

    The current evidence says that HCQ along with zinc cures people. There are thousands of people alive today thanks to that therapy. The medical professionals that don’t understand the science shouldn’t be treating people with covid 19. That is the only thing that is clear.

  14. 14
    ET says:

    Bob O’H wants a clinical trial and Jerry offers real-world cases.

  15. 15
    jerry says:

    I hope you’re aware that a lot of medical professionals do have doubts.

    Oh I am very much aware of that. All I have seen though is opinions not analysis based on facts. The Wall Street Journal just published yesterday a new article on the “great minds” that have gotten together to help solve the problem. They trashed HCQ with nothing but opinion and bogus reporting on the VA study.

    HCQ and Azithromycin are the most used treatments in the world for the virus. About a quarter of world doctors surveyed are recommending HCQ as a prophylactic. My wife and I were given it as a prophylactic when we went to Africa 6 years ago.

    The most common treatment in the US is to do nothing. Over 50% of the US doctors responded as such. Zinc is only being used by a very small percentage of doctors in the world. Interesting the highest place is NY state as maybe Zelenko is having some effect. The head of Lennox Hill hospital is a colleague of Zelenko. And yes I know that NY metropolitan area is probably hardest hit in world. right up there with Lombardy.

  16. 16
    jerry says:

    Here is an article from Israel yesterday about South Korea’s response to the virus.

    Hydroxychloroquine used by Korea for Covid-19 while US is divided

    https://bit.ly/2VKEx2n

    So I am very much aware that doctors are divided especially in the US where it seems it is all about politics.

  17. 17
    Bob O'H says:

    Good, Jerry. So what’s your strategy for convincing sceptical doctors that HCQ (possibly plus AZ and Zn) is effective?

  18. 18
    jerry says:

    So what’s your strategy for convincing sceptical doctors that HCQ (possibly plus AZ and Zn) is effective?

    Me? I am here trying to gather evidence and my posts are meant to clarify my thoughts while learning from others. I have personally found it almost impossible to convince others to even look at the information. That is the most interesting personal finding so far. So I know how hard it is.

    But in the process of searching I have not found one rational objection here, on the internet or with close friends and relatives to using HCQ and zinc in early treatment. None! That is the most important empirical finding given the intense desire to disprove it by many.

    My personal friends usually say they have not seen it in the press or one good friend who said he didn’t like taking any drugs. Zinc is almost non existent in the US press. A couple friends laughed when I mentioned it as how could anything like that be effective.

    But others are raising the necessary points. As to control studies here is a post by a couple professionals at Harvard you might want to look at. They raise similar points that I and others have brought up.

    https://bit.ly/3bRxuuo

  19. 19
    kairosfocus says:

    BO’H, you used a key, revealing word, “sceptical.” This inadvertently speaks to how prudence as a balanced virtue has been largely displaced by selective hyperskepticism and want of sound understanding of inductive warrant. So, at one level we need to use the strategic decision making result I have been pointing to where a business as usual baseline and its reasonably expected or observed outcome can be compared to one or more reasonably plausible alternatives. So, we can do a gap analysis on the projections and motivate strategic change. Then, at level two we need to re-assess how a gold standard fallacy has been allowed to creep in and undermine ability to address a fast-moving pandemic. At the third level, under the radar, strong momentum is clearly building up. KF

  20. 20
    kairosfocus says:

    Jerry, Ms Lin’s article is excellent. KF

  21. 21
    kairosfocus says:

    PS: I clip:

    Hydroxychloroquine used by Korea for Covid-19 while US is divided
    Apr 27, 2020, 9:52 PM

    South Korea recommended the anti-malarial drug HCQ to treat Covid-19 while political interference in the US over the drug has alarmed medical experts

    [ . . . ]

    Medical treatments have traditionally been a private decision between patients and doctors, but now it seems politicians are usurping their right to choose. According to Dr Jeffrey Singer, a general surgeon and Cato Institute fellow, this threatens the integrity of the medical profession and indirectly imperils patients, by denying them emergency options when no other alternatives are available.

    Moreover, the politicization of treatment options would not help Americans, given the fact countries such as Belgium, France and South Korea have used HCQ to treat Covid-19 with a good degree of success.

    South Korea was one of the first countries to be hit by the virus after China, reporting its first case on January 20 and peaking by late February, before suddenly tapering off in early March and “flattening the curve.” It also has a comparatively low mortality rate through a combination of testing, tracing, containment and HCQ . . . .

    Hydroxychloroquine (HCQ), a well-known anti-malarial drug that has been around for decades, is now a political football between the Trump administration and Democrats during an election year in the United States.

    US President Donald Trump has repeatedly touted the drug and received significant pushback from the media and the Democratic Party, with the governors of Nevada, Michigan and New York even going so far as to issue executive orders restricting how doctors can use HCQ to treat patients suffering from Covid-19.

    Medical treatments have traditionally been a private decision between patients and doctors, but now it seems politicians are usurping their right to choose. According to Dr Jeffrey Singer, a general surgeon and Cato Institute fellow, this threatens the integrity of the medical profession and indirectly imperils patients, by denying them emergency options when no other alternatives are available.

    Moreover, the politicization of treatment options would not help Americans, given the fact countries such as Belgium, France and South Korea have used HCQ to treat Covid-19 with a good degree of success.

    South Korea was one of the first countries to be hit by the virus after China, reporting its first case on January 20 and peaking by late February, before suddenly tapering off in early March and “flattening the curve.” It also has a comparatively low mortality rate through a combination of testing, tracing, containment and HCQ.

    Last month, the Korea Centers for Disease Control and Prevention, the Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, Korean Society of Pediatric Infectious Diseases and a tuberculosis association recommended the use of Kaletra, an anti-HIV medication, in combination with HCQ, to treat Covid-19.

    This was bolstered by a French study that showed HCQ had an antiviral effect against Covid-19 in confirmed cases. Used in conjunction with the azithromycin Z-Pak, most patients cleared the virus in three to six days rather than the 20 days observed in China, drastically narrowing the period during which a patient can spread the virus to others.

    As such, Dr Jeff Colyer, chairman of the US National Advisory Commission on Rural Health, and Dr Daniel Hinthorn, director of the Division of Infectious Disease at the University of Kansas Medical Center, in a Wall Street Journal article recommended that the US could adopt this approach and use the treatment cocktail early rather than wait until a patient is on a ventilator in an intensive care unit.

    To be clear, these scientists and doctors now recommend HCQ as a treatment, not a preventive measure, for Covid-19. They argue that a positive effect of using HCQ early is the reduction of virus transmission to other people given the shorter number of days the patients remain contagious, thereby flattening the curve sooner.

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