Antivirals Effective Against Coronavirus?

[Ecoclimber]

FYI

PrePrint:

"Scientists have found why new #coronavirus is so much more infectious - “Compared to (old) SARS’ way of entry, [the new] binding method is “100 to 1,000 times” as efficient”. Study is pre-print but it has been confirmed by another group.

When looking at the genome sequence of the new coronavirus... (scientists) found section of mutated genes that did not exist in SARS, but were similar to those found in HIV and Ebola.

This virus may use the packing mechanisms of other viruses such as HIV. According to the study, the mutation can generate a structure known as a cleavage site in the new coronavirus’ spike protein.

virus uses the outreaching spike protein to hook on to the host cell, but normally this protein is inactive. The cleavage site structure’s job is to trick human furin protein, so it will cut and activate spike protein and cause a “direct fusion” of viral+cellular membranes.

In a follow-up study, research team from Huazhong University of Science and Technology confirmed Ruan’s findings. The mutation could not be found in SARS, MERS or Bat-CoVRaTG13- considered the original source of the new coronavirus with 96 per cent similarity in genes.

This could be “the reason why #SARSCoV2 is more infectious than other coronaviruses”, Li wrote. Meanwhile, study by French scientist which was published in journal Antiviral Research on Feb 10, also found a “furin-like cleavage site” that is absent in similar coronaviruses.”

drugs targeting the furin enzyme could have potential to hinder virus’ replication. These include “a series of HIV-1 therapeutic drugs: Indinavir, Tenofovir Alafenamide, Tenofovir Disoproxil and Dolutegravir and hepatitis C drugs including Boceprevir and Telaprevir”.

Remdesivir seems the most efficacious drug to date.

VIA:
@EricDing

https://amp.scmp.com/news/china/society/article/3052495/coronavirus-far-more-likely-sars-bond-human-cells-scientists-say

Ian M. MacKay Phd
@MacKay
"Just a reminder (cough @abcnews
cough), COVID-19 isn't the virus.

COVID-19 are the signs and symptoms of disease *resulting from infection* by the virus, called SARS-CoV-2"

Eco

 

[junkcrap50]

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?

Yes, Cardarine (aka GW501516, GW0742, GW610742) is a PPAR-alpha agonist and also upregulates CPT2. It is mentioned in the articles I've linked. I've edited my "resveratrol" post to include Cardarine and its references.

I didn't mention it b/c I didn't recognize it's various names. Also, it's not available from a pharmacy or official" source.

EDIT: Also added Pioglitazone (Actos) to the post. As it upregulates CPT1 and fatty acid oxidation.

 

[ShepherdK]

However, resveratrol may be 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.

Resveratrol has terrible bioavailability - you would need to find a liposomal version for it to cross the gut.

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?

Cardarine was pulled from R&D because it is highly carcinogenic in almost all of the animal models they tested the drug against. Yep, it's a PPAR-Alpha agonist, so it should theoretically work like a *fibrate drug, but even most in the bodybuilding community steer clear of this one due to the risks.


Honestly the most important thing we need to do as a patient community is to ensure we are stocked up on all of the supplements/drugs/foods that keep us functioning. We don't know how COVID-19 will effect the ME/CFS community health-wise, but we can at least be prepared. We may fall into a higher risk group for the disease due to the immune system, energy regulation, and other issues we have daily (or just the opposite, who knows) - so being prepared for several weeks to months of quarantine might be a good idea.

Personally I'm stocking up on 3-6 months worth of my core supplements, prescription drugs, and whey protein. It's expensive, and hopefully unnecessary, but thankfully they will get used regardless if the disease becomes a pandemic.

 

[junkcrap50]

Honestly the most important thing we need to do as a patient community is to ensure we are stocked up on all of the supplements/drugs/foods that keep us functioning.

Yes. I agree. I posted this info, only for potential use in the emergency situation of cytokine storm and multi-organ failure. It was new research and may be particular to our subset. This would NOT be a prophylactic treatment and for emergency use only.

Note, I also edited and added Pioglitazone (Actos) as another potential upregulator of fatty acid oxidation, but no evidence of effect on CPT2.

 

[tdog333]

Resveratrol has terrible bioavailability - you would need to find a liposomal version for it to cross the gut.



Cardarine was pulled from R&D because it is highly carcinogenic in almost all of the animal models they tested the drug against. Yep, it's a PPAR-Alpha agonist, so it should theoretically work like a *fibrate drug, but even most in the bodybuilding community steer clear of this one due to the risks.

I haven't looked into it in awhile but I remember that they dosed the rats in the carcinogenic study with massive doses of cardarine, I also saw a study that showed cardarine prevented cancer, it's hard to know what to believe on this one, lots of conflicting data.

 

[junkcrap50]

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

Crap. You weren't kidding. Last time I bought it, it was like $40-50 for a bottle of capsules a couple years ago. They must be having some supply chain issues with china or something. When I bought it last time, I could only find it on amazon, not any supplement sites.

Looking into DADA (diisopropylamine dichloroacitate), I found two products that contain it: "Liverall" (a drug from Japan) and Synthergine (doesn't list amount of DADA). Both available online for much less.

Also, DADA was originally obtained from apricot nuclei and called pangamic acid or “vitamin B15”. So, you may get some trace amounts of DADA that way.

 

[Sushi]

Hand washing with soap and water is not very effective against pathogens compared to using 95 % ethanol hand sanitizers.

I had a quick look online for a pocket-sized hand sanitizer gel bottle containing around 95% ethanol, but could not find any. Most hand sanitizers are around 70% ethanol. 70% ethanol should be good enough to kill the Wuhan coronavirus; but if you want something that kills even non-enveloped viruses, then a gel containing around 95% ethanol would be better.

I just tried to order hand sanitizer on Amazon and most brands were out of stock. I found one that will deliver in about 10 days.

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

A doctor told me yesterday that it is acute respiratory distress syndrome that is responsible for most deaths. Having worked in Medical Intensive Care, I saw how very hard this syndrome is to manage once it sets in. I also saw an article saying: Oxygen therapy has been effective in the treatment of a critically ill patient infected with the new strain of coronavirus in South Korea, local health authorities said Friday.

 

[Hip]

Oxygen therapy has been effective in the treatment of a critically ill patient infected with the new strain of coronavirus in South Korea, local health authorities said Friday.

Yes, I've read supplemental oxygen is important for those suffering acute respiratory distress syndrome (ARDS) from the Wuhan coronavirus.

 

[Strawberry]

ensure we are stocked up on all of the supplements/drugs/foods that keep us functioning.

And we should wash those bottles when we receive them. You never know who put those bottles into the boxes.

 

[tdog333]

Crap. You weren't kidding. Last time I bought it, it was like $40-50 for a bottle of capsules a couple years ago. They must be having some supply chain issues with china or something. When I bought it last time, I could only find it on amazon, not any supplement sites.

Looking into DADA (diisopropylamine dichloroacitate), I found two products that contain it: "Liverall" (a drug from Japan) and Synthergine (doesn't list amount of DADA). Both available online for much less.

Also, DADA was originally obtained from apricot nuclei and called pangamic acid or “vitamin B15”. So, you may get some trace amounts of DADA that way.

Where did you see the liverall? I found some on https://bio-japan.net/ but that's the only place I've found it so far. Not sure how legitimate the website is.

 

[Rufous McKinney]

Yes, I've read supplemental oxygen is important for those suffering acute respiratory distress syndrome (ARDS) from the Wuhan coronavirus.

During my last episode of "normal" horrible stomach flu...and I'm in the ER: I really could hardly breathe from our Air Hungar symptom.

My lungs were uncongested. This symptom is extremely concerning to my version of ME.

So the respiratory aspects of this are really concerning.

 

[junkcrap50]

Oxygen therapy has been effective in the treatment of a critically ill patient infected with the new strain of coronavirus in South Korea, local health authorities said Friday.

Yes, I've read supplemental oxygen is important for those suffering acute respiratory distress syndrome (ARDS) from the Wuhan coronavirus.

Yes, and CPAP (with oxygenation I assume) has been studied to be helpful in SARS epidemic and used to treat many patients in 2003. However, I've read some confusing things on CPAP in ARDS, where it is said to be contraindicated. So, I'm unsure of CPAP's role. Perhaps it works only as an early intervention. See the info below and if you click to the reference's abstracts there's some good info on CPAP & SARS:

NIV, as either continuous positive airway pressure (CPAP) or bi-level pressure support, was commonly employed in many Chinese hospitals (Zhong & Zeng 2003; Luo & Qian 2003; Liu et al 2003; Xiao et al 2003; Zhao Z et al 2003; Wu et al 2003; Li H et al 2003) and in one hospital in Hong Kong (So et al 2003). Its use can improve oxygenation and tachypnea within an hour, and this may help to prevent adding further corticosteroids for respiratory failure (Liu et al 2003). In general, NIV was found to be able to avoid intubation and invasive ventilation in up to two-thirds of SARS patients with deterioration (Xiao et al 2003; Zhao Z et al 2003; Unpublished data from Hong Kong).

NIV can be given using a CPAP of 4-10 cm H2O or bi-level pressure support with an inspiratory positive airway pressure (IPAP) of <10 cm H2O and an expiratory positive airway pressure (EPAP) of 4-6 cm H2O. Contrary to the scenarios for non-SARS-related acute respiratory distress syndrome, higher pressures were generally not necessary and should be avoided whenever possible, because not only was there usually no additional clinical improvement observed, but it can also add to the risk of pneumothorax and pneumomediastinum. The latter conditions are known complications of SARS, even without assisted positive pressure ventilation (Peiris et al 2003b).

SOURCE: http://www.sarsreference.com/sarsref/treat.htm

 

[Sushi]

Yes, and CPAP (with oxygenation I assume) has been studied to be helpful in SARS epidemic and used to treat many patients in 2003. However, I've read some confusing things on CPAP in ARDS, where it is said to be contraindicated.

Doesn't CPAP just increased the pressure of normal air rather than adding oxygen? When I worked in Medical Intensive Care where there were many ARDS patients they always received supplemental oxygen.

 

[Wally]

https://www.dailymail.co.uk/health/...aim-antibiotics-market-treat-coronavirus.html

. . . A team of researchers at Norwegian University of Science and Technology had anti-virals as well as four antibiotics that treat staph and skin infections have been able to stop the virus in lab tests. . . .

‘Drug repurposing is a strategy for generating additional value from an existing drug by targeting diseases other than that for which it was originally intended,' said senior author Dr Denis Kainov, an associate professor at the Norwegian University of Science and Technology, in a press release.

'For example, teicoplanin, oritavancin, dalbavancin and monensin are approved antibiotics that have been shown to inhibit corona- and other viruses in the laboratory.'

However, major health organizations including the CDC and the WHO have, for years, attempted to inform and remind doctors and the public in no uncertain terms that antibiotics are not capable of killing viruses like the one that causes COVID-19. . . .

See, Research Proposal from the Norwegian University of Science and Technology https://www.researchgate.net/publication/338929057_Drug_candidates_for_treatment_of_China_2019-nCoV_coronavirus

For example, oritavancin, dalbavancin, monensin and emetine could be repurposed for treatment of 2019-nCoV infections (drugvirus.info). Oritavancin, dalbavancin and monensin are approved antibiotics, whereas emetine is an anti-protozoal drug. These 4 drugs have been shown to inhibit several corona- as well as other viral infections

https://www.mdpi.com/1999-4915/11/10/964/htm

To identify potential BSAAs, we have reviewed approved and investigational safe-in-man antiviral agents using drug bank and clinical trials websites, respectively. In addition, we reviewed investigational and approved safe-in-man antibacterial, antifungal, antiprotozoal, antiemetic, etc. agents, for which antiviral activities have been reported in PubMed.

 

[junkcrap50]

Doesn't CPAP just increased the pressure of normal air rather than adding oxygen? When I worked in Medical Intensive Care where there were many ARDS patients they always received supplemental oxygen.

Yes. You're right, but it may indirectly provide more oxygen because there is just more air being inhaled. However, providing pressure may still be beneficial in itself. In ARDS, the lungs fill up with fluid and the pressure helps keep the fluid out of the lungs so the cells can make use of more oxygen. At least that's my understanding.

 

[heapsreal]

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?

Not sure i understand. Does cardarine have antiviral effects? I think of it as more a metaboluc enhances ie increases exercise endurance, improves insulin sensitivity and decreases cholesterol etc. I havent read anything about infection or immune function, thatwould be cool.

 

[junkcrap50]

Not sure i understand. Does cardarine have antiviral effects? I think of it as more a metaboluc enhances ie increases exercise endurance, improves insulin sensitivity and decreases cholesterol etc. I havent read anything about infection or immune function, thatwould be cool.

You're correct. It is NOT antiviral (So I suppose the discussion is a bit off from the title). Cardarine stimulates ATP production from fat utilization.

It was part of a discussion on a paper on cytokine storm because it can help avoid an ATP crisis occurs. The paper showed that cytokines from a viral infection can strongly inhibit cellular metabolism. And I thought the paper would be relevant to ME/CFS patients, who might be at higher risk due to our ATP/energy issues.

EDIT: Typos

 

[heapsreal]

You're correct. It is NOT antiviral (So I suppose the discussion is a bit off from the title). Cardarine stimulates ATP production from fat utilization.

It was part of a discussion on a paper on cytokine storm because it can help avoid an ATP crisis occurs. The paper showed that cytokines from a viral infection can strongly inhibit cellular metabolism. And I thought the pit would be relevant to ME/CFS patients, who might be at higher risk due to our ATP/energy issues.

When i used it , i didnt notice anything obvious in general dayto day things. But when exercising i noticing a definite improvement in endurance. Just my thoughts but if one isnt at a level they can exercise at then im not sure you will see much from it. So maybe better suited to those cfsers currently in a milder state and want to exercise effectively???

 

[junkcrap50]

My doctor got this from Tailor Made Pharmacy (a peptide compounding pharmacy) regarding products they offer to combat the coronavirus. See attached image for complete details.

(Couldn't figure out how to upload or attach an email with links that work. Resave the txt file as ".html" and it should work.)

 

[Ecoclimber]

My Post #26 listed the medicine and oxygen supplementation used on Case WA1 at Providence Hospital as outlined in NEJM article. In China, doctors are trying other ART cocktails to slow replication.

Critical time now to take precautions for the home bound to stock up for several weeks as supply chain is being effected...25% container traffic down in LA ports. You can order groceries delivered to your home from your grocery store using their delivery service or use instantcart
@instantcart...not endorsing them just learned about from them from a patient.

This is a new virus so there is no immunity to #SARSC0V2, COVID2. The first case in WA was in Everett. It appears that lack of test kits and narrow parameters for testing, this virus was percolating for asymptomatic period for 6 weeks. Patient WA2 that was tested last week showed a similar strain as WA1.
1
Trevor Bedford @fredhutch

This Thread by @trvrb is interesting

I believe we're facing an already substantial outbreak in Washington State that was not detected until now due to narrow case definition requiring direct travel to China. 6/9

Additional Info:

Containment has failed (though it did buy us time) and we are facing a pandemic. However, if countries can enact effective non-pharmaceutical interventions, it appears that spread can be substantially mitigated.

Transmission is quite rapid without effective non-pharmaceutical interventions aka social distancing, with an epidemic estimated to double every 7 days

I think we likely have 5-10X underreporting in China (due to normal issues of reporting with disease with spectrum of severity), but not 100X. This suggests that a substantial fraction of infections are indeed severe

I've written before that #COVID19 has no evidence of genetic engineering and the "67bioweapon" theory has no grounds.

See, for example:
https://twitter.com/trvrb/status/1224207086013149184….
In this thread I wanted to directly address the theory of escape from lab in Wuhan. 1/21

This is the worst thing I’ve ever been right about. @statnews reported on Jan 26 based on my conversation with @HelenBranswell
my statement: “if it’s not contained shortly, I think we are looking at a pandemic”. https://statnews.com/2020/01/26/containing-new-coronavirus-may-not-be-feasible-experts-say/… 1/2

I know the infectious disease doctor at Evergreen Hospital in charge of #SARSCoV2 response team to the recent cases in King County. I will try to obtain additional info on treatment options

I will also make contact with fredhutch