nCoV-2019 proximal docking receptors
Primary overview of current known proximal docking receptors for nCoV-2019 as of July, 2020:
CD143: Much has been made about hACE2 (CD143) but little to nothing has ever been mentioned in the scientific community about the overall disruption of the Renin–angiotensin system (RAS), given that this is partially regulating blood pressure and RAS issues lead to hypertension and heart attacks it should have been obvious to doctors from the start to put patients on anticoagulants as opposed to ventilators. Calling this a respiratory disease is like saying Whole Foods is a Cheese Market. While partially true, it is only a small part of the story. This is something I noted back in February and was requesting hospitals use alternative methods as ventilators would cause harm.
CD147: There have been barely any papers into the impacts of the hijacked CD147 (Basigin) system. This is also likely to be causing clotting issues and is likely why anti-malaria drugs have been working on certain patients. It is also likely that when CD147 is hijacked it has the potential to develop tumors (likely benign) or plasmodium invasions.
BiP: There are a total of 4 videos on YouTube that even mentioned that GRP78 has been hijacked. More attention should be given to this issue as that this is a master chaperone of unfolded proteins, me thinks protein rerouting is occurring and potentially hijacked cleaving during healthy protein folding!!! This hijacking likely causes communication issues with the endoplasmic reticulum.
ADAM17: Zero mentions on YouTube. ADAM metallopeptidase domain 17 (TACE – tumor necrosis factor-α-converting enzyme). I have not looked into this but this could be a cleavage hijack happening and this could be used by GRP78.
Furin: The Furin site was discovered way back in February and barely anyone has talked about this in research papers. If anything, this is of more significance than the ACE2 docking since the cleavage is changing the NT of the RBD in such an incredible way. Even when the initial genome was released and we began researching the virus, no one was away of this unique cleavage insertion and that Furin was playing a major role in the cleavage. For me, the fact that PACE is hijacked is the scariest part of the virus. Papers have only discussed how the Furin site impacts virulence to ACE2 but I am more curious about the impact it is having on GRP78 and CD4!
CD4: This hijack is slowly making news but for the wrong reason and many people are under the impression that nCoV contains the HIV virus, which is pure misinformation. It is strongly suggested but not peer-reviewed that the virus contains some HIV homology and residues that may be key factors for CD4 docking. When the virus does take this route, patients could potentially test false-positive for HIV. More importantly, since the immune system is being compromised in a similar fashion to how HIV would work, it is my understanding that patients could develop “HIV-like symptoms“. Obviously not suggesting that a patient could develop HIV. Another scientist had mentioned that both DC-SIGN (CD209) and CLEC4M (CD299) were compromised via CD4.
** A quick note about the nCoV-2019 RBD: The S1/S2 protease cleavage site (330-521) contains an RxxR (RRxR) motif. There are also KxxK motifs or KKxK. Not to be confused with the KKxx motif in the ER! A number of these KKxK motifs exist in the ORF1ab and E proteins as well as a HKNNKS insertion in the RBD section of the Spike protein.
This is also gaining more credibility as new information comes out – https://www.biorxiv.org/content/10.1101/2020.01.30.927871v1
I strongly recommend reviewing the following videos:
nCoV-2019 pathways – https://www.youtube.com/watch?v=LfeF9RzP8DY&t=159s
nCoV-2019 virology – https://www.youtube.com/watch?v=80nAWM-mt4k&t=485s
(this is in Mandarin, the charts are helpful, but I can translate for anyone)
This was moved from the low-visibility ‘Controverial Topics’ subforum, and for some reason my reply (and that of at least one other poster) was deleted in the process, but Dr. Mayer was able to retrieve my post and reply by PM, which I’ll reproduce below with my reply to his reply:
I was able to somehow locate your reply
>I had also been thinking about this, that it apparently requires both S protein priming by serine protease TMPRSS2 and a furin cleaving to even be able to enter cells via ACE2, which seems too complex to happen naturally.
Agreed and the fact that the furin cleavage site contains an RxRR motif from the START is pretty ridiculous, we have never seen this happen before in world history. Evolution does not work like this.
And when has a virus ever had this apparent vast range of different effects? Surely much of the early deaths were due to ignorance and terrible treatments, and newer deaths remain greatly influenced by immunoincompetence due to nutrient deficiencies (chiefly vitamin D) and vaccine adjuvants like aluminum injections (from e.g. flu shots) and other accumulated toxic substances, explaining the degree of asymptomatics, but the virus still seems to be able to bind to multiple targets in addition to ACE2 on any organ/tissue…
>ACE2 also seems to be have a low expression in lungs compared to other organs. There’s gotta be other routes. Why are you still calling it nCoV-2019? Is this info 4+ months old?
I refuse to call this SARS as this is clearly not a respiratory attacking virus. This virus is primarily hijacking the RAS system and creating coagulation issues which are mainly leading to hypoxic conditions. Calling this SARS is entirely misleading and absolutely an attribute as to why doctors around the world forced patients onto ventilators. I also refuse to call this virus/infection COVID as a virus is not a disease but can cause a disease. Just as people incorrectly interchange HIV and AIDS, the same is true here. At GISAID we are calling this hCoV-2019. I am happy to use that nomenclature here on the board as well.
Ah, interesting point. It was named SARS-CoV-2 on 11 Feb 2020 by the International Virus Classification Commission (ICTV), presumably simply because it was seen to be similar in effects to SARS-CoV and MERS (SARS-CoV-1.5 you could say), the previous two coronaviruses infecting humans since the 4 much older ones (two of which contribute ~15% to the common cold), and shares significant sequence homology (I think ~79%). My perception is that the WHO and the Gates-centered global health mafia — who have been funding gain-of-function research (years prior to the outbreak), pandemic preparedness (including censorship efforts, weeks prior to the outbreak), contact tracing efforts (3-6 months prior to the outbreak), etc — wanted to call it something else that would not link it directly to SARS-CoV[-1] which also came out of China in similar circumstances, and which is associated with failed vaccine efforts.
But doesn’t it also to a certain degree present as a severe acute respiratory syndrome, and sometimes ARDS, leaving scars in lung tissue? Just not always; might it depend on the ACE2-expressing organs it reaches? Though I’ve read accounts of people with chest pain and shortness of breath for weeks, thinking their lungs must be totally trashed, but it turns out their lungs are fine.
I would think that if it’s more mediated by RAS dysfunction itself, via antagonizing ACE2 (which converts active angiotensin II to inactive angiotensin I), rather than ACE2 just being a tunnel/bridge for cell entry, that we would see the hyperinflammation coupled with hypotension (although maybe just localized to the lungs?). Also, nicotine (due to nicotinic acetylcholine receptor agonism or some other mechanism) and estrogen seem to cause ACE2 downregulation, making smokers and women less vulnerable to the virus rather than more. I’m far from an expert on RAS though, I’m sure I’m missing some mechanisms… What do you think is the main mechanism(s) that leads to coagulation issues which then leads to hypoxia?
BTW, what are your thoughts on HIV/AIDS? Is the Duesberg camp correct?
>I had never even heard of BiP/GRP78 or ADAM17. Is BiP hijacking related to the idea of heme groups in hemoglobin losing their oxygen binding ability?
It is not. BiP (GRP78) interference would play a role in the destabilization of the endoplasmic reticulum. More importantly, this is the master chaperone for unfolded protein response. So the virus could theoretically adapt BiP to fold healthy proteins in a slightly different manner, causing nucleic acid changes and destabilizing various proteins in cells throughout the body. Above a threshold of accumulated unfolded proteins, GRP78 releases ATF6, PERK, and IRE1, leading to their activation. Inhibition of protein synthesis and enhancement of the refolding is the end result of the enzymes’ activation. Potential overexpression of GRP78 from the virus is also initiated upon cell stress, which increases the chance for GRP78 to escape ER retention and translocate to the cell membrane. Once translocated to the cell membrane, GRP78 is susceptible to virus recognition by its substrate-binding domain (SBD), and it can mediate the virus entry in the cell. We have confirmation of BiP hijacking during the MERS outbreak and that led to cellular destabilization in patients when this route was attacked.
Interesting, so this viral entry mechanism already existed in the previous human coronavirus outbreak. What are your thoughts on SARS1 and MERS — are they also lab chimeras with gains-of-function? Some Russian and Chinese researchers did suggest SARS1 was lab-made.
>Are you an anonymous Jewish doctor/virologist fluent in Mandarin, and that’s all you want to reveal?
I am German and lived in Hong Kong for a number of years in my earlier years. I am fortunate to be able to speak several languages. The link in Mandarin that I had provided in a post contains a wealth of information and the Doctor in the video was at least 4 months ahead of nearly all science at the time.
Danke mein Herr. 😉
Q: Ah, interesting point. It was named SARS-CoV-2 on 11 Feb 2020 by the International Virus Classification Commission (ICTV), presumably simply because it was seen to be similar in effects to SARS-CoV and MERS (SARS-CoV-1.5 you could say), the previous two coronaviruses infecting humans since the 4 much older ones (two of which contribute ~15% to the common cold), and shares significant sequence homology (I think ~79%). My perception is that the WHO and the Gates-centered global health mafia — who have been funding gain-of-function research (years prior to the outbreak), pandemic preparedness (including censorship efforts, weeks prior to the outbreak), contact tracing efforts (3-6 months prior to the outbreak), etc — wanted to call it something else that would not link it directly to SARS-CoV[-1] which also came out of China in similar circumstances, and which is associated with failed vaccine efforts.
A: We humans always need to compare things in order to attempt to understand a new experience. Dr. Ai Wen in Wuhan was the first to suggest this was a SARS-like virus causing pneumonia in patients. Before pathology and virology research had been conducted on the virus it was already dubbed SARS2 within China. This was a rush to judgment and many people died because of this. To the untrained eye, this virus presents very similar to SARS and can produce ARDS similar to SARS-CoV. Please also recall that very few doctors and scientists outside of Asia have any experience dealing with SARS in hospitals or in research labs. This really appears to be a clinical case of “treat this respiratory virus as a respiratory virus because it is called a respiratory virus”. There is no underlying conspiracy there.
Q: But doesn’t it also to a certain degree present as a severe acute respiratory syndrome, and sometimes ARDS, leaving scars in lung tissue? Just not always; might it depend on the ACE2-expressing organs it reaches? Though I’ve read accounts of people with chest pain and shortness of breath for weeks, thinking their lungs must be totally trashed, but it turns out their lungs are fine.
A: Yes, this is the pathology issue with this virus, it arrived as a swiss-army knife with keys to no less than 6 different receptors. The symptoms, infection, and selected receptors would greatly vary between patients due to a number of factors including comorbidities. We did not see this with SARS-CoV as it had (poor) access to hACE2 and was predominately impacting respiratory systems of patients. There is too much focus on hACE2 impact when CD4, Basigin, GRP78 (among others) are being used to impact organs, protein folding, cellular destabilization, and deterioration. That being said, patients presenting with ARDS would almost always be due to the hACE2 route attacking the alveoli. Although I do not know the statistics, it appears that ARDS is only presenting in a comparatively small number of patients, whereas with SARS-CoV it was a much higher presentation. In the situations where patients are complaining of lung issues but there is “no problem”, this is a hypoxia issue due to RAS regulation causing coagulation issues as well as (sometimes) reducing the production of hemoglobin.
Q: I would think that if it’s more mediated by RAS dysfunction itself, via antagonizing ACE2 (which converts active angiotensin II to inactive angiotensin I), rather than ACE2 just being a tunnel/bridge for cell entry, that we would see the hyperinflammation coupled with hypotension (although maybe just localized to the lungs?).
A: This is absolutely correct. In cases with small viral load, there would be less disruption of the hACE2 system and therefore little to no impact on the RAS system. I believe doctors are seeing hyper inflammation but are repeatedly overlooking it. Why? If I tell a Doctor this is a respiratory illness that will cause SARS but in reality, there is a clotting issue in your foot causing hypertension, do you actually think they would discover the problem? In fact, only a few Doctors did, and most were disciplined for even questioning the practices of attendings. Rather than diagnose the patients, the Doctors are being told this is a respiratory syndrome and therefore the patient needs to be ventilated, meanwhile the foot is ignored throughout the entire hospital stay. For clarification, the reference to a foot is simply an analogy.
Q: Also, nicotine (due to nicotinic acetylcholine receptor agonism or some other mechanism) and estrogen seem to cause ACE2 downregulation, making smokers and women less vulnerable to the virus rather than more. I’m far from an expert on RAS though, I’m sure I’m missing some mechanisms… What do you think is the main mechanism(s) that leads to coagulation issues which then leads to hypoxia?
A: You should read up on ACE inhibitors and why patients prior to “COVID” required them. Patients with high blood pressure, susceptibility to clotting, and hypertension are at greater risk to the ACE system (and RAS to a degree) turning on them. There are situations where the system breaks and ACE begins attacking the body causing either hypertension, coagulation, clotting, heart attacks. These attacks are almost triggered by underlying medical conditions. Qualified patients take ACE inhibitors to reduce the “number” of functional ACE receptors throughout their body. How many ACE receptors we have varies person to person. On top of that, regardless of your count, not all will function correctly. ACE regulation, attacks, or risks greatly vary. Once “COVID” began, Doctors advised patients that had already been taking ACE inhibitors to continue their medication as normal. Smokers have already compromised many aspects of their internal systems, including ACE functionality. Many smokers already have blood pressure issues. It is highly probable that many of these patients would have reduced ACE levels, thus fewer options for this route of attack. Although this potentially would make the patients less vulnerable to ACE hijacking, we would expect to see the declining quality of life due to their immune system being compromised. If the virus was primarily presenting via ACE in a patient that had a pretty bad ACE regulation system, the virus would look for a better route, perhaps CD4. Virtually no one is doing research on CD4 immune impacts at this point. This is, in part, why we are seeing “recovered patients” with horrible ailments. Clinically a “recovered” patient is someone that did not die from “COVID”.
Q: what are your thoughts on HIV/AIDS? Is the Duesberg camp correct?
A: I do not have much background on HIV as I am in the betacoronavirus group. I do not agree with Duesbergs’ assertions. There is a REKR polybasic cleavage site in the GP160 protein of HIV. The cleavage site is very similar to H5N1 (RKKR) and H5 influenza (REKR), the presence of this motif tells us that the virus will likely have very good expression in the host cell. More importantly, the GP160 receptor “fit” to CD4 is incredible. Just for clarification to everyone that HIV will absolutely compromise the immune system and leave the host with a cascade of medical issues. As for AIDS itself, I cannot say much as that is not my field. I work in the virus part, not the disease part. It seems a pretty logical conclusion that a heavy viral load of HIV could lead to AIDS.
Thanks for the fun reply 🙂
Bump. More people should read this thread.