3083 replies to this topic

[lancebr]

The havent got MasterJohns Vitamin D update censored yet.  About 4:15 to 5:10 he talks about whether the infection lowered D levels and claims that is a possibility.

 

At the end he recommends around 1000IU if you cant test(to reach 30ng/ml) with a maximum of 1700IU (thus the confusion from earlier posting).   Not sure if we could say anyone is more informed about it than him as far as taking advice.

 

https://www.youtube....h?v=738yuE5nDfg

 

Dr. Rhonda Patrick seems to be more informed about Vitamin D and its uses compared to Dr. Masterjohn.

 

There are many doctors and researchers who believe you have to have more than 1700 iu to reach the optimal level.

 

Here is a study showing that in healthy adults they need "a dose of 95 microg/d (3800 IU) for those above a 25(OH)D threshold

of 55 nmol/L (22 ng/ml) and a dose of 125 microg/d (5000 IU) for those below that threshold" required to attain serum 25(OH)D

concentrations >75 nmol/L (30 ng/ml).

 

https://www.ncbi.nlm...pubmed/18541590

 

 

Edited by lancebr, 01 May 2020 - 12:12 AM.

[lancebr]

This is interesting but I wonder if the vitamin D level could have dropped as a result of the patients having more severe illness. I followed the link but didn't see where this had been addressed or accounted for. Does this tend to happen in illness, or is the body good at maintaining a steady balance based on stored vitamin D?

 

I remember reading a paper a few weeks ago, trying to locate it, that stated that individuals who had

influenza or other type of infections had a decrease in vitamin D levels due to those infections.  It was

assumed that the body was using the vitamin D to help the immune system fight off the infection.

 

So if there is a reduction in D levels because of an infection then it might be assumes that Covid-19

would potentially cause a decrease in D levels since the body would be using it to fight off the infection.

 

So the following numbers in that one study showing that higher D levels had a better outcome makes you

wonder if those individuals had a much higher level of D in their system before they caught the virus.

 

 

"Among mild cases, it was, on average, 31.2; among ordinary cases, it was 27.4;

among severe cases, it was 21.2; among critical cases, it was 17.1."

 

So what if the mild cases had like a level in the range of 40s or 50s and the covid caused a reduction.

Then we might want to shoot for higher levels of D to have a safety net if the virus does cause a reduction.

 

[Daniel Cooper]

Epistemic authoritarianism.  According to the Youtube monopoly, the WHO decides what is true, and no one is permitted to publicly contest a truth decided by WHO.

 

John Stuart Mill:

 

Pretty much the situation we find ourselves in.  Open debate is no longer the feature of Western Civilization that it once was.

 

How on earth YouTube considers itself qualified to determine what is and is not "medical scientific truth" is beyond me.

[Gal220]

Dr. Rhonda Patrick seems to be more informed about Vitamin D and its uses compared to Dr. Masterjohn.

 

There are many doctors and researchers who believe you have to have more than 1700 iu to reach the optimal level.

 

Here is a study showing that in healthy adults they need "a dose of 95 microg/d (3800 IU) for those above a 25(OH)D threshold

of 55 nmol/L (22 ng/ml) and a dose of 125 microg/d (5000 IU) for those below that threshold" required to attain serum 25(OH)D

concentrations >75 nmol/L (30 ng/ml).

 

https://www.ncbi.nlm...pubmed/18541590

 

Hes informed about it, of that I have no doubt - https://drruscio.com...l-of-vitamin-d/ - he could still be wrong of course, and has adjusted his opinion based on new evidence.  Hard to fault that.

 

Andrew Weil is recommending taking 2000iu up until symptoms, then stopping.  Kessler like Masterjohn is recommending 1000IU.  They are all basing their opinions on how CoVid is known to work.  

 

However I will say I think they are all quite novices when it comes to presenting information, not unlike many websites though.

[Gal220]

Pretty much the situation we find ourselves in.  Open debate is no longer the feature of Western Civilization that it once was.

 

How on earth YouTube considers itself qualified to determine what is and is not "medical scientific truth" is beyond me.

 

I noticed Masterjohn gave the proverbial this isnt medical advice spiel real quick in his video, even though it obviously is...

[Florin]

"We found and tested 47 old drugs that might treat the coronavirus: Results show promising leads and a whole new way to fight COVID-19"
 
https://theconversat...covid-19-136789
https://www.nature.c...1586-020-2286-9

 
But wait, there's more! First, lets thrash HCQ a bit:

 

...hydroxychloroquine...also binds to the SigmaR1 and SigmaR2 receptors. But based on our experiments in both labs, we do not think hydroxychloroquine binds to them efficiently.
 
Because of these differences in binding tendencies, we don’t think hydroxychloroquine is a reliable treatment.

And then offer some hope:

 

We not only found multiple drugs that might fight SARS-CoV-2, we learned how and why.

But that is not the only thing to be excited about. These same proteins that SARS-CoV-2 uses to infect and replicate in human cells and that are targeted by these drugs are also hijacked by related coronaviruses SARS-1 and MERS. So if any of these drugs do work, they will likely be effective against COVID-22, COVID-24 or any future iterations of COVID that may emerge.

[Daniel Cooper]

 
But wait, there's more! First, lets thrash HCQ a bit:

 

And then offer some hope:

 

Perhaps this explains some of the differences in outcome of men vs. women in covid infections:

 

 

Two potent antihistamines, clemastine and cloperastine, also displayed antiviral activity, as did the compound PB28 and the female hormone progesterone.

[lancebr]

Hes informed about it, of that I have no doubt - https://drruscio.com...l-of-vitamin-d/ - he could still be wrong of course, and has adjusted his opinion based on new evidence.  Hard to fault that.

 

Andrew Weil is recommending taking 2000iu up until symptoms, then stopping.  Kessler like Masterjohn is recommending 1000IU.  They are all basing their opinions on how CoVid is known to work.  

 

However I will say I think they are all quite novices when it comes to presenting information, not unlike many websites though.

 

I guess this Dr. Bruce Hollis will have more knowledge about Vitamin D since he has studied it for 40 years.

 

He says that he takes 6,000 iu a day to keep his immune system strong and he recommends the average

adult to take between 4,000 and 6,000 iu daily.

 

He says it takes about 3 months of supplementation to create a steady level.

 

https://www.wbtw.com...d-19-be-linked/
 

[Dorian Grey]

Just saw an analysis of Fauci's remdesivir trial. They changed the parameters on the fly to get their desired result, enlarging the trial twice trying to reach statistical significance for mortality improvement. When that didn't work, they dropped mortality rate from a primary end point to a secondary observation. Bad science, but big pharma gets the win over the cheap generic (HCQ) that appears to be giving similar (if not greater) benefit outside the US.

 

I'll post some links tomorrow.

Edited by Dorian Grey, 01 May 2020 - 04:39 AM.

[Gal220]

I guess this Dr. Bruce Hollis will have more knowledge about Vitamin D since he has studied it for 40 years.

 

He says that he takes 6,000 iu a day to keep his immune system strong and he recommends the average

adult to take between 4,000 and 6,000 iu daily.

 

He says it takes about 3 months of supplementation to create a steady level.

 

https://www.wbtw.com...d-19-be-linked/
 

 

He doesnt appear to publish much, hard to say.  There does seem to be a consenus among several sources that 2000IU is good starting point - Weil, examine.com, linus pauling institute (thorough breakdown- https://lpi.oregonst...amins/vitamin-D) .

 

The real question is are they right to limit D  in terms of this specific virus?  Even then, most of them are recommending 1000IU.   Seems reasonable to me to recommend family members take 2000IU , if symptoms drop to 1000 IU.

[Florin]

Perhaps this explains some of the differences in outcome of men vs. women in covid infections:

 

Two potent antihistamines, clemastine and cloperastine, also displayed antiviral activity, as did the compound PB28 and the female hormone progesterone.

 

Yup, good catch. I noticed that too but forgot to mention it.

[joelcairo]

"We found and tested 47 old drugs that might treat the coronavirus: Results show promising leads and a whole new way to fight COVID-19"

 

https://theconversat...covid-19-136789

https://www.nature.c...1586-020-2286-9

 

 

Lesson 1 from this study: Do not take cough syrup containing dextromethorphan. The drug actually assists the virus in replicating.

 

Same as with potential treatments, it may be that at typical dosages there isn't a clinically measurable harmful effect. But it certainly won't be doing you any good.

[gamesguru]

Just saw an analysis of Fauci's remdesivir trial. They changed the parameters on the fly to get their desired result, enlarging the trial twice trying to reach statistical significance for mortality improvement. When that didn't work, they dropped mortality rate from a primary end point to a secondary observation. Bad science, but big pharma gets the win over the cheap generic (HCQ) that appears to be giving similar (if not greater) benefit outside the US.

 

I'll post some links tomorrow.

 

April 23rd there was a press release, "New data on Gilead’s remdesivir, released by accident, show no benefit for coronavirus patients. Company still sees reason for hope"

 

We should really be using these two drugs as way-points, not endgames.  Absorb what is useful, discard what is not, and add what is uniquely your own.  Currently we are discarding and adding nothing.

 

And in very sick people, a low side effect profile is essential.

 

We need alternative treatments for those with arrhythmias or diabetic retinopathy.

[gamesguru]

Possible involvement of nicotine, choline, histamine dysfunction with the cytokine storm.

 

Editorial: Nicotine and SARS-CoV-2: COVID-19 may be a disease of the nicotinic cholinergic system

7. Conclusions

 

In conclusion, we noticed that most of the clinical characteristics of severe COVID-19 could be explained by dysregulation of the cholinergic anti-inflammatory system. The observation that patients eventually develop cytokine storm which results in rapid clinical deterioration, led to the development of a hypothesis about the series of events associated with adverse outcomes in COVID-19 (Fig. 2). Once someone is infected with SARS-CoV-2, the immune system is mobilized. As the virus replicates, cell and viral debris or virions may interact with the nAChRs blocking the action of the cholinergic anti-inflammatory pathway. If the initial immune response is not enough to combat the viral invasion at an early stage, the extensive and prolonged replication of the virus will eventually block a large part the cholinergic anti-inflammatory pathway seriously compromising its ability to control and regulate the immune response. The uncontrolled action of pro-inflammatory cytokines will result in the development of cytokine storm, with acute lung injury leading to ARDS, coagulation disturbances and multiorgan failure. Based on this hypothesis, COVID-19 appears to eventually become a disease of the nicotinic cholinergic system.

 

Nicotine could maintain or restore the function of the cholinergic anti-inflammatory system and thus control the release and activity of pro-inflammatory cytokines. This could prevent or suppress the cytokine storm. This hypothesis needs to be examined in the laboratory and the clinical setting.

 

[Gal220]

Lesson 1 from this study: Do not take cough syrup containing dextromethorphan. The drug actually assists the virus in replicating.

 

Same as with potential treatments, it may be that at typical dosages there isn't a clinically measurable harmful effect. But it certainly won't be doing you any good.

 

Along those lines, anything else on the avoidance list?  Weil suggests stopping the following if symptoms - elderberry, isolated polysaccharide(mushroom extract), Echinacea , larch arabinogalactan, and vit D.

 

https://www.drweil.c...ut-coronavirus/

[lancebr]

Along those lines, anything else on the avoidance list?  Weil suggests stopping the following if symptoms - elderberry, isolated polysaccharide(mushroom extract), Echinacea , larch arabinogalactan, and vit D.

 

https://www.drweil.c...ut-coronavirus/

 

Well I might agree with most of those but why in the world would you stop Vitamin D when the studies now

clearly show that people with higher levels of Vitamin D have better outcomes.

 

That just sounds like bad advice.

[Gal220]

Well I might agree with most of those but why in the world would you stop Vitamin D when the studies now

clearly show that people with higher levels of Vitamin D have better outcomes.

 

That just sounds like bad advice.

 

I cant edit my post,  but I do plan on continuing to take 1000IU (2000IU if no symptoms) as mentioned above.  Luckily most 1 day multis have this now.

Edited by Gal220, 01 May 2020 - 03:51 PM.

[joelcairo]

Along those lines, anything else on the avoidance list?  Weil suggests stopping the following if symptoms - elderberry, isolated polysaccharide(mushroom extract), Echinacea , larch arabinogalactan, and vit D.

 

https://www.drweil.c...ut-coronavirus/

 

That's a speculative list, based on our imperfect understanding of how the virus causes a patient's systems to dysregulate. I didn't read his opinion on all of those, but in the case of mushroom extract I think his point was not to supplement anything that was potentially counterproductive. Personally I can't think of anything else to add offhand.

 

OTOH, dextromethorphan is shown to be an agonist (opposite of an antagonist) of a receptor that the virus uses to replicate itself. When tested in vitro, it caused the virus to replicate more successfully. As with every study I've ever read, the authors stress that more study is needed, but the results seem clear that if you don't urgently need dextromethorphan for a severe cough you should probably avoid it.

Edited by joelcairo, 01 May 2020 - 04:00 PM.

[gamesguru]

Bad news bears

 

LIVE: Trump Says FDA Has Approved Gilead Drug Remdesivir for Emergency Use

 

[Gal220]

Chris Masterjohn doesnt put much stock in the quercetin+zinc ionophore hypothesis

https://chrismasterj...ovid-19-updates

 

I guess we will find out shortly if he knows what he is talking about.

 

He does mention there are other ways for it to be beneficial, the DARPA study did not use zinc and still had excellent results in preventing the flu using 1000mg daily.

 

"I find the predicted inhibition of the 3CL protease by  realistic concentrations of quercetin to be promising, but I would like to see at a minimum a paper showing that quercetin has this effect in cells infected with the virus before I would consider adding it to my prevention regimen."

 

He doesnt mention it blocking ACE2 along with astragulas and Vitamin D as the Arizona Integrative University mentions in their youtube video - page 40 third post.

 

 

 

[Dorian Grey]

Bad news bears

 

LIVE: Trump Says FDA Has Approved Gilead Drug Remdesivir for Emergency Use

 

 

Aaand they're off!  It will be interesting to see how the remdesivir US model does compared to the HCQ model outside the US, particularly if the latter start using HCQ early/outpatient (and hopefully with zinc) like Costa Rica (CFR 0.86%).  Unfortunate that remdesivir is IV and probably will be used only for inpatient salvage (or will there be a pill?).  Personally, I'd like to start treatment before I'm circling the drain!  

 

If they've got it wrong, I foresee angry mobs with pitchforks & torches outside the FDA.  This could be the biggest blunder in medical history (or not!)

[sciack]

Interesting statistical work on Vitamin D deficiency and Covid-19 : https://www.sciencea...what-that-means

Edited by sciack, 01 May 2020 - 09:27 PM.

[Gal220]

That's a speculative list, based on our imperfect understanding of how the virus causes a patient's systems to dysregulate. I didn't read his opinion on all of those, but in the case of mushroom extract I think his point was not to supplement anything that was potentially counterproductive. Personally I can't think of anything else to add offhand.

 

OTOH, dextromethorphan is shown to be an agonist (opposite of an antagonist) of a receptor that the virus uses to replicate itself. When tested in vitro, it caused the virus to replicate more successfully. As with every study I've ever read, the authors stress that more study is needed, but the results seem clear that if you don't urgently need dextromethorphan for a severe cough you should probably avoid it.

 

Definite on the speculation of Weil's list, interesting his list and ChrIs Masterjohn's list of limits doesnt overlap except in limiting D.

 

He thinks you limit A, D, and calcium.  while avoiding Pelargonium Sidoides and Honeybee Propolis -   https://www.lesswron...onavirus-part-2

[Gal220]

Interesting statistical work on Vitamin D deficiency and Covid-19 : https://www.sciencea...what-that-means

 

Anyone found a news aggregator for covid .  Mercola has new article on exercise using blood flow restriction (good for older adults) but nothing about vitamin D on their page - https://fitness.merc...une-system.aspx

 

Chris goes over the new vit D info in detail and what he thinks it means - https://chrismasterj...d.com/covid-19/

 

Maybe this thread is the best source.

[Gal220]

Unfortunate that remdesivir is IV and probably will be used only for inpatient salvage (or will there be a pill?).  Personally, I'd like to start treatment before I'm circling the drain!  

 

As expected, Derek Lowe didnt think too much of remdesivir - https://blogs.sciencemag.org/pipeline/

 

Interesting thought about circling the drain. I would like to think all the integrative strategies would work before that point, but if not, would you opt for this drug, IV C, or something else? 

 

If I was a senior to prevent - sleep, exercise,  life extension multi(2000IU D, 25mg zinc, 200mcg selenium) + health booster(k2+E), quercetin/vitC(250mg 2x), digestive enzymes, Collagen, teaspoon cod oil(vitA+omegas).  Only thing I am really adding to a normal regimen is the quercetin.

[Dorian Grey]

As expected, Derek Lowe didnt think too much of remdesivir - https://blogs.sciencemag.org/pipeline/

 

Interesting thought about circling the drain. I would like to think all the integrative strategies would work before that point, but if not, would you opt for this drug, IV C, or something else? 

 

If I was a senior to prevent - sleep, exercise,  life extension multi(2000IU D, 25mg zinc, 200mcg selenium) + health booster(k2+E), quercetin/vitC(250mg 2x), digestive enzymes, Collagen, teaspoon cod oil(vitA+omegas).  Only thing I am really adding to a normal regimen is the quercetin.

 

I've actually given some thought to what I might do if I develop advanced COVID.  At 64 years of age with no kids, death doesn't frighten me nearly as much as living the last decade of my life with neurological damage, pulmonary fibrosis, or liver damage from remdesivir.  I'll be watching to see how this therapy pans out, but for now, I plan to stay at home if I get sick & perhaps have a "good death" in the worse case scenario.   

 

I worked in healthcare for 35 years, and have seen a lot of patients tormented with futile end of life treatment.  Nothing like watching your last sunrise at home, and not under the florescent lights in an ICU.  There's a reason for those doors with the 'No Admittance" sign.  Terrible things happen behind those doors.  On TV patients who "pull through" pull through bright eyed and bushy tailed.  In reality, a great many patients who survive their ICU adventure emerge broken beings in need of extended care.  Not my cup of tea!  I'll see you on the dark side of the moon.  

Edited by Dorian Grey, 02 May 2020 - 05:51 AM.

[lancebr]

Looks like this virus may be mutating:

 

https://www.biorxiv.....04.29.069054v1

Edited by lancebr, 02 May 2020 - 06:46 AM.

[albedo]

Looks like this virus may be mutating:

 

https://www.biorxiv.....04.29.069054v1

 

Overview: How Coronavirus Mutates and Spreads.
https://www.nytimes....-mutations.html

Punch line of the opinion: mutation seems slow. So I think tracking is possible. Strategy: TIT: Test, Isolate, Track

"...In fact, researchers have found that the coronavirus is mutating relatively slowly compared to some other RNA viruses, in part because virus proteins acting as proofreaders are able to fix some mistakes. Each month, a lineage of coronaviruses might acquire only two single-letter mutations. In the future, the coronavirus may pick up some mutations that help it evade our immune systems. But the slow mutation rate of the coronavirus means that these changes will emerge over the course of years..."

[Kalliste]

This vitamin D discussion is myopic. Vitamin D is a PROXY for Solar Exposure

 

What does that do? It helps blood flow more freely, it relaxes endothelial stuff via NO, it improves mitochondria function via Cytochrome C Oxidase, it stimulates synthesis of immune products in the skin.

 

You are not gonna get even 25% of this via any pills.

 

 

 

How does it work? The wavelengths from 600 to 900 nm pass through blood and water in tissue more easily than other wavelengths.  About 35% of the energy in this range is absorbed by a specific "proton pump" (cytochrome c oxidase, CCO, "complex IV") in mitochondria.  The light at 4 specific wavelengths "kick-start" the CCO pump into producing more cellular energy, ATP.  The CCO pump is very similar in all animals because the key proteins were inherited from light-assisted bacteria that were part of the first mitochondria.  The absorption spectrum of blood suddenly drops off to allow these wavelengths to pass through which indicates the evolution of hemoglobin may have been influenced by cells benefiting from these wavelengths.  The immediate increase in respiration that Sun causes by this mechanism may help animals increase their physical and mental activity during the day, in addition to the heat provided by the Sun that promotes the release of oxygen (myoglobin also absorbs these wavelengths) and basic warmth.  These wavelengths of the Sun can provide the optimum 4 J/cm^2 at a depth of 1 inch (using 1% transmission) after 1 to 3 hours of exposure in bright Sun, reaching all skin and a large percentage of muscle tissue in historically-thin humans with minimal clothing.

Evolution Theory Support: There are 5 indications that the benefit of red and near-infrared light is not an accident, but a highly "intelligent" and natural result of evolution. The indications are: 1) The proton pump is the last in a series of 3 pumps which places it in possibly the best location to pull the food conversion process along by "pushing" the final electrons through the chain. This creates a chemical "pull" (which is a real electrostatic "pull") on the electrons further back in the chain, which can prevent reactive oxygen leakage if not too much light is applied. 2) The pump absorbs primarily the red and near-infrared light and the remaining sunlight wavelengths are blocked by water and blood. 3) The pump is the primary absorber of these wavelengths in the body, very roughly 35%. 4) Oxygenated hemoglobin has a very sharp decline in it's ability to absorb red and near-infrared which indicates hemoglobin evolved specifically to allow these wavelengths to pass through. The CCO pump has a longer evolutionary history than hemoglobin because it was inherited from bacteria that formed the symbiotic relationship in mitochondria. (I first wrote this here in 2006 to evolutionarily "explain" why blood is red). Decendents of these bacteria still exist as purple bacteria which are used in research on the CCO pump. 5) Night-time levels of melatonin, but not day-time levels, have been shown by Tiina Karu to completely inhibit the positive effects of infrared light. This indicates that melatonin and its wide swings over 24 hours could have evolved to not inhibit the benefits of sunlight. Although large animals may have only 10% of their cells effectively exposed to light going into their bodies, small animals that existed when blood first evolved had 100% of their cells exposed so it should have been strong evolutionary pressure to get blood "right" in terms of how it lets light through.

https://heelspurs.com/led.html

 

 

I started taking C60 again

 

 

[Effect of fullerene C60-polyvinilpyrrolidone complexes on influenza virus reproduction].

 

Share this article Share with emailShare with twitterShare with linkedinShare with facebook

Abstract 

The capacity of water-soluble complexes of fullerene C60-polyvinylpyrrolidone to inhibit the replication of influenza viruses was studied. In contrast to remantadine, these complexes inhibit the replication of both A and B viruses (including the remantadine-resistant strains). The complexes inhibit influenza virus replication at all stages of replication cycle.

 

 

The H1N1 influenza A virus, which originated in swine, caused a global pandemic in 2009, and the highly pathogenic H5N1avian influenza virus has also caused epidemics in Southeast Asia in recent years. Thus, the threat from influenza A remains aserious global health issue, and novel drugs that target these viruses are highly desirable. Influenza A RNA polymeraseconsists of the PA, PB1, and PB2 subunits, and the N-terminal domain of the PA subunit demonstrates endonuclease activity.Fullerene (C60) is a unique carbon molecule that forms a sphere. To identify potential new anti-influenza compounds, wescreened 12 fullerene derivatives using anin vitroPA endonuclease inhibition assay. We identified 8 fullerene derivativesthat inhibited the endonuclease activity of the PA N-terminal domain or full-length PA proteinin vitro. We also performedinsilicodocking simulation analysis of the C60fullerene and PA endonuclease, which suggested that fullerenes can bind to theactive pocket of PA endonuclease. In a cell culture system, we found that several fullerene derivatives inhibit influenza Aviral infection and the expression of influenza A nucleoprotein and nonstructural protein 1. These results indicate thatfullerene derivatives are possible candidates for the development of novel anti-influenza drug

 

 

Carboxyfullerene (C60) is known as a photosensitizer for virus inactivation. Its regioisomer with C3 symmetry, named the C3 isomer, could also inactivate the dengue-2 virus without light when the dose of C3 isomer was increased to 40 microM, indicating the possible involvement of a light-independent mechanism. Further analysis showed that the C3 isomer blocked viral replication at the attachment and penetration stages, suggesting that a direct interaction between the C3 isomer and the virion is required for inactivation. The C3 isomer with a bipolar structure showed better lipid interaction and dengue-2 virus suppression than D3, another isomer that contains evenly distributed hydrophilic side chains. Moreover, the C3 isomer selectively inactivated enveloped viruses (viz., dengue-2 virus and Japanese encephalitis virus) instead of nonenveloped viruses (viz., enterovirus 71 and coxsackievirus B3). Collectively, these findings support the hypothesis that C3 isomer suppression of enveloped viruses is effected through its hydrophobic interaction with the viral lipid envelope. Our report, which demonstrates the light-dependent and -independent mechanisms of C60 on viral inactivation, will aid in the development of novel anti-viral agents for use against enveloped viruses.

 

 

We have developed and applied a computational strategy to increase the affinity of fullerene-based inhibitors of the HIV protease. The result is a ∼50-fold increase in affinity from previously tested fullerene compounds. The strategy is based on the design of derivatives which may potentially increase hydrophobic desolvation upon complex formation, followed by the docking of the hypothetical derivatives into the HIV protease active site and assessment of the model complexes so formed. The model complexes are generated by the program DOCK and then analyzed for desolvated hydrophobic surface. The amount of hydrophobic surface desolvated was compared with a previously tested compound, and if this amount was significantly greater, it was selected as a target. Using this approach, two targets were identified and synthesized, using two different synthetic approaches:  a diphenyl C₆₀ alcohol (5) based on a cyclopropyl derivative of Bingel (Chem. Ber. 1993, 126, 1957−1959) and a diisopropyl cyclohexyl C₆₀ alcohol (4a) as synthesized by Ganapathi et al. (J. Org. Chem.1995, 60, 2954−2955). Both showed tighter binding than the originally tested compound (diphenethylaminosuccinate methano-C₆₀, K_i = 5 μM) with K_i values of 103 and 150 nM, respectively. In addition to demonstrating the utility of this approach, it shows that simple modification of fullerenes can result in high-affinity ligands of the HIV protease, for which they are highly complementary in structure and chemical nature.

 

 

Synthesis of a fullerene derivative for the inhibition of HIV enzymes

https://pubs.acs.org...021/ja00068a006

 

 

Hemorrhagic shock/resuscitation involves overwhelming reactive oxygen species (ROS) that cause oxidative stress, inflammation, and subsequent tissue injury. We investigated the effects of the potent antioxidant carboxyfullerene (C3) on acute liver injury during hemorrhage shock/resuscitation. C3 infusion reduced the alanine aminotransferase (ALT) activity, methemoglobin content, malondialdehyde content, myeloperoxidase activity and expression levels of tumor necrosis factor -α and interleukin-6; it increased superoxide dismutase activity in the liver. The histologic injury score and apoptotic index were also markedly decreased after C3 treatment compared with the vehicle group. Additionally, C3-treated rats showed a significant decrease in nuclear factor-κB DNA binding capacity, which was preceded by reduced phosphorylation of the nuclear factor κB (NF-κB) p65 subunit in the liver. C3 nanoparticles ameliorate oxidative stress, the inflammatory response, and subsequent acute liver injury after hemorrhagic shock/resuscitation. These protective effects appear to be mediated through the inhibition of the nuclear factor-κB pathway. C3 treatment may be a promising strategy to improve tissue injury in hemorrhagic shock/resuscitation.

 

Did nothing in this trial

 

 

Anti-HIV properties of cationic fullerene derivatives

Abstrac

A series of regioisomeric bis-fulleropyrrolidines bearing two ammonium groups have been synthesized and their activities against HIV-1 and HIV-2 have been evaluated. Two trans isomers have been endowed with interesting antiviral properties, confirming the importance of the relative positions of the substituent on the C₆₀ cage. In addition, reduced amphiphilicity of molecules to other compounds previously reported decreases their cytotoxicity in CEM cell cultures. None of the compounds showed any inhibitory activity against a variety of DNA and RNA viruses other than HIV.

 

 

Inhibition of Group A Streptococcus Infection by Carboxyfullerene

ABSTRACT

The effect of a water-soluble trimalonic acid derivative of fullerene, carboxyfullerene, against Streptococcus pyogenes infection was tested. Pretreatment with carboxyfullerene was able to protect mice from S. pyogenes infection in an air pouch model. S. pyogenes-induced death and skin injury were inhibited dose dependently by carboxyfullerene. Administration of carboxyfullerene via the peritoneum and air pouch at 3 h post-S. pyogenes infection was able to protect 33% of mice from death. Surveys of exudates of the air pouch of carboxyfullerene-treated mice revealed that survival of infiltrating neutrophils was prolonged and that the bacteria were eliminated as a result of enhanced bactericidal activity of the neutrophils. Furthermore, carboxyfullerene was able to directly inhibit in vitro growth of S. pyogenes. These data suggest that carboxyfullerene can be considered an antimicrobial agent for group A streptococcus infection.

 

Does Carbon 60 (C60) Inhibit Viruses?

The C60 Show

https://poddtoppen.s...inhibit-viruses

 

 

[Mind]

Just saw an analysis of Fauci's remdesivir trial. They changed the parameters on the fly to get their desired result, enlarging the trial twice trying to reach statistical significance for mortality improvement. When that didn't work, they dropped mortality rate from a primary end point to a secondary observation. Bad science, but big pharma gets the win over the cheap generic (HCQ) that appears to be giving similar (if not greater) benefit outside the US.

 

I'll post some links tomorrow.

 

Agreed. Notice how quickly national media outlets touted a bad study to approve an expensive drug with significant side effects.

Edited by Mind, 02 May 2020 - 12:46 PM.