Haitchpeasauce | 12 points
CD147-spike protein is a novel route for SARS-CoV-2 infection to host cells (Nature, China 04 December 2020) - Not directly about Ivermectin, but relevantSo we may need ACE2 + TMPRSS2 + CD147 inhibitors together. Ivermectin, nitaxozanide and Ambroxol.
[-] Haitchpeasauce | 2 points
This is definitely something we need exploring. No single drug does it all, the virus has many tricks.
[-] who_that_guy227 | 2 points
Don't tell them or ivermectin will get more expansive.
[-] Haitchpeasauce | 1 points
Another study finding SARS-CoV-2 is interacting with the CD147 receptor.
[-] Haitchpeasauce | 3 points | Dec 15 2020 13:09:36
I came across the paper from this excellent Whiteboard Doctor video. It is not a study of Ivermectin, but the research was so thorough and the findings so significant and relevant to Ivermectin that I think it deserves a post. Mods please feel free to decide.
We know now that SARS-CoV-2 has binding affinity to a number of receptors: ACE2 as the strongest target, TMPRSS2 to cleave the S-protein and facilitate entry, and NRP1 (which I am yet to explore). This paper demonstrates that the SARS-CoV-2 spike protein does indeed bind with CD147 transmembrane glycoprotein.
We are familiar with CD147 from David Scheim's paper which theorises that SARS-CoV-2 is binding to CD147 which is present in abundance on red blood cells and platelets, causing them to form clumps and to stick to vascular epithelial cells which also express CD147, causing thrombi. SARS-CoV-2 lacks hemagglutinin erastase which dissolves the clumps. The result is vascular occlusion (clotting) leading to reduced O2 saturation, inflammation and leaky vessels.
As discussed in Scheim's paper, it is theorised that Ivermectin inhibits the binding of the S protein to CD147, preventing these clots from forming. This theory has not been explored much.
CD147 is also expressed on many other cells, including lymphocytes and monocytes. SARS-CoV-2 has been observed in various studies to be present inside these immune cells. These cells do not become replication hosts, but reportedly exhibit unusual cytokine behaviour and become long-lived where normally these cells quickly die. It is possible that these long lived leukocytes are contributors to the cytokine dysregulation and immune cell imbalances.
Ivermectin inhibits the NF-κB signalling pathway, modulating cytokine production.
In summary, CD147 potentially plays a significant role in the observed clotting, immune dysregulation and chronic symptoms.
Abstract
In face of the everlasting battle toward COVID-19 and the rapid evolution of SARS-CoV-2, no specific and effective drugs for treating this disease have been reported until today. Angiotensin-converting enzyme 2 (ACE2), a receptor of SARS-CoV-2, mediates the virus infection by binding to spike protein. Although ACE2 is expressed in the lung, kidney, and intestine, its expressing levels are rather low, especially in the lung. Considering the great infectivity of COVID-19, we speculate that SARS-CoV-2 may depend on other routes to facilitate its infection. Here, we first discover an interaction between host cell receptor CD147 and SARS-CoV-2 spike protein. The loss of CD147 or blocking CD147 in Vero E6 and BEAS-2B cell lines by anti-CD147 antibody, Meplazumab, inhibits SARS-CoV-2 amplification. Expression of human CD147 allows virus entry into non-susceptible BHK-21 cells, which can be neutralized by CD147 extracellular fragment. Viral loads are detectable in the lungs of human CD147 (hCD147) mice infected with SARS-CoV-2, but not in those of virus-infected wild type mice. Interestingly, virions are observed in lymphocytes of lung tissue from a COVID-19 patient. Human T cells with a property of ACE2 natural deficiency can be infected with SARS-CoV-2 pseudovirus in a dose-dependent manner, which is specifically inhibited by Meplazumab. Furthermore, CD147 mediates virus entering host cells by endocytosis. Together, our study reveals a novel virus entry route, CD147-spike protein, which provides an important target for developing specific and effective drug against COVID-19.
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[-] blueheelercd | 1 points | Dec 18 2020 07:23:50
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3636557. Sent to me by FLCCC. Ivermectin
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[-] Haitchpeasauce | 2 points | Dec 18 2020 08:00:04
Yes that's the one linked above. I want to clarify that to date I have not seen papers by other researches further investigating this theory, so in my mind the clumping theory is not yet validated.
For me the big take away is that SARS-CoV-2 is potentially invading leukocytes via CD147 from where the virus can dysregulate their cytokine signalling pathways.
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[-] blueheelercd | 1 points | Dec 18 2020 16:46:35
Yes, I hope so, especially because we still need effective treatments until there is herd immunity, if and when. Also how long will the vaccine be effective? As far as I know the vaccine manufacturers have not informed us as to weather it is possible to shed live virus between the doses, infecting others? My last concern is future Covid pandemics and treatment. I hope scientists will keep the focus on treatments too, as all the eggs seem to have gone into the vaccine basket.
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