Important Covid-19 Discovery - with Dr. George Tetz | The Empowering Neurologist EP. 96
In this episode of The Empowering Neurologist, Dr. David Perlmutter interviews Dr. George Tetz, co‑founder of the Human Microbiology Institute, about a newly submitted manuscript that analyzes the SARS‑CoV‑2 proteome. Dr. Tetz reports the first identification of prion‑like domains (PLDs) in two viral proteins: the spike (S) protein’s receptor‑binding domain and the nucleocapsid (N) protein’s N1A/N1B regions. He explains that homologous PLDs are also present in the human ACE2 receptor’s α‑1 helix, suggesting a direct PLD‑mediated interaction that may enhance viral tropism beyond the lungs, contributing to high transmissibility and multi‑organ involvement. The nucleocapsid PLDs appear to bind viral RNA, and disrupting this interaction could block virion assembly, offering a novel therapeutic target. Dr. Tetz proposes anti‑prion strategies—drugs that prevent protein misfolding—as a potential avenue for COVID‑19 treatment, though his lab is currently operating remotely. The conversation expands to the broader microbiome context: Dr. Tetz’s prior work on bacteriophages in neurodegenerative disease, the hypothesis that a diverse gut microbiome may modulate COVID‑19 outcomes, and the speculative idea that phage‑based interventions could influence disease progression. Both hosts acknowledge the urgency of rapid, pre‑print publishing during the pandemic and the need for interdisciplinary research to connect viral protein biology, host microbiome, and clinical outcomes.
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Well, hello everyone. Dr. David Perlmutter here. Welcome again to The Empowering Neurologist. We have in the past interviewed Dr. George Tetz. He has done some incredible research looking at what are called bacteriophages and the potential role that they may be playing in things like Parkinson's disease. He's now working with the COVID-19 genome and has some very interesting things to tell us today about what he's learned and a paper that he has coming out using that information. Let me tell you a little bit about George. He is an MD-PhD and is the co-founder of the Human Microbiology Institute in New York. He is— his research focuses on the role of microorganisms in neurodegenerative diseases, and cancers. And in fact, he has published some information that indicates that there is the suggestion that Alzheimer's may be caused by a transmissible agent. His latest research, for the first time, have shown that the bacteria that he's talking about can actually trigger the misfolding of the proteins that we know is One of the things that's involved in Alzheimer's models, and as such, this may be a target for new interventions. He's also done studies in, as mentioned, how these bacteriophages may play a role in Parkinson's, that is how they affect the gut microbiome, and then secondarily how that may lead to a variety of chronic human inflammatory conditions. He— his recent findings show that bacteriophages may be in fact playing a role in Parkinson's and even type 1 diabetes and what we've learned to call the leaky gut syndrome, the important role of bacteriophages. So we've talked about that before, and in fact, Dr. Tetz has written a chapter in The Microbiome and the Brain that I edited. I edited the book, not the chap— well, I edited the chapter too, that's for sure. And that said, though, he's going to jump right in at this point and tell us what he has learned with reference to this coronavirus issue. Well, hello, George. It's really good to see you again.
Nice to see you, David.
You were— we had a phone call, I guess it was yesterday, and you were really having some excitement about some research that you have coming out with reference to COVID-19. Where do we start?
Sure. I don't know. We can start very briefly with— I think I would like maybe to start that today it is obvious that the COVID-19, the disease that is caused by the virus named SARS-CoV-2, according to the right name classification, is really something new. It is very important, I believe, just for all of us right now to follow some of the very, very easy directions that actually we're guided right now by the government and actually to keep all these protective measures that will aim to help not only the individual, all of us, but also the whole community and will give additional gap and additional time for the medical system to get better prepared and to avoid such a disaster and terrible situation that happens right now in some European countries when people simply run out of crucial medical equipment such as ventilators. It is the first part, but the most important thing I think is that we are very excited with our latest discovery that we have just submitted an hour ago, helping us to dig a little bit deeper into the nature of COVID-19 disease and figure out why it is so deadly and what is its principal difference with all existing coronaviruses that are known today.
And so this is new information. I'm getting ready to write, write down what you're talking about. This is what was actually going to publication today from your laboratory. Right, exactly. How do we break it down?
Sure. I would be more than happy just maybe very briefly to guide you through this discovery. Does that make sense?
Yeah, I think that'd be a terrific idea. Let's talk about discovery and then— Sure. Open it up to what it may mean, how we leverage the information.
Good. So I will start that the first draft of this manuscript, it was ready by March 17th. We started our manuscript with some statistical data. By March 17th, the number of people who were infected with COVID-19 was around 180,000 patients, with around 7,000 people who died by that time. Today, as we mentioned, we submitted a paper an hour ago. I had to change these numbers. And as of today, there are over 300,000 patients with COVID-19 and over 15,000 patients already died. So, it literally doubled in 6 days. So, it is developing very, very fast and very quickly, actually even quicker than it was predicted in the beginning. So, I will try not to become too academic, but these days, you know, I can promise nothing. So, why has the coronavirus been so successful? Why is it behaving in such an extreme way? So, to address the question in our work, we dig deep into the viral structure and analyze the viral proteome, or the viral proteins. that actually the viral particle consists of. We analyzed and compared it with other coronaviruses that are known today. The short answer is that within its viral structure, we have discovered novel vaccine and novel therapeutic targets that might contribute to the development of novel targets for the whole medical community. And we figured out the certain proteins that actually might contribute why the virus enhances the lung fibrosis so aggressively. So, the long answer is that we have discovered for the first time that within the viral proteins, there is a number of proteins that do have the prion-like domains. Yes. Again, we're talking about the prions. So, what is a prion? Prion is a protein, right, that is an infectious agent itself, and it has a very particular conformation. So, once the prion protein contacts with another protein, the normal one, it changes its structure. It changes its conformation, triggering the appearance of the new prions. Once the number of prions accelerates, they form so-called misfolded prion aggregates that disrupt the normal cell function and normal work of tissues and organs. Moreover, the prion cascade is the primary reason for the development of different neurodegenerative diseases. A couple of years ago, we have published a number of articles where we analyzed millions and millions of viral proteins and figured out that the number of viruses that have in their structure the prion-like domains within their proteins. After our analysis, we figured out that these viral— that the prion-like domains within these viruses. They're essential elements for the interactions between viral— between the viral particle and human cells. So, in this, our latest work, it was the most detailed analysis of the SARS-CoV-2 proteins, and we found out that compared with other coronaviruses, you do have the prion-like proteins in 2 of its structures. The first one is the spike protein.
Spike, absolutely.
Right. So, if you will imagine, right, the viral particle, a viral particle is a circle one with a number of protrusions that actually are— that form some sort of crown. That is why it is named crown-like Sorry, that is why it is named coronavirus. And we found out that within the surface of each spike, there is a prion-like domain. So, we dig deeper and figured out that the prion-like domains are localized within receptor binding domain of its spike. So, next we analyzed the receptor on the human cells. for this virus. The receptor is named ACE2, and we could not believe our eyes. Within alpha-1 helix of ACE2 receptor, we also found prion-like domains, and according to our analysis, amino acids within prion-like domain of— within the viral spike interact with amino acids Within prion-like domains on our host cells.
Oh, this is really too much. I mean, that, that, uh—
Sorry?
It's really, it's really hard to imagine that on the ACE2 receptors that you've just found these prion-like domains and they're similar to what you're seeing on the spike protein.
Exactly. They are not identical. They are not identical. They're homologous, but they have not to be identical.
They're homologous, and that— it's quite a smart virus this time around, isn't it?
It is. And actually, once we analyzed the presence, you know, of prion-like domains within the spike protein compared with other coronaviruses, for example, very close relative SARS-CoV-2, virus or MERS virus, there are no prion-like domains within spike protein in these viruses. So, actually, we believe that it is one of the reasons why SARS-CoV-2 actually interacts with a lot of human cells, excluding actually the lung cells, because it was shown to have a very high tropism for other cells, the liver and kidneys and in other cells within our tissues. It actually be one of the important things actually that might contribute for its high transmission rate and for its very high number of off-target effects when the virus attacks cells also outside the lungs.
So, this isn't just the next-gen coronavirus, is it? I mean, it's been looked upon as, well, we had SARS, we had MERS, now we have this one. And, you know, it just sort of looks like it's a progression. But what you've identified really is quite a different experience, isn't it?
It is. What's more, we analyzed and figured out, found out that the prion-like domains are also localized within the nucleocapsid protein. That is an internal protein that is located inside the virus. And the role for this nucleocapsid is that it has to bind to viral RNA and is required for the viral progeny assembly within human cells. We found the presence of these prion-like domains in the very specific regions of N protein named N1A and N1B, therefore pointing out that these prion-like domains do interact with viral nucleocases. Actually, it fits perfectly well with our last article that was recently published. I guess I sent I sent it to you. It was published in Nature Scientific Reports showing that microbial DNA actually binds to the prion-like proteins leading to the cascade of prion-like alterations in Alzheimer's disease. But the bottom line is that in this work, we got the same results that nucleic acids can bind tightly with the proteins that do have a pre-Like domains. But along with their just, you know, interesting scientific data, it has a very important translational potential. I will tell you why, because as for now, the nuclear capsid protein, it is not broadly used, you know, for the— it is not broadly used neither as a drug target or as a vaccine target. So, it is not really used in the drug development. And according to our data, we believe that the prevention of this prion-like aggregation or prion-like interaction between nucleocapsid and viral RNA can lead to the prevention of the formation of new viral particles.
So, that's a key step then in the viral replication that might be then available as a target. How would you target that step?
It's a good question. We have just received this data and these results, but our laboratory unfortunately is shut down. You see, I'm talking from home. Hopefully, the situation will be changed within a couple of weeks, but right now all of us, we work remotely and we have a lot of bioinformatic analysis, so the work has not stopped. The good thing is that our discoveries for both spike protein and for nucleocapsid actually opens the discussion for the use of so-called anti-prion strategy. The whole range of anti-prion drugs aim to prevent the protein misfolding and/or protein-like misfolding that actually leads to the to the certain conformational changes. I don't know how to simplify it. So, we'll hopefully, we will get some positive results and we'll be able to share some of our new thoughts pretty soon.
Is there any possibility of utilizing, utilizing some of this phage therapy or to Interact here in some way?
Actually, the bacteriophage therapy is not used for the treatment of viral diseases. If we're talking about more speculative ways, based on our latest articles, I can easily assume that the use of certain bacteriophages with the presence of prion-like domains on their surfaces might have somehow contributed to the amelioration of the progression of the disease, but we have not tested it.
Let me tell you where I'm going with this and why I bring it up. I just published a brief review of the consideration of the role of the microbiome in possibly the pathogenesis of this viral infection. When we look at the incredibly low rates in sub-Saharan Africa and places like Haiti, where they have a more diverse, robust, if you will, microbiome, it seems that there is at least a consideration, at least on my part, that the microbiome might be mediating some of their resistance or their better outcome as it relates to immune function and inflammation. So that's the reason I I wanted to tickle you a little bit with this idea of phage technology in that you've done this work previously with reference to phage in the microbiome.
Well, if to talk through my microbiome lens, definitely that makes sense what you are talking about. If we will, on the other hand, well, if we will take a look for the statistical analysis of what happens right now, for example, in Italy, one will see that the majority of people who die, right, they do have certain underlying conditions such as oncology or other diseases of respiratory tract like COPD and so on and so forth. So, you know, in order to get into more details linking the microbiome COVID-19, I think it is necessary to take a look from different perspectives. What is the structure of other populations? What is the number of underlying disease in their populations? However, there are a lot of works showing the role of microbiome, for example, in the development of COPD. So, well, everything is like The question, you know, how to, how to complete this puzzle, how to put the puzzle together.
Yes. And, you know, when you look at the, the multitude of so-called underlying conditions, including a BMI greater than 40, I might add, uh, and the others— coronary heart disease, type, uh, type 2 diabetes, um, obviously immunosuppression— uh, many, many of these things do in fact have disturbances or dysbiosis of the gut bacteria. I'm wondering if it were possible to explore that and to try to determine if there's anything unifying about all of these risk individuals in terms of their so-called underlying disease. There are plenty of diseases that people have that don't necessarily bode for a bad outcome as it relates to this infection. So one would wonder if this, you know, if we circle back to where we all— where you and I began our relationship, you know, a couple of years ago.
It's a very interesting idea. And once again, I really appreciate it. And it is, I think— well, I would actually— I would like maybe even to diversify it a little bit. Because hopefully, right, the COVID-19 will decrease one day and hopefully, you know, it will not become some sort of seasonal flu around the globe. But anyway, there are a lot of other human diseases including the regular flu or a lot of other coronaviruses. They are not so deadly and they, you know, they're known as a common cold. But the role of microbiome and the role of microbiome and underlying conditions in the development and in the progression of these diseases among some people is a very important question. Well, let's take a look. Generally, from the regular flu or from influenza, over 600,000 people are dying Annually worldwide. So the question, right, how the microbiome plays role in these very common viral infections, I think it is very, very fair question, and it is very fair direction and very interesting direction to uncover why someone are dying, why some are not, and what is the role for microbiome, what is the role for the disrupted disrupted the intestinal barrier. So there are a lot of questions that have to be addressed.
Yeah. And, you know, when you look currently, as in today, and here we are, it's March 23rd, 2020, at the global distribution, I think that, you know, obviously travel and tourism has a lot to do with it. Trade has a lot to do with it. But you do see challenges to that notion or those notions in that Certain areas that do have— that are very population dense, and yet are not as involved in hygiene as we are, seem to be having a better go of it. So one wonders if, you know, this hygiene hypothesis of Dr. Strachan back in 1988 might have some validity here, that, you know, there's good to challenging the immune system with not as hygienic an environment. Yeah.
Well, it's 100% true because it's necessary to tickle, it's necessary to challenge your immune system, it's necessary to train it. Thus, it will be, you know, thus it will respond much better for different challenges, including the viral ones. So, I agree with you that, you know, such a statement can be further discussed and further studied. But anyway, you know, the people with a better immune response are less likely, you know, to really develop this disease just because it will be— the organism is struggling, our organisms are struggling with the viral part, with viruses every time, every day. And so, of course, people with a better functioning immune system would be in much more preferable position. And there are a lot of works linking the hygiene, hyperhygiene with a normal immune response or with the formation of immune system. Yeah.
Well, listen, I'm hopeful that you and I can touch bases again sometime soon and we can hear more about what you're doing. And hopefully that can be translated. I mean, it's really breathtaking, you know, and to look at it, how these sequences are shared between the organism and its, you know, human receptor sites. It's spooky to think how sophisticated this virus really is.
It is. I will send you the link very soon.
Great.
At least for the preprint. Hopefully it will be accepted to the peer-reviewed journal also. Oh,
I'm sure it will be.
Yep.
We're seeing a lot of publications now that aren't necessarily peer-reviewed but are expedited, and I think that, you know, if you're able to tease through them, I think that's probably a good idea, you know, so we don't have the, you know, 6 weeks delay at the early—
Oh no, of course. And right now when we prepared these articles, there are a lot of really great Great studies that are right now just still to be on the waitlist for many journals. But you know, right now I think the scientific community you know has no time to wait for everything to be peer reviewed. That's for sure. All right.
Well, listen, thank you for your time, and I hope we get to see each other again soon.
Thank you very much. Have a good day. Thank you.
Bye for now. Bye. Well, again, thanks to Dr. George Tetz. He is the co-founder of the Human Microbiology Institute. Institute in New York City. We wish him well in New York City and really grateful for his pioneering research. You know, everybody's contributing something along the way, and hopefully we can solve this, this challenge. I'm Dr. David Perlmutter. Thanks for joining me here on The Empowering Neurologist, and I'll be back soon. Bye for now.
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