YK

A small trial finds that hydroxychloroquine is not effective for treating coronavirus

Recommended Posts

https://theconversation.com/a-small-trial-finds-that-hydroxychloroquine-is-not-effective-for-treating-coronavirus-135484

"...There are already other clinical studies that showed it is not effective against COVID-19 as well as several other viruses. And, more importantly, it can have dangerous side effects, as well as giving people false hope. The latter has led to widespread shortages of hydroxychloroquine for patients who need it to treat malaria, lupus and rheumatoid arthritis, the indications for which it was originally approved..."

  • Upvote 2

Share this post


Link to post
Share on other sites

26 minutes ago, Gerry Maddoux said:

^

Thanks for posting. Data--mostly anecdotal--should be leaking out by now about HCQ.

This virus is a very cunning little sucker!

A researcher has found that 2-deoxy-d-glucose will inhibit Covid replication in cells, even in such small doses in the cell culture medium that it is safe and doesn't kill the culture cells. A "prodrug" is being developed for that and shouldn't be very hard to manufacture.

2-deoxy-d-glucose is merely glucose that has a 2-hydroxyl group replaced by hydrogen, so it cannot undergo any further glycolysis but will competitively inhibit glucose-6-phospate synthesis for energy inside the cell. 

The answer may be something as simple as this: starve the virus, selectively, for glucose. Get the thesis: human cells are obviously replicating all the time but, in absence of cancer, at a constant rate. Whereas a massive infectious bolus of Covid-19, replicating furiously within respiratory tract epithelial cells, would eat up "fake sugar" preferentially. In other words, treat it like a malignantly replicating cancer cell with selective poisoning. 

Pretty novel idea. I hope it works. I'd sure like to see something simple and safe stop this devious little bastard!

 

If something stupid silly like xylitol helps with this I will be happy but laugh! "Chew gum."

I've read of similar "sugar starvation" mechanisms related to fungal and bacterial infections   In that case it was sort of stimulating the microbe to detach itself from a membrane binding site.  It sort of tricks them into "thinking" there is a meal available when in fact there is none.

  • Like 1
  • Upvote 1

Share this post


Link to post
Share on other sites

27 minutes ago, Enthalpic said:

f something stupid silly like xylitol helps with this I will be happy but laugh! "Chew gum."

I've read of similar "sugar starvation" mechanisms related to fungal and bacterial infections   In that case it was sort of stimulating the microbe to detach itself from a membrane binding site.  It sort of tricks them into "thinking" there is a meal available when in fact there is none.

HaHaHa, yeah, that would be a heck of a thing!

You probably know, there are several "fed" tumors. And those tumors can be "starved" a bit. 

This viral replication is apparently frenzied, so if any microorganism was susceptible, it would seem to be this one. 

  • Upvote 2

Share this post


Link to post
Share on other sites

1 hour ago, Gerry Maddoux said:

 

You probably know, there are several "fed" tumors. And those tumors can be "starved" a bit. 

 

I'm well aware.

For others, you can use radioactive isotopes of sugar to map metabolism

https://en.wikipedia.org/wiki/Positron_emission_tomography

  • Upvote 1

Share this post


Link to post
Share on other sites

2 hours ago, Gerry Maddoux said:

^

Thanks for posting. Data--mostly anecdotal--should be leaking out by now about HCQ.

This virus is a very cunning little sucker!

A researcher has found that 2-deoxy-d-glucose will inhibit Covid replication in cells, even in such small doses in the cell culture medium that it is safe and doesn't kill the culture cells. A "prodrug" is being developed for that and shouldn't be very hard to manufacture.

2-deoxy-d-glucose is merely glucose that has a 2-hydroxyl group replaced by hydrogen, so it cannot undergo any further glycolysis but will competitively inhibit glucose-6-phospate synthesis for energy inside the cell. 

The answer may be something as simple as this: starve the virus, selectively, for glucose. Get the thesis: human cells are obviously replicating all the time but, in absence of cancer, at a constant rate. Whereas a massive infectious bolus of Covid-19, replicating furiously within respiratory tract epithelial cells, would eat up "fake sugar" preferentially. In other words, treat it like a malignantly replicating cancer cell with selective poisoning. 

Pretty novel idea. I hope it works. I'd sure like to see something simple and safe stop this devious little bastard!

 

Need a translator in aisle 3!!!!!😂

  • Haha 1
  • Upvote 2

Share this post


Link to post
Share on other sites

35 minutes ago, Douglas Buckland said:

Need a translator in aisle 3!!!!!😂

Sorry that I didn't clean it up. To tell you the truth, I've forgotten more chemistry than I've retained but when glucose enters a cell it is either managed by glycolysis--running the sugar through about a ten-step enzyme process to convert it to eventual energy in the form of ATP (adenoside triphosphate)--or, if there is too much blood glucose lying around, converting it to glycogen, which is stored in skeletal muscle and the liver for later use. 

Think of 2-deoxy-d-glucose as "fake sugar." It throws a monkey wrench in the glycolytic pathway. So, in this case, while it would poison a certain number of human cells too, the much more rapidly replicating viruses would take up 2-deoxy-d-glucose voraciously and it would stop energy production by the virus (the glycolytic pathway would cease). 

It's so simple it's really a beautiful concept. It would only work for a very aggressively replicating virus, and this one seems to fit the bill. 

Now this "prodrug" these people are trying to make as a result from this observation? Your guess is as good as mine. It is of note, however, that while the viruses scare the bejiggers out of us (for good reason), they really are the simplest of organisms. They have nothing but either DNA or RNA inside a fatty capsid, in this case outfitted with stubby projections that are covered with glycans--another complex sugar--for defense and also for gaining entry into a cell. When they get in, they basically hijack all the host cellular machinery they need, without asking permission, in order to make us very sick, frequently enough to die. 

ORO is right when he repeatedly says that attempts to make messenger RNA vaccines have failed, because then we're vaccinating against, well, ourselves--and you think that won't produce an immunologic storm! So, the virus gurus are always looking for ways to shut down the little bastards without killing off the host. I was immediately struck by how novel this might be in killing off a novel virus--fitting in a poetic way.

  • Like 1
  • Great Response! 1
  • Upvote 6

Share this post


Link to post
Share on other sites

The purported mechanisms for the operation of HCQ/z is not an immune mechanism aimed at the virus. It makes no difference to the immune attack on the virus.

It does throw nits into the process of virus propagation in cell attachment and its metabolism and its replication in the cell (azithromycin's part). 

The virus is built to eat hemoglobin as well as replicate within lung epithelial cells. That is how it survives in the blood stream and arms itself with porphyrin which is the main attack medium on the lung cells, rather than the ACE2 receptors, which the researchers believe has only a weak interaction with the viral S spike protein, so must use the porphyrin to attach to the cell while transmitting through the ACE2.

The idea for antimalarial drugs (they bind to free heme) is to have them block the virus from stealing the porphyrin dissociated from the hemoglobin. That inhibits virus entry into cells, but not replication of the virus in the lung cells, it inhibits the spread of the virus through the blood stream, prevents heme poisoning, and relieves low oxygenation problems and protects the remaining hemoglobin. The azythromycin slows replication of the virus in the cell, as it trips up the RNA replication, same is it does for bacteria. 

I am pretty sure something better could be done to specifically block this action more thoroughly, but that will take a while, and this combo does work well. 

Hopefully I didn't butcher this.

The source is a couple of Chinese engineers, biomolecular (chem E) and computer scientist who model viral and cell molecules.

Abstract

The novel coronavirus pneumonia (COVID-19) is an infectious acute respiratory infection caused by the novel coronavirus. The virus is a positive-strand RNA virus with high homology to bat coronavirus. In this study, conserved domain analysis, homology modeling, and molecular docking were used to compare the biological roles of certain proteins of the novel coronavirus. The results showed the ORF8 and surface glycoprotein could bind to the porphyrin, respectively. At the same time, orf1ab, ORF10, and ORF3a proteins could coordinate attack the heme on the 1-beta chain of hemoglobin to dissociate the iron to form the porphyrin. The attack will cause less and less hemoglobin that can carry oxygen and carbon dioxide. The lung cells have extremely intense poisoning and inflammatory due to the inability to exchange carbon dioxide and oxygen frequently, which eventually results in ground-glass-like lung images. The mechanism also interfered with the normal heme anabolic pathway of the human body, is expected to result in human disease. According to the validation analysis of these finds, chloroquine could prevent orf1ab, ORF3a, and ORF10 to attack the heme to form the porphyrin, and inhibit the binding of ORF8 and surface glycoproteins to porphyrins to a certain extent, effectively relieve the symptoms of respiratory distress. Favipiravir could inhibit the envelope protein and ORF7a protein bind to porphyrin, prevent the virus from entering host cells, and catching free porphyrins. Because the novel coronavirus is dependent on porphyrins, it may originate from an ancient virus. Therefore, this research is of high value to contemporary biological experiments, disease prevention, and clinical treatmentAbstract The novel coronavirus pneumonia (COVID-19) is an infectious acute respiratory infection caused by the novel coronavirus. The virus is a positive-strand RNA virus with high homology to bat coronavirus. In this study, conserved domain analysis, homology modeling, and molecular docking were used to compare the biological roles of certain proteins of the novel coronavirus. The results showed the ORF8 and surface glycoprotein could bind to the porphyrin, respectively. At the same time, orf1ab, ORF10, and ORF3a proteins could coordinate attack the heme on the 1-beta chain of hemoglobin to dissociate the iron to form the porphyrin. The attack will cause less and less hemoglobin that can carry oxygen and carbon dioxide. The lung cells have extremely intense poisoning and inflammatory due to the inability to exchange carbon dioxide and oxygen frequently, which eventually results in ground-glass-like lung images. The mechanism also interfered with the normal heme anabolic pathway of the human body, is expected to result in human disease. According to the validation analysis of these finds, chloroquine could prevent orf1ab, ORF3a, and ORF10 to attack the heme to form the porphyrin, and inhibit the binding of ORF8 and surface glycoproteins to porphyrins to a certain extent, effectively relieve the symptoms of respiratory distress. Favipiravir could inhibit the envelope protein and ORF7a protein bind to porphyrin, prevent the virus from entering host cells, and catching free porphyrins. Because the novel coronavirus is dependent on porphyrins, it may originate from an ancient virus. Therefore, this research is of high value to contemporary biological experiments, disease prevention, and clinical treatment.

https://chemrxiv.org/articles/COVID-19_Disease_ORF8_and_Surface_Glycoprotein_Inhibit_Heme_Metabolism_by_Binding_to_Porphyrin/11938173

AI analysis of patient data predicts which patients are most likely to progress to ARDS and then die. Inflamatory conditions, high ALT and high hemoglobin levels before the disease progresses. Showing the correlation of the speed of virus propagation in the body with the available supply of porphyrin in hemoglobin.

https://www.sciencedaily.com/releases/2020/03/200330152135.htm

Hemoglobin levels drop for ICU patients during their stay with advanced COV 19 disease.

During their stay in ICU, those patients developed more profound, statistically significant decrements in their hemoglobin levels, with ALC and absolute monocyte count (AMC) levels compared to the non‐ICU group. The median nadir ALC was 0.4 × 109/L in the ICU group compared to 1.2 × 109/L in the non‐ICU group (P value <.001), while the median nadir AMC was 0.2 × 109/L in the ICU group, compared to 0.4 × 109/L in the non‐ICU group (P value <.001).

https://onlinelibrary.wiley.com/doi/10.1002/ajh.25774

 

In  short Yoshiro Kamamura, you should pick critical research that means something. Not a cherry picking of bad results from tiny trials. 

If you read the above carefully, you would know to expect that the HCQ/Z would not stop the progress of the disease in late stage patients who are already anemic, and have limited lung function due to damage. They would need additional treatment for the cytokine storm, to elevate their red blood cell counts, and support recovery from organ failure. A super potent targeted antiviral would not do any better either. 

Politically biased criticism of medicines is inexcusable. Shame on you.

HCQ/Z alone is intended for early and intermediate stage treatment. It can't solve the problems of end stage disease because that is no longer a matter the presence of the virus will affect and the viral population would be too large for this drug to have an effect at a tolerable dose. Perhaps it would be useful to adjust the dose to the initial viral count among the critical cases. But nobody has done so to date. For them, the terminal condition would over-ride potential side effects from an increased dose. 

From basic science - molecular structures, the treatment has potential. Clinically - in trials on early and mid stage disease, those taking HCQ/z had a more rapid decline in viral counts than those without, ending up virus free at 1-2 weeks earlier, and had fewer hospitalizations and ICU ventilations or deaths.

  • Great Response! 3
  • Upvote 3

Share this post


Link to post
Share on other sites

@Gerry Maddoux, I came across this hypothesis that death is potentially caused not by Acute Distress Syndrome, but by micro-thrombosis. Part of his reasoning is that people are seen collapsing from the virus (particularly in Iran) having not had previous respiratory distress - they were clearly able to walk to the store.

Again, no studies have been carried out on this, but it could suggest that anti-coagulants are important to reduce fatal clotting.  Full report here: http://farid.jalali.one/covid19emailpdf.pdf

image.thumb.png.f279cac5ef013b1784301eb650b40782.png

  • Like 1
  • Upvote 3

Share this post


Link to post
Share on other sites

6 hours ago, 0R0 said:

Hopefully I didn't butcher this.

No, you gave a very good explanation. I suspect that we're all going to be amazed at just how intricately this virus kills people. I already am. The thing is just so much more complicated with such a longer RNA strand than other coronaviruses! That in and of itself makes one immediately go to a nefarious explanation. 

Thanks to you and Geoff both for providing this new data. 

  • Like 3
  • Upvote 1

Share this post


Link to post
Share on other sites

7 hours ago, 0R0 said:

In  short Yoshiro Kamamura, you should pick critical research that means something. Not a cherry picking of bad results from tiny trials. 

 

Well, unlike you, I actually do. So far, there is only the original dubious French study whose metodology has been widely questioned, then there is one other study that comes to a conclusion that it "moderately alleviates mild cases", and then there is this study that finds it does not help at all. What you posted are some speculations - in medicine, you need a double blind study clearly proving efficacy of a cure to be recognized as such. Throwing random stuff at the patients and praying is not the scientific way. Trump is declaring HCL is the miracle cure, because he wants his buddies from Bayer to make good money - after all, he is their long time pal, he helped them in the past too:

https://www.wsj.com/articles/epa-backs-bayer-in-weedkiller-court-fight-11576879555

https://www.latimes.com/opinion/story/2020-04-06/rudy-giuliani-covid-19-coronavirus-hydroxychloroquine

The actual evidence, however, there is none. On the other hand, there are dangerous side-effects despite Trump's saying the drug "won't kill anyone", it actually can, plus it's definitely not a "gamechanger" - that's two Trump lies on the subject.

https://www.nbcnews.com/politics/donald-trump/mayo-clinic-cardiologist-inexcusable-ignore-hydroxychloroquine-side-effects-n1178776

https://www.forbes.com/sites/victoriaforster/2020/04/05/researchers-warn-that-covid-19-treatment-touted-by-trump-may-be-toxic-when-combined-with-diabetes-drug/#699e2b3b55f8

As it often is, there is no "miracle cure", no snake oil salesman will save us at the last minute. It's a new virus attacking the body with new methods, and to stop it, a new cure will probably have to be found. If it ever is found - there is still no cure for HIV after decades. 

  • Great Response! 1
  • Upvote 1

Share this post


Link to post
Share on other sites

5 hours ago, Geoff Guenther said:

@Gerry Maddoux, I came across this hypothesis that death is potentially caused not by Acute Distress Syndrome, but by micro-thrombosis. Part of his reasoning is that people are seen collapsing from the virus (particularly in Iran) having not had previous respiratory distress - they were clearly able to walk to the store.

Again, no studies have been carried out on this, but it could suggest that anti-coagulants are important to reduce fatal clotting.  Full report here: http://farid.jalali.one/covid19emailpdf.pdf

The way the virus kills is already researched and documented. It multiplies in the upper respiratory tract, forming sacs and deposits that are eventually breathed and washed into the lungs. At one moment, those sacs suddenly rupture, releasing large amounts of the virus at once, which throws the immune system into a panic mode and incited the cytokine storm. The cytokines battling the virus damage the lung tissue, and if their ability to supply oxygen decreases enough, organ damage and possible failure occurs, which is the cause of the death.

  • Great Response! 1

Share this post


Link to post
Share on other sites

Coronavirus: World leaders' posts deleted over fake news

https://www.bbc.com/news/technology-52106321

Facebook and Twitter have deleted posts from world leaders for spreading misinformation about the coronavirus.

Facebook deleted a video from Brazilian President Jair Bolsonaro that claimed hydroxychloroquine was totally effective in treating the virus.

He has repeatedly downplayed the virus and encouraged Brazilians to ignore medical advice on social distancing.

It follows Twitter’s deletion of a homemade treatment tweeted by Venezuelan President Nicolás Maduro.

Both social networks rarely interfere with messages from world leaders, even when they are verifiably untrue.

Twitter, for example, says it will “will err on the side of leaving the content up” when world leaders break the rules, citing the public interest.

But all major social networks are under pressure to combat misinformation surrounding the coronavirus pandemic.

  • Like 1
  • Upvote 2

Share this post


Link to post
Share on other sites

19 minutes ago, Yoshiro Kamamura said:

Well, unlike you, I actually do. So far, there is only the original dubious French study whose metodology has been widely questioned, then there is one other study that comes to a conclusion that it "moderately alleviates mild cases", and then there is this study that finds it does not help at all. What you posted are some speculations - in medicine, you need a double blind study clearly proving efficacy of a cure to be recognized as such. Throwing random stuff at the patients and praying is not the scientific way. Trump is declaring HCL is the miracle cure, because he wants his buddies from Bayer to make good money - after all, he is their long time pal, he helped them in the past too:

https://www.wsj.com/articles/epa-backs-bayer-in-weedkiller-court-fight-11576879555

https://www.latimes.com/opinion/story/2020-04-06/rudy-giuliani-covid-19-coronavirus-hydroxychloroquine

The actual evidence, however, there is none. On the other hand, there are dangerous side-effects despite Trump's saying the drug "won't kill anyone", it actually can, plus it's definitely not a "gamechanger" - that's two Trump lies on the subject.

https://www.nbcnews.com/politics/donald-trump/mayo-clinic-cardiologist-inexcusable-ignore-hydroxychloroquine-side-effects-n1178776

https://www.forbes.com/sites/victoriaforster/2020/04/05/researchers-warn-that-covid-19-treatment-touted-by-trump-may-be-toxic-when-combined-with-diabetes-drug/#699e2b3b55f8

As it often is, there is no "miracle cure", no snake oil salesman will save us at the last minute. It's a new virus attacking the body with new methods, and to stop it, a new cure will probably have to be found. If it ever is found - there is still no cure for HIV after decades. 

I get it Frank, er I mean Yoshi, you've got TDS and you've got it bad. No cure for that either, along with your AIDS. 

Bottom line the number one and best use of hydroxychloroquine is as a prophylactic. Recognize it was discovered that Lupus patients were apparently immune to the disease, as long as they had been on hydroxychloroquine or chloroquine regimens. To this day, it appears the lupus patients have yet to contract this virus. Put that in your wumao and smoke it. 

As for the danger of the medicine, the doctor with more patients and experience with hydroxychloroquine than anyone else is the US, with the largest lupus practice has never had a single patient hospitalized or sickened with the drug. But hey, what does he know compared to an NBC reporter? He's only been doing this for 42 years and the MSM DNC only heard of this drug 42 days ago! 

 

  • Upvote 2

Share this post


Link to post
Share on other sites

(edited)

51 minutes ago, Ward Smith said:

As for the danger of the medicine, the doctor with more patients and experience with hydroxychloroquine than anyone else is the US, with the largest lupus practice has never had a single patient hospitalized or sickened with the drug. But hey, what does he know compared to an NBC reporter? He's only been doing this for 42 years and the MSM DNC only heard of this drug 42 days ago! 

 

The potential problem is not the lupus expert who is experienced with the drug - there may be some problems with other naive physicians or people self-medicating.

Edited by Enthalpic
  • Upvote 1

Share this post


Link to post
Share on other sites

17 hours ago, Yoshiro Kamamura said:

https://theconversation.com/a-small-trial-finds-that-hydroxychloroquine-is-not-effective-for-treating-coronavirus-135484

"...There are already other clinical studies that showed it is not effective against COVID-19 as well as several other viruses. And, more importantly, it can have dangerous side effects, as well as giving people false hope. The latter has led to widespread shortages of hydroxychloroquine for patients who need it to treat malaria, lupus and rheumatoid arthritis, the indications for which it was originally approved..."

Ok, we will make sure that you and Geoff don't get treated with it!

  • Haha 1

Share this post


Link to post
Share on other sites

15 hours ago, Gerry Maddoux said:

^

Thanks for posting. Data--mostly anecdotal--should be leaking out by now about HCQ.

This virus is a very cunning little sucker!

A researcher has found that 2-deoxy-d-glucose will inhibit Covid replication in cells, even in such small doses in the cell culture medium that it is safe and doesn't kill the culture cells. A "prodrug" is being developed for that and shouldn't be very hard to manufacture.

2-deoxy-d-glucose is merely glucose that has a 2-hydroxyl group replaced by hydrogen, so it cannot undergo any further glycolysis but will competitively inhibit glucose-6-phospate synthesis for energy inside the cell. 

The answer may be something as simple as this: starve the virus, selectively, for glucose. Get the thesis: human cells are obviously replicating all the time but, in absence of cancer, at a constant rate. Whereas a massive infectious bolus of Covid-19, replicating furiously within respiratory tract epithelial cells, would eat up "fake sugar" preferentially. In other words, treat it like a malignantly replicating cancer cell with selective poisoning. 

Pretty novel idea. I hope it works. I'd sure like to see something simple and safe stop this devious little bastard!

 

OK, so my normal diet contains lots of artificial sweeteners. I am now AOK? Sarcasm mixed with scant hope. 

  • Like 1
  • Haha 2
  • Upvote 2

Share this post


Link to post
Share on other sites

14 hours ago, Gerry Maddoux said:

HaHaHa, yeah, that would be a heck of a thing!

You probably know, there are several "fed" tumors. And those tumors can be "starved" a bit. 

This viral replication is apparently frenzied, so if any microorganism was susceptible, it would seem to be this one. 

I have heard that fasting is helpful with some illnesses. Do you have any thoughts about that especially as related to covid 19?

Share this post


Link to post
Share on other sites

5 minutes ago, ronwagn said:

I have heard that fasting is helpful with some illnesses. Do you have any thoughts about that especially as related to covid 19?

Going Keto on covid haha

  • Haha 1

Share this post


Link to post
Share on other sites

(edited)

Joke - maybe... "starve a fever"

Edited by Enthalpic
  • Haha 1

Share this post


Link to post
Share on other sites

1 hour ago, ronwagn said:

I have heard that fasting is helpful with some illnesses. Do you have any thoughts about that especially as related to covid 19?

I doubt it, Ron. Maybe if you went at it long enough to become truly catabolic. But at some point you'd suppress the immune system. 

  • Like 1
  • Upvote 2

Share this post


Link to post
Share on other sites

Kamamura

Your posting would be disgustingly repugnant but for the fact it offers a clear display of the rampant deceit so widely exposed these days.

Your (first) linked post references 2 'studies' ... the first being the Chinese one that DID NOT INCLUDE zinc!!!.

ALL the subsequent medical contributions stress the importance of including zinc ... preferentially as Z pack and sulfate.

The SECOND, FRENCH STUDY ???!!! from Molina???

Did you read it?

Did anyone here even read the highlights????

11 patients ... 8  with underlying health conditions, 10 with  fever and QUITE  ILL!!!

 

Of the original 11??? 

One (by inference only, as it is NOT depicted in your linked article), showed NO virus present ... 1 died, 2 to ICU ... 1 removed from study ... 

So, Kamamura, your OWN article describes SEVEN (out of the original 11) no longer being "quite ill" (!!!) if non ICU intervention is the threshold.

Complications from hydroxychloroquine use???

How about the 42 year long career of Dr. Daniel Wallace, the USA's leading lupus practitioner out of Los Angeles who has NEVER (his words) observed negative side effects in the THOUSANDS of patients to whom he has prescribed hydroxychloroquine?

And you motherfuckers wonder why the rage is slowly consolidating on a global scale in the presence of this purposeful malevolence?

  • Great Response! 1
  • Upvote 2

Share this post


Link to post
Share on other sites

Join the conversation

You can post now and register later. If you have an account, sign in now to post with your account.

Guest
You are posting as a guest. If you have an account, please sign in.
Reply to this topic...

×   Pasted as rich text.   Paste as plain text instead

  Only 75 emoji are allowed.

×   Your link has been automatically embedded.   Display as a link instead

×   Your previous content has been restored.   Clear editor

×   You cannot paste images directly. Upload or insert images from URL.