Antivirals Effective Against Coronavirus?

[Hip]

https://www.ahpmedicals.com/pharmac...OIlxuThw3yImjfqm0C1LolVyK018yWRBoCQn0QAvD_BwE

This looks decent.

Careful with using povidone-iodine repeatedly on large areas of skin, as you can get quite a bit of iodine systemically absorbed into the body over time. I think it might be wise to dilute down this 10% solution of povidone-iodine to around a 1% solution, or even 0.2% solution, using water to dilute. More economical too.

I did a rough calculation showing that if you applied 1 ml of 0.2% solution of povidone-iodine to the skin, after some hours you will absorb about 100 mcg of iodine. That's acceptable, as high-dose iodine supplements are in the range of 15 mg = 15,000 mcg of iodine.

But if you used 1 ml of a 10% solution, then you would absorb about 5000 mcg on each application.



Note that you should not swallow povidone-iodine, as it is toxic, and may result in diarrhea. Whereas a regular tincture of iodine is non-toxic. But the reason povidone-iodine and not a regular tincture of iodine is used for disinfection purposes is because the former releases its iodine slowly over many hours, and this is why is continues to disinfect the skin it is applied to for several hours.

 

[Rufous McKinney]

Below is the introductory paragraph from THIS ARTICLE: When I first started hearing about the Coronavirus, my first thought was that it could likely be relatively easily treated with IV Vitamin C, which has been demonstrated to cure polio, H1N1, and much more...

Thought I would mention that Vitamin C is considered very "cold"....and in chinese medicine, can be contraindicated...particularly if one has Spleen Qi deficiencies.

I experience these deficiencies and therefore, taking alot of Vitamin C is contra-indicated in my body based upon its existing inbalances.

Here is some opinion on affects of diet and Vit C on the body:

http://www.iritaichi.org/The_Chinese_Diet.pdf

I am currently finding that I experience considerable trouble when I don't follow the basic diet. I even convince myself - Oh this will be great...and instead its so very NOT GREAT.

 

[pamojja]

25g in 50ml @pamojja

Hope they will adjust. In such a high concentration ascorbate IVs can really be painful. That's why usually a 500 ml solultion is recommented for a up to 50g ascorbate IV, and 1000ml for a up to 100g IV. And even higher doses are given in single IVs, if the blood ascorbate levels don't rise sufficiently in individuals.

But even the 25g per day (somewhere else I read daily for 7 days) could show some beneficial effects, if all the study-participants don't withdraw because of the pain.

 

[heapsreal]

Arbidol would be worth looking into. It works in many ways.
BiochemistryEdit
Umifenovir inhibits membrane fusion.[3] Umifenovir prevents contact between the virus and target host cells. Fusion between the viral capsid and the cell membrane of the target cell is inhibited. This prevents viral entry to the target cell, and therefore protects it from infection.[9]
Some evidence suggests that the drug's actions are more effective at preventing infections from RNA viruses than infections from DNA viruses.[10]
As well as specific antiviral action against both influenza A and influenza B viruses, umifenovir exhibits modulatory effects on the immune system. The drug stimulates a humoral immune response, induces interferon-production, and stimulates the phagocytic function of macrophages.[11]

Then id say drugs like immunovir/isoprinosine and cycloferon which increase interferon and nk function.

 

[godlovesatrier]

Hope they will adjust. In such a high concentration ascorbate IVs can really be painful. That's why usually a 500 ml solultion is recommented for a up to 50g ascorbate IV, and 1000ml for a up to 100g IV. And even higher doses are given in single IVs, if the blood ascorbate levels don't rise sufficiently in individuals.

But even the 25g per day (somewhere else I read daily for 7 days) could show some beneficial effects, if all the study-participants don't withdraw because of the pain.

They did say the pump only allows a certain amount into the patient per hour/minute so it might still be ok. But I have no idea about vitamin c dosing for immune regulation when ill with a virus.

 

[Rufous McKinney]

The latest from Nature- looking at how the Chinese and others are evaluating various treatments for coronavirus.

https://www.nature.com/articles/d41586-020-00444-3

Several antivirals are discussed. One chinese herb....

 

[godlovesatrier]

Bad how we do so much research when we do terrible things to each other or the world produces some sort of ill that causes us to take so much action.

Saying that the article is right. Carried out under the wrong conditions the work will mean nothing.

 

[Rufous McKinney]

report on potential progress on a vaccine for Corona virus...

https://www.statesman.com/news/2020...ical-breakthroughrsquo-in-coronavirus-vaccine

 

[junkcrap50]

It seems the cause of death in COVID is either cytokine storm or acute respiratory distress syndrome.

This research may be very important in CFS as one pathway for cytokine storm is an ATP crisis. The therapy of DCA, bezafibrate, & L-carnitine can help prevent the ATP crisis.

https://www.ncbi.nlm.nih.gov/pubmed/27566378
Energy metabolic disorder is a major risk factor in severe influenza virus infection: Proposals for new therapeutic options based on animal model experiments.
Kido H1, Indalao IL2, Kim H3, Kimoto T4, Sakai S5, Takahashi E6.
Author information
Abstract
Severe influenza is characterized by cytokine storm and multiorgan failure. Influenza patients with underlying diseases show a rapid progression in disease severity. The major mechanism that underlies multiorgan failure during the progressive stage of infection, particularly in patients with underlying risk factors, is mitochondrial energy crisis. The relationship between the factors that determine infection severity, such as influenza virus, cytokines, cellular trypsin as a hemagglutinin processing protease for viral multiplication, accumulation of metabolic intermediates and ATP crisis in mitochondria, is termed the "influenza virus-cytokine-trypsin" cycle. This occurs during the initial stages of infection, and is interconnected with the "metabolic disorders-cytokine" cycle in the middle to late phase of infection. Experiments using animal models have highlighted the complex relationship between these two cycles. New treatment options have been proposed that target the ATP crisis and multiorgan failure during the late phase of infection, rather than antiviral treatments with neuraminidase inhibitors that work during the initial phase. These options are (i) restoration of glucose oxidation in mitochondria by diisopropylamine dichloroacetate, which inhibits infection-induced pyruvate dehydrogenase kinase 4 activity, and (ii) restoration of long-chain fatty acid oxidation in mitochondria by l-carnitine and bezafibrate, an agonist of peroxisome proliferation-activated receptors-β/δ, which transcriptionally upregulates carnitine palmitoyltransferase II. The latter is particularly effective in patients with influenza-associated encephalopathy who have thermolabile and short half-life compound variants of carnitine palmitoyltransferase II.

https://www.ncbi.nlm.nih.gov/pubmed/24865588
Diisopropylamine Dichloroacetate, a Novel Pyruvate Dehydrogenase Kinase 4 Inhibitor, as a Potential Therapeutic Agent for Metabolic Disorders and Multiorgan Failure in Severe Influenza
Kazuhiko Yamane, 1 Irene L. Indalao, 1 Junji Chida, 1 Yoshikazu Yamamoto, 2 Masaaki Hanawa, 2 and Hiroshi Kido 1 , *
Abstract
Severe influenza is characterized by cytokine storm and multiorgan failure with metabolic energy disorders and vascular hyperpermeability. In the regulation of energy homeostasis, the pyruvate dehydrogenase (PDH) complex plays an important role by catalyzing oxidative decarboxylation of pyruvate, linking glycolysis to the tricarboxylic acid cycle and fatty acid synthesis, and thus its activity is linked to energy homeostasis. The present study tested the effects of diisopropylamine dichloroacetate (DADA), a new PDH kinase 4 (PDK4) inhibitor, in mice with severe influenza. Infection of mice with influenza A PR/8/34(H1N1) virus resulted in marked down-regulation of PDH activity and ATP level, with selective up-regulation of PDK4 in the skeletal muscles, heart, liver and lungs. Oral administration of DADA at 12-h intervals for 14 days starting immediately after infection significantly restored PDH activity and ATP level in various organs, and ameliorated disorders of glucose and lipid metabolism in the blood, together with marked improvement of survival and suppression of cytokine storm, trypsin up-regulation and viral replication. These results indicate that through PDK4 inhibition, DADA effectively suppresses the host metabolic disorder-cytokine cycle, which is closely linked to the influenza virus-cytokine-trypsin cycle, resulting in prevention of multiorgan failure in severe influenza.

 

[junkcrap50]

Arbidol would be worth looking into. It works in many ways.

Then id say drugs like immunovir/isoprinosine and cycloferon which increase interferon and nk function.

I've been searching on PR about arbidol, cycloferon, and other interferon inducers. I found that cycloferon helped you significantly. Is that correct? Did you take oral or injectable cycloferon?

I'm looking at both for 2019-nCoV / COVID-19. But it's hard to tell if aribidol or cycloferon really work or not. There's some studies, but it only being used in Russia & China isn't that helpful. Looks like arbidol was studied in SARS back in 2003.

Do you have more info on those drugs? How do they compare to each other in terms of raising interferon? I guess arbidol would be better if I had to choose one, because it also inhibits viral-cell fusion.

 

[heapsreal]

I've been searching on PR about arbidol, cycloferon, and other interferon inducers. I found that cycloferon helped you significantly. Is that correct? Did you take oral or injectable cycloferon?

I'm looking at both for 2019-nCoV / COVID-19. But it's hard to tell if aribidol or cycloferon really work or not. There's some studies, but it only being used in Russia & China isn't that helpful. Looks like arbidol was studied in SARS back in 2003.

Do you have more info on those drugs? How do they compare to each other in terms of raising interferon? I guess arbidol would be better if I had to choose one, because it also inhibits viral-cell fusion.

Ive used both injectable and oral cycloferon. Injectable seemed better. I have had some before and after nk function testing on injectable cycloferon and it did increase my nk function. Increasing interferon is known to increase nk function.

My experience with possible ebv/cmv reactivation was that cycloferon was much better than arbidol but it could be different for flu type viruses etc.

Not much research written in english on these substances unfortunately.

 

[stefanosstef]

I consider Zinc (citrate or picolinate), C and garlic extract with high allicin content (no kyolic or black garlic)
ncbi.nlm.nih.gov/pubmed/11697022
a solid strategy to strengthen the immune system.That's what I'm taking at the moment, because I'm certain it will spread soon at least in my country (Europe).

 

[Rufous McKinney]

The therapy of DCA, bezafibrate, & L-carnitine can help prevent the ATP crisis.

this seems like a very SIGnificant recommendation....Must get our hands on these things.

Will doctors give us an RX for bezafibrate?

 

[Ecoclimber]

Preparations need to be taken now! This is disease at current levels is above the Spanish flu pandemic and may go on for 18 months .#COVID19 New data from China buttress fears about high coronavirus fatality rate, WHO expert says.Transmission is quite rapid without effective non-pharmaceutical interventions aka social distancing, with an epidemic estimated to double every 7 days
https://mobile.twitter.com/trvrb
I think we likely have 5-10X underreporting in China @trvrb

Need to prepare for total disruption in life, quarantine. 40-60% will get this disease. 20% severe meaning 3-4 weeks in hospital on ventilator/respirator. RO in some places 3.3 -4.4 CFR ~2 Hospitals may be over run. Critical care could be maxed out. There will be difficulty in supply chain supplying shortages. Many busineses could be closed

Stock up on Food, medical supplies, N 95 masks, gogles cleaning supplies clorax, bleach, hydrogen proxide, ethnol 3 mos supply of medicine need to be gathered now for 2-3 month disruption in services, medical, transportation, lack of facilities. Covid19 can last on surfaces for 9 days

Researchers From Sweden, Germany and China Say WHO Has Underestimated Transmissibility Of Coronavirus. It is airborne H2H

it is a stealth virus able to be asymptomaic for 24-27 days while spreading infection before symptoms show.

College London has estimated that about two-thirds of the cases exported from China have yet to be detected

Despite Fake Figures. 14 Percent Of “Cured” Coronavirus Patients In Guangdong, China Tested Positive Again

There is too many unanswered questions on China figures. This virus # SARCoV2 is still unpredictable. There is indication of virus mutating making it more viral to younger age group

Be Prepared
Eco

 

[stefanosstef]

40-70% will be infected worldwide (Harvard epidemiology professor), more than 53 million deaths (AI prediction)

 

[Rufous McKinney]

The therapy of DCA, bezafibrate, & L-carnitine can help prevent the ATP crisis.

I just ordered DCA....but is that the correct form???....did i make a mistake not ordering DADA? (I went looking for DCA, not DADA...)

Has anyone tried to get this bezafibrate? Will doctors write an RX? What might it cost?

 

[junkcrap50]

I just ordered DCA....but is that the correct form???....did i make a mistake not ordering DADA? (I went looking for DCA, not DADA...)

No, DADA and DCA are essentially the same. The difference is that DADA does not have the peripheral neuropathy side effects that DCA can have. They both agonize PDH enzyme and work via the same mechanism. I couldn't find DADA easily, but is supposedly a readily available supplement in Japan (where the study was done).

 

[junkcrap50]

Has anyone tried to get this bezafibrate? Will doctors write an RX? What might it cost?

I have not looked into buying bezafibrate very much yet. I just assumed the local pharmacy because I thought it was just an old lipid lowering drug.

However, bezafibrate, I just recently realized/learned, is NOT available in the US. I looked into other lipid lowering fibrates available in the US, like gemfibrozil, and found they would NOT work as valid subsitutions, because of other fibrates agonistic specificity on receptor types.

Looking at the paper I linked above, as well as this one by the same author (Bezafibrate upregulates carnitine palmitoyltransferase II expression and promotes mitochondrial energy crisis dissipation in fibroblasts of patients wwith influenza-associated encephalopathy), bezafibrate's importance is to upregulate CPT2 enzyme (enzyme that uses fatty acids in the mitochondria), via PPAR agonism.

Other fibrates are all also PPAR agonists. But bezafibrate is unique in that it is a pan-PPAR agonist, which upregulates all PPAR receptor types (alpha, detla, gamma). PPAR-delta is the only receptor type that upregulates CPT2. Other fibrates are selective and mostly work on PPAR-alpha, thus not providing the CPT2 boosting effect.

References:
This paper showed only PPAR-delta agonists increased CPT, specifically including bezafibrate:

Accordingly, we show that a 48-h treatment of CPT2-deficient myoblasts by bezafibrate restored FAO in patient cells. Specific agonists of PPARdelta (GWdelta 0742), and, to a lower extent, PPARalpha (GWalpha 7647) also stimulated FAO in control myoblasts. However, when tested in CPT2-deficient myoblasts, only the delta-agonist was able to restore FAO, whereas the alpha-agonist had no effect.
...Bezafibrate and GWdelta 0742 increased residual CPT2 activity and normalized long-chain acylcarnitine production by deficient cells.
...Furthermore, these data also illustrate a selective control of beta-oxidation enzyme gene expression by PPARdelta, with no contribution of PPARalpha.

Source: Peroxisome proliferator activated receptor delta (PPARdelta) agonist but not PPARalpha corrects carnitine palmitoyl transferase 2 deficiency in human muscle cells.

This paper looked at genetic CPT2 deficiency and found only bezafibrate works:

To address this question, fibroblasts from patients with mild or severe CPT2-deficiency (Table 1) were treated in parallel with each of the four different molecules of the fibrate group: [bezafibrate] (BZ), fenofibrate, ciprofibrate, and gemfibrozil, commonly used for the treatment of hyperlipidemia. Typically, none of the fibroblasts derived from severely affected patients responded to fibrates. Furthermore, BZ was the only fibrate capable to upregulate FAO in fibroblasts from mildly affected patients, via an activation of CPT2 gene expression [78], later confirmed by other authors [79].
...
In parallel, exposure of myoblasts to high-affinity PPAR ligands revealed that correction of CPT2 deficiency was only achieved after treatment with a PPAR delta agonist, while a PPAR alpha agonist had no effect. Thus, CPT2 gene expression is under specific control of PPAR delta isoform in human muscle cells, and this explained why, among the four tested fibrates, BZ was the only efficient one. Indeed, BZ is known to bind the alpha and delta PPAR isoforms, whereas the other fibrates are strict PPAR alpha agonists [81,82,83].

Source: Mitochondrial Genetic Disorders: Cell Signaling and Pharmacological Therapies

 

[junkcrap50]

However, resveratrol may be/is a valid substitute for bezafibrate.

This study also found that resveratrol increased CPT2 activation to similar levels as bezafibrate as well as working synergistically with bezafibrate. So resveratrol may work as a substitute.

Fibroblasts treated, with 75 µM RSV for 48 h exhibited markedly enhanced FAO rates in cell lines with mild FAO deficiency, i.e., the myopathic form of CPT2 or VLCAD deficiency, leading to restore normal flux, while no effect was found in fibroblasts from patients with the severe form of the deficiencies [100]. Interestingly, we found that the magnitude of FAO increases triggered by this natural compound (RSV) were as large as those induced by [bezafibrate] (BZ).

Source: Mitochondrial Genetic Disorders: Cell Signaling and Pharmacological Therapies

Cardarine (GW50516 aka GW0742) would also be a valid subsititute.

The same papers I quoted mentions GW0742, which is a stronger version of GW50516, as working as well. I didn't mention/highlight it because it's not an I didn't recognize GW0742 as GW50516.

GWdelta 0742 increased CPT2 mRNA levels, whereas no change in CPT2 transcripts was found in response to GWalpha 7647. Bezafibrate and GWdelta 0742 increased residual CPT2 activity and normalized long-chain acylcarnitine production by deficient cells.

SOURCE: Peroxisome proliferator activated receptor delta (PPARdelta) agonist but not PPARalpha corrects carnitine palmitoyl transferase 2 deficiency in human muscle cells.

The effects of BZ on CI and CIV activity could be mimicked by treatment of control and patient cells with the PPAR delta agonist GW0742, while the PPAR alpha agonist had no effect.

Source: Mitochondrial Genetic Disorders: Cell Signaling and Pharmacological Therapies

In this model, bezafibrate and GW501516 increased the levels of hepatic mRNAs associated with fatty acid beta-oxidation [acyl-CoA oxidase (ACO), carnitine palmitoyltransferase-1 (CPT-1), liver-fatty acid binding protein (L-FABP) and peroxisomal ketothiolase], and reduced the levels of those associated with inflammatory cytokines or chemokine [transforming growth factor (TGF)-beta1, interleukin (IL)-6, IL-1beta, monocyte chemoattractant protein (MCP)-1, tumor necrosis factor (TNF) alpha and nuclear factor (NF)-kappaB1].

SOURCE: Effects of bezafibrate, PPAR pan-agonist, and GW501516, PPARdelta agonist, on development of steatohepatitis in mice fed a methionine- and choline-deficient diet.

Pioglitazone (Actos) a common diabetes/metabolic syndrome drug is a PPAR-gamma agonist, which has some fatty acid oxidation upregulation. But I can't find any direct evidence it upregulates CPT2, onliy CPT1.

Pioglitazone treatment significantlyincreased mitochondrial copy number and expression offactors involved in mitochondrial biogenesis, includingperoxisome proliferator–activated receptor (PPAR)-co-activator-1and mitochondrial transcription factor A.Treatment with pioglitazone stimulated the expression ofgenes in the fatty acid oxidation pathway, including car-nitine palmitoyltransferase-1, malonyl-CoA decarboxyl-ase, and medium-chain acyl-CoA dehydrogenase. Theexpression of PPAR-, a transcriptional regulator of genesencoding mitochondrial enzymes involved in fatty acidoxidation, was higher after pioglitazone treatment.

SOURCE: Pioglitazone Induces Mitochondrial Biogenesis inHuman Subcutaneous Adipose Tissue In Vivo

 

[tdog333]

However, bezafibrate, I just recently realized/learned, is NOT available in the US. I looked into other lipid lowering fibrates available in the US, like gemfibrozil, and found they would NOT work as valid subsitutions, because of other fibrates agonistic specificity on receptor types.

How about GW501516 aka "Cardarine"? It's used by athletes as a "research chemical" in order to improve endurance and lipids. I read about it a few years ago but it just came to my mind as I believe I remember it to be a strong PPAR delta agonist?

Can someone look into this further?

Also, where are you getting DCA/DADA from? On amazon it's like $200, and any preference on the type of carnatine?