COVID-19 spike protein vs. vaccine spike protein: key differences | Dr. Rhonda Patrick
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There are about 26 spike proteins on the surface of each SARS-CoV-2 viral particle that help the virus enter and infect cells. The spike protein binds to the ACE2 receptor and undergoes a conformational change from a closed or pre-fusion conformation to an open or post-fusion structure (as it fuses with the cell membrane). Some people surmise that if the viral spike protein is dangerous — because it allows the virus to enter cells — then vaccine-related spike proteins render vaccines unsafe. COVID-19 vaccines contain different spike proteins than the SARS-CoV-2 virus. All vaccines used in the United States contain two extra amino acids that lock the spike protein into the prefusion conformation, such that it cannot fuse with the cell membrane. In this clip, Dr. Rhonda Patrick describes what distinguishes viral spike proteins from vaccine-related spike proteins.
Kyle: Okay. Well, Dr. Patrick, this next question's for you, and it's about spike protein. We know that the spike protein can be dangerous and cause a significant immune response, and there's this idea floating around that because spike protein is dangerous from the SARS-CoV-2 virus, therefore, the COVID-19 vaccines must be as dangerous as well. What are your thoughts on that?
Dr. Patrick: Well, I have a lot of thoughts on that, Kyle. I've thought long and hard about it. But sort of before I get into some of the details, I think, the spike protein has really become a common household name. At this point, most people around the world know what the spike protein is mostly because it's the entry point for the SARS-CoV-2 virus to get into our cells. There are about 26 different spike proteins. I shouldn't say different. There are about 26 spike proteins that line the surface of a SARS-CoV-2 viral particle, and these spike proteins will bind to a receptor on many different cell types we have in our body that have a receptor called ACE2. And when the spike protein then binds to the ACE2 receptor, it undergoes a conformational change that essentially refers to the structure of it changes. So it binds on to this receptor, and it then elongates, and sort of twists and turns around, and then it fuses with the cell membrane and is, you know, engulfed inside of the cell. Another way it happens is through endocytosis. But essentially, the point I want to make here is that conformational change happens because when the spike protein initially binds to the ACE2 receptor, it's in a conformation called the pre-fusion conformation. You can think of it more like a closed type of conformation. Once it binds, this triggers a conformational change for it to, again, like I said, elongate and sort of twist around. When it does that, that is referred to as the post-fusion conformation. And the reason that's really important is because all of the vaccines that are available in the United States under either emergency use authorization or under FDA authorization or up and coming vaccines, so that includes the Moderna and the Pfizer-BioNTech mRNA vaccines, the Johnson & Johnson adenoviral vaccine, as well as the Novavax vaccine, they all contain an insertion of two proline amino acids into the spike protein to lock it into the pre-fusion conformation. And this was brilliant work done by the structural biologist, Dr. Jason McLellan. He's at the University of Texas in Austin. And he thankfully had figured out this way to lock viral proteins into the pre-fusion conformation. First it was with the respiratory syncytial virus, RSV, and then later, he had figured out for the other beta coronavirus, the MERS coronavirus. And so he really had a running start there. And the reason that is so important is because, when you're comparing the spike protein from the SARS-CoV-2 virus, as I mentioned, there's 26 of them on every viral particle, to the spike protein that is in the vaccines, including the mRNA vaccines and the vaccines in the United States, it's a different spike protein. It's a spike protein that cannot undergo that structural change. It does not elongate and, you know, dig into the cell membrane and fuse with it. It's a different spike protein because of those two proline amino acids that were inserted to lock it into the pre-fusion conformation.
And one of the first things you learn as a scientist, as a budding young scientist is that you can't compare apples to oranges. You can't compare two different things. You have to compare apples to apples or oranges to oranges. And so when you're talking about a different spike protein, structurally, it's different, right? You can't take a study that's looking at the spike protein that is from the surface of SARS-CoV-2 and say everything that that spike protein is doing applies to the spike protein in the vaccines that are available in the United States because it's different. And so, I think, that's a really, really upfront important thing to understand. And the burden of proof is on, you know, people making the claim that the spike protein from the mRNA vaccines is dangerous because some studies have shown that the spike protein from the SARS-CoV-2 by itself can be dangerous. You have to show that, and it has not been shown. So, what these studies that have shown that the spike protein from SARS-CoV-2 virus, how it can be dangerous, there's been some in vitro studies, which means cells in culture in a dish. When you dump spike protein on them, it can cause the activation of cell signaling pathways that could lead to cell death. This is often referred to as cytotoxicity. There's also been some animal studies shown where either recombinant protein, which is just basically made in a lab, so they make the spike protein, or what's called pseudovirus expressing the spike protein, so this is not the SARS-CoV-2 virus, but it sort of acts like a virus to allow it to get into cells, if you directly inject the pseudovirus with a spike protein into the trachea of hamsters, it causes severe lung damage and also gets into the circulation and causes circulatory damage and vascular damage to the vascular system.
And so these studies, and there's been, you know, a few of those, have really spurred this idea that the spike protein from the vaccines must be dangerous because these studies showing the spike protein that's found on the surface of SARS-CoV-2 is. And again, you can't compare. You can't make that comparison, and that's really just one aspect of, you know, this story. The other aspect has to do with where the spike protein goes in the body. And, you know, I think, first and foremost, anyone that's concerned about these studies showing that the spike protein by itself is dangerous should be terrified about getting SARS-CoV-2 because, for one, you're getting, as I mentioned, 26 of those spike proteins on one viral particle. How many viral particles are replicating inside of your cells at any given moment? You know, thousands of them. And on top of that, there have been studies that have shown that SARS-CoV-2 virus is detected in multiple organs. You know, this isn't just in the nose and in the trachea and in the lungs, which in and of itself is bad. I mean, the damage to your lungs is, you know, one major concern. But the SARS-CoV-2 virus, again, with spike protein has been detected in the heart in humans. It's been detected in the brain. It's been detected in cerebrospinal fluid. It's been detected in kidneys. It's been detected in the GI tract. It's been detected in the testes. It's in many different tissues in humans. Oh, and it's been detected in plasma in the circulatory system. So, again, you know, the concern should be amplified for actually contracting the SARS-CoV-2 virus if you are concerned about the study showing spike protein itself is dangerous.
A protein that plays a critical role in regulation of blood volume, systemic vascular resistance, and cardiovascular homeostasis. ACE2 is present on the cells of many organs in the human body, particularly those of the lungs, arteries, heart, kidney, and gastrointestinal tract, and is a critical element of the renin-angiotensin biochemical pathway. SARS-CoV-2, the virus that causes COVID-19, exploits the ACE2 receptor to gain entry into cells.
A group of related viruses that cause illness in birds and mammals, including humans. Members of this group include SARS-CoV-1 (which causes severe acute respiratory syndrome, or SARS), MERS-CoV (which causes Middle East respiratory syndrome, or MERS), SARS-CoV-2 (which causes COVID-19), and HCoV-OC43 (which causes the common cold).
An infectious disease caused by the novel coronavirus SARS-CoV-2. COVID-19, or coronavirus disease 2019, was first identified in Wuhan, China, in late 2019. The disease manifests primarily as a lower respiratory illness, but it can affect multiple organ systems, including the cardiovascular, neurological, gastrointestinal, and renal systems. Symptoms include fever, cough, fatigue, shortness of breath, and loss of smell and taste. Some infected persons, especially children, are asymptomatic. Severe complications of COVID-19 include pneumonia, sepsis, acute respiratory distress syndrome, kidney failure, multiple organ dysfunction syndrome, and cytokine storm. Treatments currently involve symptom management and supportive care. Mortality varies by country and region, but approximately 6 percent of people living in the United States who are diagnosed with COVID-19 expire.[1] 1
Experiments that are performed using cells or microorganisms outside of their normal biological context and are often done in a test tube or petri dish.
An essential mineral present in many foods. Iron participates in many physiological functions and is a critical component of hemoglobin. Iron deficiency can cause anemia, fatigue, shortness of breath, and heart arrhythmias.
A respiratory illness caused by the MERS-CoV coronavirus. MERS is a zoonotic illness, first isolated in bats and then transferred to camels and humans. Symptoms may be mild, moderate, or severe, and include fever, cough, diarrhea, and difficulty breathing.
A chemical that causes Parkinson's disease-like symptoms. MPTP undergoes enzymatic modification in the brain to form MPP+, a neurotoxic compound that interrupts the electron transport system of dopaminergic neurons. MPTP is chemically related to rotenone and paraquat, pesticides that can produce parkinsonian features in animals.
A type of vaccine that contains the genetic material to encode a single viral protein that, when injected into the body, induces antibody production against the target protein. Because mRNA degrades easily, it must be encapsulated in lipid nanoparticles in order to be absorbed by cells and often must be delivered in multiple injections to promote optimal immune response.
The virus that causes severe acute respiratory syndrome, or SARS. First identified in China in 2002, SARS-CoV-2 is a type of coronavirus. It was responsible for an epidemic that killed nearly 800 people worldwide.
The virus that causes COVID-19. SARS-CoV-2 is one of seven coronaviruses known to infect humans. Others include SARS-CoV-1 (which causes severe acute respiratory syndrome, or SARS) and MERS-CoV (which causes Middle East respiratory syndrome, or MERS). SARS-CoV2 exploits the angiotensin-converting enzyme 2, or ACE2, receptor to gain entry into cells. The ACE2 receptor is widely distributed among the body's tissues but is particularly abundant in lung alveolar epithelial cells and small intestine enterocytes. SARS-CoV-2 binds to a cell's ACE2 receptor and injects its genetic material (RNA) into the cytosol. Once inside, the viral RNA molecules are translated to produce RNA-dependent RNA polymerase, also known as replicase, the enzyme critical for the reproduction of RNA viruses. The viral RNA is then packaged into infective virion particles and released from the cell to infect neighboring cells.
A type of white blood cell that plays critical roles in the body's adaptive immune response. T cells form in the bone marrow but mature in the thymus (hence the "T" designation). They destroy malignant cells by triggering apoptosis – a type of cellular self-destruct mechanism that rids the body of damaged or aged cells.
The highest level of intake of a given nutrient likely to pose no adverse health effects for nearly all healthy people. As intake increases above the upper intake level, the risk of adverse effects increases.
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