COVID-19 – causing death by cutting off oxygen and oxidation of the lungs?
Steve’s post that linked to a piece on Medium I would now label as cutting edge – the first time I had seen the angle that COVID-19’s real attack is to free up the iron ion located within the heme molecule that binds oxygen into the heme (e.g., hemoglobin) within your red blood cells.
No oxygen mean hypoxia – oxygen starvation like what jet fighter pilots get when their O2 machines fail or hikers get when above 10,000 foot climbs.
Except you’re in a hospital bed and no amount of air pressure from a ventilator pumping O2 into your lungs can fix. Which, sad to say, is useless – the ventilator pressure hurts the aveoli sacs in your lungs (that actually do the gas transfer of O2 in and CO2 out) and there’s nothing in your blood stream to pick up that O2 anyways.
Grokster Mike then found this PDF that went more scientific – an abstract (emphasis mine and reformatted a bit):
No oxygen mean hypoxia – oxygen starvation like what jet fighter pilots get when their O2 machines fail or hikers get when above 10,000 foot climbs.
Except you’re in a hospital bed and no amount of air pressure from a ventilator pumping O2 into your lungs can fix. Which, sad to say, is useless – the ventilator pressure hurts the aveoli sacs in your lungs (that actually do the gas transfer of O2 in and CO2 out) and there’s nothing in your blood stream to pick up that O2 anyways.
Grokster Mike then found this PDF that went more scientific – an abstract (emphasis mine and reformatted a bit):
COVID-19: Attacks the 1-Beta Chain of Hemoglobin and Captures the Porphyrin to Inhibit Human Heme Metabolism
liu wenzhong, Li hualan
Submitted date: 28/03/2020 • Posted date: 30/03/2020
Licence: CC BY-NC-ND 4.0
Citation information: wenzhong, liu; hualan, Li (2020): COVID-19: Attacks the 1-Beta Chain of Hemoglobin
and Captures the Porphyrin to Inhibit Human Heme Metabolism. ChemRxiv. Preprint.
https://doi.org/10.26434/chemrxiv.11938173.v5The novel coronavirus pneumonia (COVID-19) is an infectious acute respiratory infection caused by the novel coronavirus. The virus is a positive-strand RNA virus with high homology to bat coronavirus. In this study, conserved domain analysis, homology modeling, and molecular docking were used to compare the biological roles of certain proteins of the novel coronavirus. The results showed the ORF8 and surface glycoprotein could bind to the porphyrin, respectively. At the same time, orf1ab, ORF10, and ORF3a proteins could coordinate attack the heme on the 1-beta chain of hemoglobin to dissociate the iron to form the porphyrin.The attack will cause less and less hemoglobin that can carry oxygen and carbon dioxide. The lung cells have extremely intense poisoning and inflammatory due to the inability to exchange carbon dioxide and oxygen frequently, which eventually results in ground-glass-like lung images.The mechanism also interfered with the normal heme anabolic pathway of the human body, is expected to result in human disease. According to the validation analysis of these finds, chloroquine could prevent orf1ab, ORF3a, and ORF10 to attack the heme to form the porphyrin, and inhibit the binding of ORF8 and surface glycoproteins to porphyrins to a certain extent, effectively relieve the symptoms of respiratory distress. Favipiravir could inhibit the envelope protein and ORF7a protein bind to porphyrin, prevent the virus from entering host cells, and catching free porphyrins. Because the novel coronavirus is dependent on porphyrins, it may originate from an ancient virus. Therefore, this research is of high value to contemporary biological experiments, disease prevention, and clinical treatment.
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Porphyrin
Porphyrins are the conjugate acids of ligands that bind metals to form complexes. The metal ion usually has a charge of 2+ or 3+. A schematic equation for these syntheses is shown:
- H2porphyrin + [MLn]2+ → M(porphyrinate)Ln−4 + 4 L + 2 H+, where M = metal ion and L = a ligand
A porphyrin without a metal-ion in its cavity is a free base. Some iron-containing porphyrins are called hemes. Heme-containing proteins, or hemoproteins, are found extensively in nature. Hemoglobin and myoglobin are two O2-binding proteins that contain iron porphyrins. Various cytochromes are also hemoproteins.
COVID-19: Attacks the 1-Beta Chain of Hemoglobin and Captures the Porphyrin to Inhibit Human Heme Metabolism
The results showed the ORF8 and surface glycoprotein could bind to the porphyrin, respectively.
At the same time, orf1ab, ORF10, and ORF3a proteins could coordinate attack the heme on the 1-beta chain of hemoglobin to dissociate the iron to form the porphyrin.
The attack will cause less and less hemoglobin that can carry oxygen and carbon dioxide. The lung cells have extremely intense poisoning and inflammatory due to the inability to exchange carbon dioxide and oxygen frequently, which eventually results in ground-glass-like lung images. The mechanism also interfered with the normal heme anabolic pathway of the human body, is expected to result in human disease.
According to the validation analysis of these finds, chloroquine could prevent orf1ab, ORF3a, and ORF10 to attack the heme to form the porphyrin, and inhibit the binding of ORF8 and surface glycoproteins to porphyrins to a certain extent, effectively relieve the symptoms of respiratory distress.
At the same time, orf1ab, ORF10, and ORF3a proteins could coordinate attack the heme on the 1-beta chain of hemoglobin to dissociate the iron to form the porphyrin.
The attack will cause less and less hemoglobin that can carry oxygen and carbon dioxide. The lung cells have extremely intense poisoning and inflammatory due to the inability to exchange carbon dioxide and oxygen frequently, which eventually results in ground-glass-like lung images. The mechanism also interfered with the normal heme anabolic pathway of the human body, is expected to result in human disease.
According to the validation analysis of these finds, chloroquine could prevent orf1ab, ORF3a, and ORF10 to attack the heme to form the porphyrin, and inhibit the binding of ORF8 and surface glycoproteins to porphyrins to a certain extent, effectively relieve the symptoms of respiratory distress.
Attack of oxidized hemoglobin by viral proteins will lead to less and less hemoglobin that can carry oxygen. The invasion of viral proteins on deoxidized hemoglobin will cause less and less hemoglobin that can carry carbon dioxide and blood sugar. People with diabetes can have unstable blood sugar.
The patient is aggravated by carbon dioxide poisoning. The lung cells have extremely intense inflammation due to the inability to exchange carbon dioxide and oxygen frequently, which eventually results in ground-glass-like lung images.
Patients with respiratory distress will be made worse.
The patient is aggravated by carbon dioxide poisoning. The lung cells have extremely intense inflammation due to the inability to exchange carbon dioxide and oxygen frequently, which eventually results in ground-glass-like lung images.
Patients with respiratory distress will be made worse.
CT Scans Show What COVID-19 Can Do To Your Lungs
https://iflscience.com/health-and-medicine/ct-scans-show-what-covid19-can-do-to-your-lungs/
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Cooperativity
When oxygen binds to the iron complex, it causes the iron atom to move back toward the center of the plane of the porphyrin ring (see moving diagram). At the same time, the imidazole side-chain of the histidine residue interacting at the other pole of the iron is pulled toward the porphyrin ring. This interaction forces the plane of the ring sideways toward the outside of the tetramer, and also induces a strain in the protein helix containing the histidine as it moves nearer to the iron atom. This strain is transmitted to the remaining three monomers in the tetramer, where it induces a similar conformational change in the other heme sites such that binding of oxygen to these sites becomes easier.
As oxygen binds to one monomer of hemoglobin, the tetramer's conformation shifts from the T (tense) state to the R (relaxed) state. This shift promotes the binding of oxygen to the remaining three monomer's heme groups, thus saturating the hemoglobin molecule with oxygen.[63]
In the tetrameric form of normal adult hemoglobin, the binding of oxygen is, thus, a cooperative process. The binding affinity of hemoglobin for oxygen is increased by the oxygen saturation of the molecule, with the first molecules of oxygen bound influencing the shape of the binding sites for the next ones, in a way favorable for binding. This positive cooperative binding is achieved through steric conformational changes of the hemoglobin protein complex as discussed above; i.e., when one subunit protein in hemoglobin becomes oxygenated, a conformational or structural change in the whole complex is initiated, causing the other subunits to gain an increased affinity for oxygen. As a consequence, the oxygen binding curve of hemoglobin is sigmoidal, or S-shaped, as opposed to the normal hyperbolic curve associated with noncooperative binding.
A schematic visual model of oxygen-binding process, showing all four monomers and hemes, and protein chains only as diagrammatic coils, to facilitate visualization into the molecule. Oxygen is not shown in this model, but, for each of the iron atoms, it binds to the iron (red sphere) in the flat heme. For example, in the upper-left of the four hemes shown, oxygen binds at the left of the iron atom shown in the upper-left of diagram. This causes the iron atom to move backward into the heme that holds it (the iron moves upward as it binds oxygen, in this illustration), tugging the histidine residue (modeled as a red pentagon on the right of the iron) closer, as it does. This, in turn, pulls on the protein chain holding the histidine.
https://en.wikipedia.org/wiki/Hemoglobin
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Now go back and read that Medium link and it makes a bit more sense (or reading the Medium piece and THEN reading the PDF makes more sense – depends on your background in biology, biochemistry, et al. SJWs via gender studies won’t understand a bit of it).
The rest of the PDF gets into a lot of of detail, so let me put this forward. I emailed my RN sister-in-law who has been at Mass General in Boston for decades. She had been the top nurse on the day surgery floors but just got reassigned to the COVID-19 floors (along with my niece who is also a (relatively new) nurse. I sent her Steve’s piece in trying to get the details verified – it looked good to me but my biology, I will admit, is a bit rusty. She’s trying to find folks to run that past to see if it is a kook idea or not.
However, this PDF info really seems legit and fits in with what I remember.
If chloroquine and hydroxychloroquine can do what both sources say, it’s a new ball game and a game changer.
However, consider this “developing”.
Sitenote: I sit here and am AMAZED to see how fast we can pick this new disease apart – an acceleration of biotech. In addition, we ALL should be in awe of the engineers, researchers, and docs who are “warping” old techniques and technology and adapting them so quickly. And a pat on the back all around on all the ordinary people coming up with rather out-of-the-box and innovative ways to meet needs that many thought were “un-meetable” in the short term.
Note: my sister in law sent this video. It is LONG – an hour. But if you have any desire to get detailed info on the biological / physiological background on how COVID-19 works and affects the body, you REALLY WANT to watch it:
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