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Experimental Coronavirus Treatments to Watch - Secular Sanity - Apr 1, 2020

Here’s a list of some of the contenders.

COVID-19 Treatment and Vaccine Tracker

They all look pretty promising but there was an older study on an antiviral medication that was using modified sugars that I thought looked hopeful. I could have missed it but I didn’t see on the list.

Here’s the paper that I was interested in.


New Treatment Made From Sugar Could Help Fight Viral Outbreaks

"An international team of researchers has created a new antiviral material, essentially made from sugar, that is able to “destroy viruses on contact and may help in the fight against viral outbreaks.”

The scientists, from The University of Manchester, the University of Geneva (UNIGE) and the EPFL in Lausanne, Switzerland, say that the treatment shows promise in treating herpes simplex, respiratory syncytial virus, hepatitis C, HIV, and Zika virus - to name a few.

Current antiviral drugs work by inhibiting virus growth, but they are not always reliable as viruses can mutate and become resistant to these treatments.

This time around, the team showed that the outer shell of a virus can be disrupted using modified sugar molecules, thereby destroying the infectious particles on contact, as oppose to simply restricting its growth.

In work published in Science Advances, the team showed that they successfully engineered new modified molecules using natural glucose derivatives, known as cyclodextrins. The molecules attract viruses before breaking them down on contact, destroying the virus and fighting the infection.

The team has “successfully engineered a new molecule, which is a modified sugar that shows broad-spectrum antiviral properties,” explained Dr Samuel Jones, from The University of Manchester. “The antiviral mechanism is virucidal meaning that viruses struggle to develop resistance. As this is a new type of antiviral and one of the first to ever show broad-spectrum efficacy, it has potential to be a game changer in treating viral infections.”

The University of Manchester says that the molecule is patented and a spin-out company is being set up to continue pushing this new antiviral towards real-world use."

Here’s the original paper.

Modified cyclodextrins as broad-spectrum antivirals



https://www.youtube-nocookie.com/embed/dKNbRRRFhqY

Furin Cleavage Site

"It is important to note that other beta coronaviruses do not contain this cleavage site. SARS-CoV, which is closely related to the newest SARS-CoV-2 strain, does not bear a cleavage site."

How Furin and ACE2 Interact with the Spike Protein on SARS-CoV-2

The spike protein attaches to our cells and allows the virus to enter and inject its RNA. The insertion of its RNA building blocks adds four amino acids and creates a site in the protein for an enzyme (furin). Furin is made in our cells. The furin cleavage site had been particularly interesting to the researches. It's this ability that the virus acquired that makes it more contagious. 

The insertion also creates places where sugar molecules can attach to the spike protein, which creates a protective shield that protects the virus from our immune system. I guess you could call it "sugar coating". The sugars (glycoproteins) on the spike acts as camouflage. Knowing what to attack requires immune cells to distinguish self from foreign, and sugars play a key role, not only in pathogens, but cancer cells, as well.

RE: Experimental Coronavirus Treatments to Watch - C C - Apr 2, 2020

(Apr 1, 2020 05:20 PM)Secular Sanity Wrote: [...] Here’s the paper that I was interested in.
[spoiler]

New Treatment Made From Sugar Could Help Fight Viral Outbreaks [...]


Hmm... Cyclodextrins hailed as non-toxic and yet there's (probably trivial to humans) hearing loss in tested cats and kidney effects in mice that have been hindering progress for some uses. 

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0053280

https://www.nature.com/articles/s41598-019-53890-z

RE: Experimental Coronavirus Treatments to Watch - Secular Sanity - Apr 2, 2020

(Apr 2, 2020 10:34 PM)C C Wrote:
(Apr 1, 2020 05:20 PM)Secular Sanity Wrote: [...] Here’s the paper that I was interested in.
[spoiler]

New Treatment Made From Sugar Could Help Fight Viral Outbreaks [...]


Hmm... Cyclodextrins hailed as non-toxic and yet there's (probably trivial to humans) hearing loss in tested cats and kidney effects in mice that have been hindering progress for some uses. 

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0053280

https://www.nature.com/articles/s41598-019-53890-z

Yeah, I saw that and it made me wonder if that might be the cause of hearing loss with opiate abuse.

RE: Experimental Coronavirus Treatments to Watch - Secular Sanity - Apr 9, 2020

So, anyone who’s reading this should understand by now that COVID-19 utilizes the Angiotensin-converting enzyme-2 as a cellular entry receptor.

I think that this is one of the reasons that they advised us to discontinue the use of Ibuprofen because it increases ACE-2 receptors. The assumption was that a higher ACE2 expression might lead to a higher risk of infectivity. Since higher levels of ACE-2 were found both in COPD patients and current smokers they thought that a higher expression might also lead to a more severe infection, which they thought might explain why the mortality rate for virus is higher for men than women in China where two thirds of Chinese men smoked.
The concern began after a study in THE LANCET, which stated that ibuprofen boosts the angiotensin-converting enzyme 2 (ACE2), which may facilitate and worsen COVID-19. As a result, WHO originally warned most patients to stick with acetaminophen, which is also known as paracetamol or Tylenol. [source]
However, ACE-2 is an immunomodulator and several reports indicate that ACE-2 expression is dramatically reduced with aging. This is one of the explanations as to why infants and younger children, who are normally at a higher risk, aren't experiencing a more severe form.
A recent study showed that ACE2 is also highly expressed in the mouth and tongue, granting the virus easy access to a new host. ACE2 receptor abundance goes down in the elderly in all these tissues, but, counterintuitively, this might place them at a greater risk of severe illness.

This is because the ACE2 enzyme is an important regulator of the immune response, especially inflammation. It protects mice against acute lung injury triggered by sepsis. And a 2014 study found that the ACE2 enzyme offers protection against lethal avian influenza. Some patients with better outcomes had higher levels of the protein in their sera, and turning off the gene for ACE2 led to severe lung damage in mice infected with H5N1, while treating mice with human ACE2 dampened lung injury.

A fall in ACE2 activity in the elderly is partly to blame for humans’ poorer ability to put the brakes on our inflammatory response as we age, according to emailed comments from Hongpeng Jia of Johns Hopkins Medicine. Reduced abundance of ACE2 receptors in older adults could leave them less able to cope with SARS-CoV-2, says Baric, though the hypothesis still needs more research. [source]
In summary, through integrating public genomics, epigenomics and transcriptomics data, we examined whether variation of the SARS-CoV2 receptor ACE2 gene expression in different tissues across individuals can explain the differences in infection susceptibility and outcome. Our findings are contrary to the expectation from ACE2 being only a receptor for the virus, instead, its expression level is high in Asian females and young people, those who are known to be less susceptible, and even less inflicted by severe or fatal outcome, while it is low in males, further decrease with age and T2D, those who are most susceptible to bad outcome, suggesting at a population level a negative correlation between ACE2 expression and CovID19 severity and fatality. [source]
Angiotensin converting enzyme-2 has been linked to other lung diseases such as idiopathic pulmonary fibrosis. Low levels of ACE-2 have been shown to increase the likelihood of permanent damage to the lungs with the development of scar tissue. The data indicate that ACE-2 protects against lung fibrogenesis by limiting local accumulation of ANG II. They also suggest that downregulation of ACE-2 may be a critical profibrotic event in IPF. 

Normally, ACE-2 dampens the immune system response. So, now if we think about it for a second, when the COVID-19 virus binds with the ACE-2 receptors, the virus and the ACE-2 receptor is internalized within the cell. IOW, both the virus and the ACE-2 receptor enters the cell, which means that the ACE-2 receptors are decreased. Therefore, the protective dampening role that ACE-2 receptors play in our inflammatory response may lead to a more severe reaction.

There are some reports of this virus causing cytokine storms similar to the 1918 pandemic, which are normally cause by a superantigens, but we don’t know if this virus is a superantigen or not. It may have a different mechanism.

Additional sources:

"Cardiologists say several scenarios could be unfolding: The heart may struggle to pump blood in the absence of enough oxygen; the virus may directly invade heart cells; or the body, in its attempt to eradicate the virus, may mobilize a storm of immune cells that attack the heart." 

The mysterious connection between the coronavirus and the heart

Heart Damage in COVID-19 Patients Puzzles Doctors

Brain Images Reveal Possible COVID-19-Related "Cytokine Storm"

In the eye of the COVID-19 cytokine storm

RE: Experimental Coronavirus Treatments to Watch - Zinjanthropos - Apr 9, 2020

Just read an article about Covid-19 and blood thinners. Don't know what to make of it. I've had atrial fibrillation going on 20 years. I'm on anti-coagulant blood thinner (dabigitran) for life. Article said that I'm probably not as high a risk as someone taking a blood thinner who has actual heart disease, had a stroke or lung issues but I'm still a bit of a risk should I catch it. Have blood pressure issue but I take pills for that too. 

Why do anti-coagulants and their ilk pose a problem? Do they become less effective because of the virus?

RE: Experimental Coronavirus Treatments to Watch - Secular Sanity - Apr 10, 2020

(Apr 9, 2020 08:41 PM)Zinjanthropos Wrote: Just read an article about Covid-19 and blood thinners. Don't know what to make of it. I've had atrial fibrillation going on 20 years. I'm on anti-coagulant blood thinner (dabigitran) for life. Article said that I'm probably not as high a risk as someone taking a blood thinner who has actual heart disease, had a stroke or lung issues but I'm still a bit of a risk should I catch it. Have blood pressure issue but I take pills for that too. 

Why do anti-coagulants and their ilk pose a problem? Do they become less effective because of the virus?

I’m not sure but I don’t think that simply being on anticoagulants increases your risk. If anything, it’s probably the underlying condition. From what I’ve read, they seem to be arguing for the use of them and even increasing the dosage because they’re seeing more clotting in severe cases.

Anticoagulant Treatment is Associated with Decreased Mortality in Severe Covid-19 Patients

"As U.S. cases have skyrocketed, it has also become clear that hospitalized patients often develop blood clots despite being on prophylactic anticoagulation, he told MedPage Today.

"The question is whether everybody with COVID-19 in the hospital should be on blood thinners, and the answer is probably yes," he said. "Should they be on higher than usual prophylactic doses? And the answer is possibly yes."

Anticoagulation Guidance Emerging for Severe COVID-19

RE: Experimental Coronavirus Treatments to Watch - Zinjanthropos - Apr 10, 2020

Quote:"The question is whether everybody with COVID-19 in the hospital should be on blood thinners, and the answer is probably yes," he said. "Should they be on higher than usual prophylactic doses? And the answer is possibly yes."


Thanks SS. Makes me feel a little better. I take 150mg dose twice a day. I have a head start should I catch it. Regardless so much stuff on the internet that you still have to proceed with caution.

Does it mean that Covid patients are also dying of stroke or cardio related problems and not just pneumonia? Do we know those percentages if so?

RE: Experimental Coronavirus Treatments to Watch - Secular Sanity - Apr 11, 2020

(Apr 10, 2020 04:45 PM)Zinjanthropos Wrote: Does it mean that Covid patients are also dying of stroke or cardio related problems and not just pneumonia? Do we know those percentages if so?

That’s what they suspect but no one really knows yet, Zinman. Everything is still up in the air.

Many COVID=19 Patients are Dying From Cardiac Arrest

Doctor Gambles on Clot Busting Drug to Save Virus Patients

Stroke Drug Could Help Covid-19 Patients

Fear of the unknown: One fear to rule them all?

The oldest and strongest emotion of mankind is fear, and the oldest and strongest kind of fear is fear of the unknown.—H. P. Lovecraft

11 Ways Emotionally Intelligent People Overcome Uncertainty

I struggle with #1 and #10. 

I don’t want to wait until the tiger cougar shows up. I’d rather look for patterns and avoid the cougar altogether and "what ifs" have always been a problem fro me. 

1. They quiet their limbic systems

In other words, they tell their limbic system to settle down and be quiet until a hungry tiger cougar shows up.

10. ...but they don’t ask, "What if?"

Successful people know that asking "what if?" will only take them to a place they don’t want, or need, to go to.



RE: Experimental Coronavirus Treatments to Watch - Zinjanthropos - Apr 11, 2020

(Apr 11, 2020 03:51 PM)Secular Sanity Wrote:
(Apr 10, 2020 04:45 PM)Zinjanthropos Wrote: Does it mean that Covid patients are also dying of stroke or cardio related problems and not just pneumonia? Do we know those percentages if so?

That’s what they suspect but no one really knows yet, Zinman. Everything is still up in the air.

Doctor Gambles on Clot Busting Drug to Save Virus Patients

Hmmm. Hope someone is keeping stats. Would be good to know survival rate of people already prescribed/taking a blood thinner.