Well done, thank you. As an aside on Stephen Buhner's plant based protocol, we have tailored the long covid protocol for several people with really good results and no side effects (some of the mentioned pHarma have nephro toxicity and other side effects). As well we have used the Covid treatment protocol for several who had active infection, again with excellent results, including one who was two weeks into his symptoms.
Thanks for the response! I had a bit of an allergy fit and so the end of this post was kind of put together haphazardly. I meant to include a remark that you have treated people with this regimen. Would you mind if I included this correction?
Yes you are welcome to do so. I have become an herbalist on my retirement and my wife is am MD who always offered herbs to get patients. The vast majority of botanicals have a phenomenal safety profile.
Some notes on the stabilization part, with the caveat that my research here is still VERY half-baked. Essentially my understanding matches the overall gist but is even a bit worse than how you have phrased it.
The Proline subs were at the bottom (C-term) of HR1, per https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7829931/ - Also it was KV originally, so not an intuitively radical substitution compared to taking out some hydrophobes in the middle of HR1 and I don't get the impression that any real-life testing confirmed the effect.
"However, the two amino acid replacements (K986P, V987P), shown in Figure 5, stabilize the resulting spike protein in the prefusion state and contribute to vaccine efficiency. The mutant SARS-2-S spike protein with these proline replacements is referred to as S-2P [85,86], which is encoded in the mRNA vaccine from both Pfizer/BioNTech (BNT162b2) and Moderna (mRNA-1273)."
Placed here, the "stability" conferred is that HR1 can't fire upward into nearby membranes, facilitating fusion. But all the conformational changes before then are still possible. That includes premature (pre-binding) cleavage / break-off of the S1 unit., as well as ACE-2 adjacent (during binding) cleavage, though the latter might not be as bad as the former once you have locked HR1 in place.
Essentially it is like they locked the "Jack" of the jack in the box in place, but the lid can still fall off and fly around in the blood and do whatever (besides obviously being exposed to the blood anyway if it is expressed on endothelial membranes).
Ah thank you! I really need to look further into this research! The most important aspect is that the proline residues force a permanent "kink" into the helix. It's like locking a finger's joint so that it only points sideways and can't move up and down. I'll add that correction to my post.
Yes, that is pretty much my impression. But it still seems like a weird approach, kind of like a red herring. "Oh, look, we can stop the VERY last stage before fusion" does not equal "stabilized." And then "Oh, look, link to an old tiny MERS study." It all smells funny.
I usually have trouble visualizing protein structures with 3d rendered models unless there are fluid dynamics involved so it usually gets lost on me, but yes it seems rather strange that the focus has bee solely on its fusion states when its ability to bind to other receptors may not heavily depend on these activities. It's weird seeing people take this slight modification as an indication that all is well.
Interesting. I've been visualizing the spike protein (and Class I fusion motif in general) in the context of surrounding liquid, despite my jack-in-the-box reference. I think of the HRs like floaty pool tubes. But I'm still sorting through all the literature on how the HRs really behave during fusion, where the "fusion peptide" goes, etc.
I probably should have worded it differently. I meant fluid in the sense that I need to see it in motion which you usually don't get in papers. Usually someone has to come up with some sort of animation to show that but then you have to question if the animations are far too simplified that they don't capture the actual nature of what's going on. Hope that clarifies it a bit.
Taken as individual articles,or, taken as an organic whole, a series of continuous crucial explanations, the intent to help mankind is magnificent and munificent. Moreover, it is scientifically verifiable as well as crucially available at just the proper time.Sir, I respectfully submit, that you are and have been, a benefactor of mankind, an example to be emulated and repeated , if it please G-d.
Thank you! I never start writing these series with the intent of making them multiple posts. Originally I would wait until I had all of it written out, in which case that usually results in sloppily chopping up a 30-40 post into smaller pieces. Now it's more about what topics I tend to include within these posts that dictate how long they tend to be, and it usually means I work and post segments as I move along. It's a bit more of a risky move since the Fluvoxamine post meant I had to cover mechanisms of action that I didn't cover previously which resulted in a lot more space being taken up than I would have wanted just to provide more context.
I hope people find this information fruitful. Even with a lot of the amazing discourse happening on Substack I'm a bit dismayed at the amount of scientists and researchers on here who are not covering much science and research. Maybe it's me being within my own bubble I would hope that more people understand that there is a huge yearning to learn and expand people's minds!
Also, even as someone who is not religious, do not feel the need to censor any words. It certainly doesn't offend me and it shouldn't offend others. In fact, I would hope that people don't come in here believing that their thoughts or beliefs should be censored.
Please note that a few corrections and additional information was provided to the newsletter. Please look out for that information.
Well done, thank you. As an aside on Stephen Buhner's plant based protocol, we have tailored the long covid protocol for several people with really good results and no side effects (some of the mentioned pHarma have nephro toxicity and other side effects). As well we have used the Covid treatment protocol for several who had active infection, again with excellent results, including one who was two weeks into his symptoms.
Aloha y'all
Thanks for the response! I had a bit of an allergy fit and so the end of this post was kind of put together haphazardly. I meant to include a remark that you have treated people with this regimen. Would you mind if I included this correction?
Yes you are welcome to do so. I have become an herbalist on my retirement and my wife is am MD who always offered herbs to get patients. The vast majority of botanicals have a phenomenal safety profile.
Aloha
Interesting! I'll add that tidbit as well!
Some notes on the stabilization part, with the caveat that my research here is still VERY half-baked. Essentially my understanding matches the overall gist but is even a bit worse than how you have phrased it.
The Proline subs were at the bottom (C-term) of HR1, per https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7829931/ - Also it was KV originally, so not an intuitively radical substitution compared to taking out some hydrophobes in the middle of HR1 and I don't get the impression that any real-life testing confirmed the effect.
"However, the two amino acid replacements (K986P, V987P), shown in Figure 5, stabilize the resulting spike protein in the prefusion state and contribute to vaccine efficiency. The mutant SARS-2-S spike protein with these proline replacements is referred to as S-2P [85,86], which is encoded in the mRNA vaccine from both Pfizer/BioNTech (BNT162b2) and Moderna (mRNA-1273)."
Placed here, the "stability" conferred is that HR1 can't fire upward into nearby membranes, facilitating fusion. But all the conformational changes before then are still possible. That includes premature (pre-binding) cleavage / break-off of the S1 unit., as well as ACE-2 adjacent (during binding) cleavage, though the latter might not be as bad as the former once you have locked HR1 in place.
Essentially it is like they locked the "Jack" of the jack in the box in place, but the lid can still fall off and fly around in the blood and do whatever (besides obviously being exposed to the blood anyway if it is expressed on endothelial membranes).
Ah thank you! I really need to look further into this research! The most important aspect is that the proline residues force a permanent "kink" into the helix. It's like locking a finger's joint so that it only points sideways and can't move up and down. I'll add that correction to my post.
Yes, that is pretty much my impression. But it still seems like a weird approach, kind of like a red herring. "Oh, look, we can stop the VERY last stage before fusion" does not equal "stabilized." And then "Oh, look, link to an old tiny MERS study." It all smells funny.
I usually have trouble visualizing protein structures with 3d rendered models unless there are fluid dynamics involved so it usually gets lost on me, but yes it seems rather strange that the focus has bee solely on its fusion states when its ability to bind to other receptors may not heavily depend on these activities. It's weird seeing people take this slight modification as an indication that all is well.
Interesting. I've been visualizing the spike protein (and Class I fusion motif in general) in the context of surrounding liquid, despite my jack-in-the-box reference. I think of the HRs like floaty pool tubes. But I'm still sorting through all the literature on how the HRs really behave during fusion, where the "fusion peptide" goes, etc.
I probably should have worded it differently. I meant fluid in the sense that I need to see it in motion which you usually don't get in papers. Usually someone has to come up with some sort of animation to show that but then you have to question if the animations are far too simplified that they don't capture the actual nature of what's going on. Hope that clarifies it a bit.
Taken as individual articles,or, taken as an organic whole, a series of continuous crucial explanations, the intent to help mankind is magnificent and munificent. Moreover, it is scientifically verifiable as well as crucially available at just the proper time.Sir, I respectfully submit, that you are and have been, a benefactor of mankind, an example to be emulated and repeated , if it please G-d.
Thank you! I never start writing these series with the intent of making them multiple posts. Originally I would wait until I had all of it written out, in which case that usually results in sloppily chopping up a 30-40 post into smaller pieces. Now it's more about what topics I tend to include within these posts that dictate how long they tend to be, and it usually means I work and post segments as I move along. It's a bit more of a risky move since the Fluvoxamine post meant I had to cover mechanisms of action that I didn't cover previously which resulted in a lot more space being taken up than I would have wanted just to provide more context.
I hope people find this information fruitful. Even with a lot of the amazing discourse happening on Substack I'm a bit dismayed at the amount of scientists and researchers on here who are not covering much science and research. Maybe it's me being within my own bubble I would hope that more people understand that there is a huge yearning to learn and expand people's minds!
Also, even as someone who is not religious, do not feel the need to censor any words. It certainly doesn't offend me and it shouldn't offend others. In fact, I would hope that people don't come in here believing that their thoughts or beliefs should be censored.
Anyways, have a great day Morton!