Tag Archive for: ACE2 receptor

Using Melatonin to Treat COVID-19

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Today’s research paper is a type of study that uses large datasets to examine the relationship between successful treatments for people with COVID-19 and related viral infections. Let’s take a look.

Network-Based Drug Repurposing

To say that this is complicated is a tremendous understatement, but let’s give it a go. Researchers identified specific targets for the many different strains of COVID and SARS viruses, including all of the research on the receptor targets in the body for every COVID-related virus, such as the ACE2 receptor. Then they examined each drug that has been used to treat people with the virus to see how effective it was, along with drugs that had specific receptor targets when used for other reasons. Researchers weren’t looking for a cure; they wanted to determine whether specific symptoms in various parts of the body improved such as the lungs, the heart, fatigue, etc.

They started with dozens of receptors and over 2,000 FDA-approved medications, and after running the initial analysis, they reduced the number of drugs to 135. They ultimately came up with three pairs of medications that could be effective in treating COVID-19: sirolimus plus dactinomycin, mercaptopurine plus melatonin, and toremifene plus emodin. I would wager that five of those are medications you’ve never heard of, but you’re probably acquainted with melatonin. That’s what caught my attention, so let’s take a look at why melatonin would be included in a potential treatment for COVID-19.

Melatonin as an Antiviral

In their explanation, researchers said melatonin has been reported to have a potential for treating antiviral infection because of its anti-inflammatory and antioxidant effects. As suggested, melatonin can indirectly impact the ACE2 receptor, which is a key target of the COVID-19 virus. Mercaptopurine blocks specific papain-like proteases such as the ACE2 receptor; the hope is that the combination will block the ACE2 and other target receptors from the virus and reduce the inflammatory response.

The Bottom Line

The researchers say there’s a long way to go before this combination can be used to treat COVID-19—pre-clinical and clinical trials for sure to test whether this combination actually works to treat the virus.

When it comes to melatonin, it makes sense to add it to our immune-boosting regimen. Its mechanism of action is different from the zinc, vitamin D, and vitamin C we may already be taking. The question is how much? I don’t have a specific answer because there’s still so much research to review. But I’m going to begin with 6 mg. That’s not too much and even if it doesn’t work for immune boosting, the potential benefits for memory, etc., make it worth taking; take it at night, of course, because of its ability to help you sleep. When I’ve reviewed more research, I may be able to give you a more definitive answer. In the meantime, there’s no apparent downside to taking melatonin. If you feel you need the additional immune boosting—and who doesn’t—give it a try.

What are you prepared to do today?

        Dr. Chet

Reference: Nature. https://doi.org/10.1038/s41421-020-0153-3

COVID-19 and Blood Type

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This week we’ll examine reports about comorbidities and other factors associated with the severity of the COVID-19 virus. We’ll begin with a question from a long-time reader and family member who shares DNA with Paula: her brother, Steve. Both have blood type A, which has been in the news as a factor in the severity of COVID-19.

The study that got the most attention was published in the New England Journal of Medicine. It was an observational study, which is important. They didn’t select a group of people with specific genetic mutations for the ACE2 gene and the ABO gene, which determines blood type, and then give them the virus; no ethics committee in the world would approve that study. Instead they collected patient data from the hardest-hit areas in Spain and Italy, including tissue or blood samples. They had limited historical data on the patients, especially known comorbidities such as heart disease, high blood pressure, and type 2 diabetes. They also knew the severity of the disease for each patient, including who was on oxygen and ventilators. It should be noted that about 80% of the most severe cases were people with comorbidities.

The researchers analyzed the entire genome of each patient and the control subjects, people from the same geographical area who didn’t get the virus. That worked out to 1,600 with the virus and 2,200 controls. To analyze every gene with potential mutations requires an average of 8.5 million combinations per person. They found two mutations or SNPs (single nucleotide polymorphisms) that seemed to increase the risk of a severe case of the virus: one area was responsible for blood-type proteins and the other for specific proteins use by the ACE2 receptor. They found that people with blood type A were 45% more likely to get a severe case of the virus requiring oxygen or a ventilator; people with type O blood had a 35% lower risk of the same response. They don’t know yet what the ACE2 protein area SNPs mean.

What does that mean in the real world? As this research continues, they may be able to determine a profile for a person most at risk so that they can get preventive treatment (if one is developed) and early treatment upon diagnosis. What I don’t think it means is that those with blood type A are at greater risk of catching the virus or type Os are at less risk of catching the virus, but I’d recommend that blood type A people should be even more diligent in reducing their exposure, and if they suspect they are infected, seek treatment earlier, rather than later.

Insider Conference Call

The Insider Conference Call is tomorrow night at 9 p.m. Eastern Time. Besides answering questions, I’ll report what I’ve learned about a Texas physician who claims to have found the “silver bullet” to cure COVID-19. You can become an Insider up through 8 p.m. and still participate live.

What are you prepared to do today?

        Dr. Chet

References:
1. https://bit.ly/3gX1Bmh
2. NEJM. 2020. DOI: 10.1056/NEJMoa2020283.

COVID-19 Attacks the Whole Body

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Our look at diseases associated with COVID-19 continues in this pre-4th of July memo. Let’s turn to diabetes. We know, based on prior reports, that people with type 2 diabetes as well as other comorbidities are susceptible to getting the worst symptoms of COVID-19. But now, there are also some reports that COVID-19 infections may cause diabetes; people diagnosed with COVID-19 with minor symptoms have developed type 1 diabetes later.

How could that happen? The first way may be a direct attack on the pancreas because it also contains many ACE2 receptors. Or it may be that as the virus stays in the body, it triggers an autoimmune response. Or it may somehow stimulate other dormant viruses due to the inflammation and immune response.

One of those is the Epstein-Barr virus; almost 90% of us have been exposed to it. Epstein-Barr impacts the nervous system in a significant way. Perhaps the challenge to the immune system somehow triggers the activation of Epstein-Barr to cause neurological dysfunction from mild to severe.

In doing the background research for these Memos, I found that scientists are looking at every organ for potential consequences of the COVID-19 virus infection. We already knew of cardiovascular problems as well as kidney damage; lung damage was significant whether the patient was on a ventilator or not. The impact on blood vessels, which are full of ACE2 receptors, are the root cause of many of the problems. With the loss of taste and smell, it may be that the virus causes the death of enough of those organelles that we are permanently impacted. We’re learning some patients develop problems in their brains such as strokes, psychosis, and altered mental state, and we’ll discover more conditions that are impacted by the virus as time goes on. And we haven’t even begun to discuss the microbiome.

The Bottom Line

As I wrote several weeks ago, I don’t want you to fear this virus but you’d better respect it. That means you do your best to avoid getting it and avoid spreading it.

This is the beginning of the major holiday of the summer. Being restricted in what we can do and where we can go has worn on people, perhaps even you. So let me leave you with two thoughts.

First, if getting into a pool is part of your holiday plans, go ahead. The chlorine in a well-maintained pool or hot tub will kill the virus and sunshine helps, so have some fun; but if you’re just socializing while wet and not social distancing, wear a mask.

Second, I’ll finish where I began this series: with wearing a mask in public. You don’t have to like it. Who does? Science clearly shows it reduces the risk of catching or spreading the virus which, as we’ve seen, has far more implications then just a little fever and cough. So if you’re going into public places, do what I do and wear the damn mask. Please.

What are you prepared to do today?

        Dr. Chet

Reference: Nature. 2020. doi: 10.1038/d41586-020-01891-8.

COVID-19 and the Small Intestine

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With the ACE2 receptor implicated in the long-term side effects of COVID-19, let’s begin with the digestive system. The gastrointestinal distress such as cramping, pain, and diarrhea are obvious, but there are reports that some people have had to have their entire small intestine removed due to damage from the COVID-19 virus. How could that happen?

One of the characteristics of these specific cells that contain the ACE2 receptor is that they function to absorb nutrients. If the virus interferes with absorption of nutrients by cells, the first cells that will be impacted are in the small intestine; it could literally starve to death. Second, a significant blood supply goes to the digestive system. We know that the COVID-19 infection can cause unusual clotting; if the blood flow is restricted to the small intestine, that could also cause cell death.

While we’re not done with this topic yet, I think it should be clear that we don’t know as much as we need to about the long-term effects of COVID-19. That’s why it’s so important for research to continue and for all of us to be vigilant in protecting our own health and the health of everyone we encounter.

Because of the holiday weekend, we’ll complete this tomorrow, but the discussion is far from being over as more research reveals more issues from exposure to this virus.

What are you prepared to do today?

        Dr. Chet

References: www.rndsystems.com/resources/articles/ace-2-sars-receptor-identified

ACE2 Receptors: Gateway for COVID-19

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The number of cases of COVID-19 continues to rise and rise and rise. As restrictions on shopping, dining, and entertainment have been reduced, and then sometimes reinstated, the debate over which businesses should be open, social distancing, and even whether to wear a mask continues. Let me make it simple for you: wear your mask to protect others from you and you from them. Period.

There has also been a tremendous rise in the research on COVID-19, specifically, the short-term and long-term effects of the virus on the body. This virus is different from others; it isn’t as simple is getting the flu or a severe cough, and then life returns to normal after a week or so. Research is finding some significant long-lasting effects on the body. The locations impacted seem to contain high numbers of the ACE2 receptor, the receptor used by the virus to enter our cells. We already knew the sinuses, lungs, and adjoining blood vessels contain significant numbers of ACE2 receptors as well as the kidneys.

Researchers for a data analytics company examined every published paper, over 100 million of them, to find out where ACE2 receptors have been found and then performed an analysis examining every potential interaction, over 45 quadrillion of them. They found that there are significant numbers of receptors on the tongue, the nasal passages, and the ciliated passages to the lungs. The most significant find was the enterocytes that line the small intestine. That means that should the virus get to those locations, it can potentially wreak havoc there. We’ll talk about some of the organs and systems that have been impacted by COVID-19 the next two days.

What are you prepared to do today?

        Dr. Chet

Reference: eLife 2020;9:e58040 DOI: 10.7554/eLife.58040