I watched Dr. Chetty's original video which caused his legal problems and felt relieved that somebody was voicing my own suspicions. Most people opposed to the COVID policies blame them on greedy pharmaceutical companies and their corrupting influence on regulators, journals, universities, etc. While that was clearly a factor, I suspect there were other goals and more powerful actors at work. Probably the truth is like peeling the layers of an onion where naive doctors think the goal is saving lives and pharmaceutical executives think the goal is profit, and some sort of international organization might think the goal is saving the Earth from global warming or saving the retirement programs. Also some things may not have gone the way people hoped, so that makes discerning the goals even more difficult.
Regardless of the difficulty of discerning all the actors and their goals, it is important. As you said in the cyanide example, whoever did it will try again.
It's a shame that Dr. Chetty is having these legal problems. I hope he comes through it in good shape somehow.
When Dr. Chetty laid out his treatment protocol, one fundamental thought struck me:
Regardless of the actions initiated by politics or the pharmaceutical industry, ultimately, it is the doctor who has the power to either accept or reject the influences of politics or pharma.
I agree that ultimately doctors are supposed to have a lot of autonomy, but I'm not certan that is true in practice. As I understand it, there are protocols that protect the doctor from liability and disciplinary action, and doctors try to follow those protocols to preserve their careers.
Another factor might be locality. If a doctor has the support of his community and employers then he/she can experiment a little and find what works. I know a local chain of hospitals near my home in the US that serves small towns and has freely experimented with all sorts of COVID treatments with apparent impunity. On the other hand, in this same state of Texas, Dr Peter McCullough and Dr Richard Bartlett have had to defend themselves several times against serious legal challenges. The difference I suspect is publicity. When doctors try to spread the good news outside their supportive locality then they find serious trouble. That's all just my theory. Who knows.
The very reason the pathogen had a low fatality rate overall and relatively higher fatality among the aged and those with preexisting illness, calls for an important role of physicians to intervene with therapeutics with evidence and proven benefits against the illness caused by the pathogen. Not following guidelines and protocols which are not benefiting their patients and recommending a vaccine which failed in its claim of preventing the transmission of the pathogen. Treating those who are vulnerable and sick rather than waiting and promoting a vaccine with no benefit of preventing the transmission is responsible and laudable clinical practice.
Therefore responsible physicians like Dr Chetty with a noble intention of healing their patients without doing no harm should be endorsed and promoted rather than targeted for scrutiny.
On the other hand those who were responsible for contributing to preventable sickness and fatalities by adopting protocols and guidelines with poor outcome stand to be targeted, scrutinised and punished. As a result of lack of professional responsibilities, ethics and conflicts of interests.
More than the virus, the deadlier cause of the pandemic havoc in 2020 and in part 2021 was the collective failure of doctors and clinicians around the world and their ignored first lesson “prevention is better than cure”. The virus gave us 8-10 days to be subdued, the viral phase, like any other respiratory virus, with a set of highly familiar symptoms. Symptoms that have been treated comprehensively and comfortably in other more benign conditions like common cold. If our medicos did not utilise that window and let the population come to grief, it is their fault not that of the virus, even after knowing what the virus was ordained to do next. To be fair, the virus has kept that window open till now and in Omicrons
has even been considerate to the humanity by almost clipping off its deadlier phase. While doctors in many countries, probably inspired by the work of the likes of Dr. Chetty on early treatments and classical medicines, used that window effectively beginning mid 2022, for the officially tutored doctors in the west that window of easy opportunity never existed, pushing the infected into the dark lanes of death. So this pandemic is not about the ways of the virus, but a tale of two sets of doctors, one never willing to remember their first lessons and another recalling that lesson mid course and changing the course of the pandemic in their populations.
The virus must have a pathogenic (active) part and by all evidences it is the spike protein. First and foremost, it is the one that promotes cell entry by binding to the cell surfaces. So, Dr. Chetty is right. Its origin is unknown and may never be known, denying valuable biological knowledge in service of humanity. Besides these, every other point is beyond the point. No matter what the unknown story about this virus is, Dr. Chetty himself showed that it can be tamed safely, comfortably and almost irreversibly, in its early days of infecting an individual with proven old school medicines. That is the cardinal point, picked up by thousands and thousands of doctors in many lesser countries since mid 2021 to banish the virus from their midst. That is why I will be rather charitable to the virus. It didn’t really kill millions. It is the poor clinical understanding from the doctors and medical administrations that did. Additionally in the West, the doctors were hamstrung by their administrators.
I immediately recognized Dr Shankara Chetty as a TRUE covid times HERO. I saw a picture of the parking lot covid treatment tents He had set up to See and Treat People sick with covid with REAL medical treatment for covid which PREVENTED hospitalization and death. I saw a "contrasting" picture of a fully equipped ICU covid treatment room, such as in the west, where so many of the most vulnerable were denied REAL treatment for covid and thus effectively both tortured and also actively euthanized to death by "doctors" and "nurses" directed by a evil system hell bent for power, control and money.
I AM in agreement with Dr Chetty's statements.
In the US "they" have not yet entirely removed the 1st Amendment protecting Our God Given Rights of Freedom of Religion and Speech
Amendment I
Congress shall make no law respecting an establishment of religion, or prohibiting the free exercise thereof; or abridging the freedom of speech, or of the press; or the right of the people peaceably to assemble, and to petition the government for a redress of grievances.
I would base my defense on These God Given Rights The founding Document of the United States of America, The Declaration of Independence states "We hold these truths to be self-evident, that all men are created equal, that they are endowed by their Creator with certain unalienable Rights, that among these are Life, Liberty and the pursuit of Happiness."
My "religion", Path to return to God, of 50 years informs me, that we are now engaged, As Above so below, in a battle for the future of Life On Our Planet Earth and that I Am Required to "noise this abroad".
My "religion", Path to return to God, also informs me as to the specifics, that being that God's Plan leading unto a sustainable Golden Age of Freedom and Opportunity for 9 billion people on Our Planet Earth was preempted by evil in 1998 which, in 2001, opened the door where evil dwells for the beginning of evil's plan to unfold for "their" total control, genetically engineered, depopulated, dystopian "future" for "life" on planet earth.
I see embodied evil, individually acting in pursuit of their own self interests controlling many not in the embodied evil class who do their bidding, in accordance with and in furtherance of the plans of evil at inner levels On Earth evil here and evil there - Wherever large wealth and knowledge is being created evil will be there infesting and infecting the production of that wealth and knowledge and bleeding it off to advance evil's plan for their total control, genetically engineered, dystopian, depopulated future ongoing for the majority of those remaining on "that" planet earth. The plan of evil which now increasing numbers of people across Our Earth see.
With the passage of the "patriot act" in the US after 9 11 2001 effectively all restraints on US bioweapon development were removed and development of mRNA bioweapon countermeasure technology was accelerated. This enabled the US bioweapon "complex" to create a furin cleavage site "insert" for sars-cov which provided the pandemic level of infectiousness (the 2) seen in sars-cov-2. Other bioweapon adaptable countermeasure "sequences" were patented by moderna. This and other bioweapon/bioweapon countermeasure research was "honey trapped", purchased, taken by and transfered to the ccp/pla as the ccp/pla developed it's own bioweapon "innovations".
The "chinese" "communist" party/ "people's" "liberation army bioweapon development complex located a highly virulent sars-cov with a 50% fatality rate when encapsulated within or on bat feces dust when this sars-cov transfected into 6 workers cleaning bat feces from a mine in 2013 killing 3. Of course this sars-cov immediately was sent to ccp/pla bioweapon labs for bioweapon research. In 2017 ccp/pla bioweapon researchers found a pangolin sars-cov spike evolution with exceptional human ACE2 binding affinity by searching through 3533 tissue samples taken from a small group of sick pangolins, identifying on the average, near 10 virus types in each sample to find sars-cov in tissue samples taken from pangolin #7 and in larger number from pangolin #8 and then testing these sars-cov for bioweapon potiential and finding the spike with exceptional human ACE2 binding enabling the "creation" of sars-cov-2 spike. This deduced from an evidenced, including the original then deleted supplementary data, reading of the March 22, 2020 "US" bioweapon/bioweapon countermeasure complex's "hide in plain sight" limited hangout, zoonotic origin / wet market infection epicenter, mis/dis/mal information, propaganda piece "Emergence of SARS-CoV-2 through recombination and strong purifying selection" They carefully tell some truth, always make mention of zoonotic evolution while never actually saying sars-cov-2 was zoonotic (plausible deniability) and never mention lab origin. (just look at where the authors work). This actually spelled out the US "furin cleavage site" bioweapon complex complicit, ccp/pla lab creation of sars-cov-2 - less the numbers of bioweapon "inserts" added to the "spike" of sars-cov-2.
In my defense I would present the evidence showing that the ccp/pla did what it, OF COURSE, would do.
as referenced in the below attached 2 part continued reply I previously posted as comments elsewhere.
The following is my takeaway "on a Carefully Planned Worldwide Bioweapons Attack" I originally posted this comment to a substack page discussing "DEFUSE"
DEFUSE does provides additional evidence of highly developed PREEXISTING bioweapon development work to enhance sars-cov via the addition of a furin cleavage site undertaken prior to 2018 by the US bioweapon / bioweapon and pandemic countermeasure "complex".
"The exact furin cleavage site found in SARS-CoV-2 is found in another protein, a protein called alpha-ENaC found in humans and studied heavily at the same university (UNC) as one of the PI’s of DEFUSE. "
UNC - University of North Carolina at Chapel Hill home of bioweapon baric and the bioweapon baric gain of function gang.
and then DEFUSE, based on prior knowledge writes its proposal showing that "it" has prior knowledge of the location to place the furin cleavage site to weaponize sars-cov thereby "creating" sars-cov-2. "SARS-CoV-2 has its furin cleavage site at exactly the location proposed in these grants."
It is made obvious by the outworking of events that this US developed furin cleave site and specific technology to insert it was "transfered"/taken/stolen and PRIOR to 2018 delivered to the bioweapon / bioweapon and pandemic countermeasure "complex" of the "chinese" communist party/peoples liberation army - ccp/pla.
From the Abstract of "SARS-CoV-2 and the Secret of the Furin Site" "Here we show genomic fingerprints which are specific of Pangolin-CoVs, Bat-SARS-like (CoVZC45, CoVZXC21), bat RatG13 and human SARS-CoV-2 coronaviruses. This, along with phylogenetic analysis, we found that these species have the same evolutionary origin in the bat, including a genetic recombination of S gene between Pangolin-CoV (2017) and RatG13 ancestors." RatG13 "isolated in 2013".
The following from the March 22, 2020 "US" complex "hide in plain sight" limited hangout, zoonotic origin / wet market infection epicenter, mis/dis/mal information, propaganda piece "Emergence of SARS-CoV-2 through recombination and strong purifying selection" (just look at where the authors work)
"We show evidence of strong purifying selection around the receptor binding motif (RBM) in the spike gene and in other genes among bat, pangolin and human coronaviruses, indicating similar strong evolutionary constraints in different host species. We also demonstrate that SARS-CoV-2’s entire RBM was introduced through recombination with coronaviruses from pangolins, possibly a critical step in the evolution of SARS-CoV-2’s ability to infect humans. " "we find significant recombination breakpoints before and after the ACE2 binding site (fig. S2A)," "Specifically, amino acid sequences of the receptor binding motif (RBM) in the C terminal of the S1 subunit are nearly identical to those in two Pan_SL-CoV_GD viruses, with only one amino acid difference (Q498H)—although the RBM region has not been fully sequenced in one of Guangdong pangolin virus (Pan_SL-CoV_GD/P2S)
"Thus, a functional RBM nearly identical to the one in SARS-CoV-2 is naturally present in Pan_SL-CoV_GD viruses. The very distinctive RaTG13 RBM suggests that this virus is unlikely to infect human cells, and that the acquisition of a complete functional RBM (my note; with exceptional human ACE 2 binding ability) by a RaTG13-like CoV through a recombination event with a Pan_SL-CoV_GD-like virus enabled it to use ACE2 for human infection.
note; As this "Research Article" was originally posted to the preprint? server the supplementary data initially contained a spread sheet, subsequently removed, showing on the vertical, line by line, 3533 individual tissue samples taken from a number of sick pangolins. Virus types found in each tissue sample, averaging close to 10 per sample, were listed horizontally - sars-cov was found in sick pangolin #7 and more in sick pangolin #8, more likely the "guilty party" supplying the human ACE 2 binding affinity enhancement identified in sars-cov-2.
"Furthermore, SARS-CoV-2 has a unique furin cleavage site insertion (PRRA) not found in any other CoVs in the Sarbecovirus group (24), although similar motifs are also found in MERS and more divergent bat CoVs (25) (Fig. S3). This PRRA motif makes the S1/S2 cleavage in SARS-CoV-2 much more efficiently than in SARS-CoV and may expand its tropism and/or enhance its transmissibility (23)"
Sars-cov backbone and sars-cov components were on the bioweapon lab shelves of the "chinese" communist party/people's liberation army (ccp/pla) bioweapon / bioweapon and pandemic countermeasure "complex" from 2013 - a sars-cov virus with a 50% fatality rate when transfected in aerosolized bat feces, this cov-2 supplied the "backbone" for sars-cov-2, and from 2017 a pangoplin sars-cov spike component with exceptional binding to human ACE 2.
Recombination and Strong Purifying Selection using these and using "US" furin cleavage site technology that was used to put the "2" into sars-cov, created the "pandemic" level of human to human transmission shown in sars-cov-"2".
Then this ccp/pla bioweapon complex did what it would do - develop a countermeasure vaccine and do human testing while continuing to bio weaponize their sars-cov-2, most particularly the spike*, with various bioweapon toxin inserts and virulence inhibited toxin inserts and continue to do countermeasure vaccine testing on humans. *note; Whole spike which was by that time well "noised abroad" as the choice coronavirus antigen for coding countermeasure agent mRNA.
From events we may see that during this ccp/pla bioweapon/bioweapon countermeasure development process*, in the March 2018 time frame, a virulence inhibited early sars-cov-2 began to spread across China, Asia Pacific and into areas of Chinese contact in Africa developing widespread immunity to sars-cov-2 in the population of those areas which lasted until the immunity breakthrough and increased virulence changes developed into sars-cov-2 seen in the Delta variant. see The Ethical Skeptic "China’s CCP Concealed SARS-CoV-2 Presence in China as Far Back as March 2018 https://theethicalskeptic.com/2021/11/15/chinas-ccp-concealed-sars-cov-2-presence-in-china-as-far-back-as-march-2018/
*note; The modus operandi MO of a bioweapon/bioweapon countermeasure complex is FIRST DEVELOP THE BIOWEAPON
Then a breakdown of virulence inhibition? or a leak or breakthrough infection? or a DELIBERATE DECISION to release a virulent sars-cov-2 as a stealth bioweapon attack on the west with a "pandemic" in china "GO player" cover story and THE DELIBERATE DECISION made by the ccp/pla to use all means necessary to suppress and stop the spread of covid-19 in China and THE DELIBERATE DECISION made by the ccp/pla to use all means necessary, then, to insure that that initial release sars-cov-2 spread to the world and that certain subsequent variants developed and released in "coincidental" conjunction with ccp/pla vaccine testing in foreign countries also spread, quite possibly, initially via bioweapon encapsulation to produce airborne aerosols particles , South African variant, most virulent Gamma P1 in Brazil, or spread across the world and such as Delta and then the case of Omicron. Omicron with the prion creating spike insert toxin reportedly somehow now removed. The prion creating spike insert toxin present in prior variants and replicated by mRNA in the whole spike "vaccine " antigen.
This OMICRON ALLOWED TO SPREAD THROUGH CHINA reportedly doing relatively little damage to the people of China whose immune systems it appears were mostly protected from repeated infections and repeated mRMA injections creating toxic whole spike and doing other damage which made Omicron reportedly much more debilitating and killing in the multiple infection / multiple injection "west". And now, in the west, a omicron with a prion initiating site "insert" reported.
imo - All Total, fact + fact + fact, shows a ccp/pla 2 front , stealth, "unlimited war", "economic war", bioweapon attack on the west. Front #1) sars-cov-2 + "developed" immune escape variants, front #2) ccp/pla tradecraft + fear-inducing showmanship inducing the west to use ccp/pla slow kill bioweapon spike for its countermeasure mRNA and viral vector produced vaccine antigen. Induced with terrible deaths for the most vulnerable elderly and comorbid, people filmed dropping dead, staged?,on China streets. Where else in the world did we see this happening before "vaccines"? Apartment doors welded shut, massive spraying and fogging of the streets and public spaces and the phenomenal construction of hospitals in weeks which were shortly to be closed down.. Quite the show. Quite the FEAR FEAR FEAR producing show inducing the west to use "their" long planned "countermeasure" Mrna to now generate the ccp/pla bio-engineered toxic "slow kill" "spike" for its "vaccine" antigen. Infection, injection, infection, injection, infection, injection death and debilitation in the west, China largely protected with widespread prior immunity until delta with actual lock downs and conventional vaccines. "chinese" Go players vs complicit "western" checkers players.
The facts that the surveillance state ccp/pla "china" 100% knew what was circulating person to person in wuhan and 100% deliberately worked to conceal this while working to keep travel open from wuhan to the world and while they looted the "west's" stocks of N95 shows ccp/pla intent at best to "never let a good crisis go to waste" if the release was somehow not deliberate, while providing "pandemic explanation" cover with 2 "red herring" (ethical skeptic) trails 1) zoonotic origin with wet market outbreak center, to be supported by the west's complicit US bioweapon / bioweapon countermeasure / military / industrial / pharma complex, with full knowledge as to the origin of sars-cov-2, as a cover for their own complicit gain of function (gain of effect) "contribution" the furin cleavage site, the "2", the pandemic level of human to human transmission, in sars-cov-2 and other technology transferred to and taken by the ccp/pla and used by the ccp/pla for the lab recombination "creation" of sars-cov-2. Effective zoonotic "cover" for 3 years yet still being debunked leading to
"red herring" (ethical skeptic) trail 2) "ACCIDENTAL" lab release. How long for this to be debunked?
.... . evil here evil there - evil won round "covid"
a ccp/pla 2 front , stealth, "unlimited war", "economic war", bioweapon attack on the west. Front #1) sars-cov-2 + "developed" immune escape variants, front #2) ccp/pla tradecraft + fear-inducing showmanship inducing the west to use ccp/pla slow kill bioweapon spike for its countermeasure mRNA and viral vector produced vaccine antigen containing bioweapon inserts including venom sequence to create allergic reactions and essence of Staphylococcal enterotoxin B (SEB) - superantigen and a prion initiating insert linked to CJD after vaccination and in the initiation of amyloid / fibrin / platelet cascade leading to "white clots" and a moderna sequence for immune system inhibition? and ... and ...
Superantigenic character of an insert unique to SARS-CoV-2 spike supported by skewed TCR repertoire in patients with hyperinflammation
Significance
A hyperinflammatory syndrome reminiscent of toxic shock syndrome (TSS) is observed in severe COVID-19 patients, including children with Multisystem Inflammatory Syndrome in Children (MIS-C). TSS is typically caused by pathogenic superantigens stimulating excessive activation of the adaptive immune system. We show that SARS-CoV-2 spike contains sequence and structure motifs highly similar to those of a bacterial superantigen and may directly bind T cell receptors. We further report a skewed T cell receptor repertoire in COVID-19 patients with severe hyperinflammation, in support of such a superantigenic effect. Notably, the superantigen-like motif is not present in other SARS family coronaviruses, which may explain the unique potential for SARS-CoV-2 to cause both MIS-C and the cytokine storm observed in adult COVID-19.
Abstract
Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 is a newly recognized condition in children with recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. These children and adult patients with severe hyperinflammation present with a constellation of symptoms that strongly resemble toxic shock syndrome, an escalation of the cytotoxic adaptive immune response triggered upon the binding of pathogenic superantigens to T cell receptors (TCRs) and/or major histocompatibility complex class II (MHCII) molecules. Here, using structure-based computational models, we demonstrate that the SARS-CoV-2 spike (S) glycoprotein exhibits a high-affinity motif for binding TCRs, and may form a ternary complex with MHCII. The binding epitope on S harbors a sequence motif unique to SARS-CoV-2 (not present in other SARS-related coronaviruses), which is highly similar in both sequence and structure to the bacterial superantigen staphylococcal enterotoxin B. This interaction between the virus and human T cells could be strengthened by a rare mutation (D839Y/N/E) from a European strain of SARS-CoV-2. Furthermore, the interfacial region includes selected residues from an intercellular adhesion molecule (ICAM)-like motif shared between the SARS viruses from the 2003 and 2019 pandemics. A neurotoxin-like sequence motif on the receptor-binding domain also exhibits a high tendency to bind TCRs. Analysis of the TCR repertoire in adult COVID-19 patients demonstrates that those with severe hyperinflammatory disease exhibit TCR skewing consistent with superantigen activation. These data suggest that SARS-CoV-2 S may act as a superantigen to trigger the development of MIS-C as well as cytokine storm in adult COVID-19 patients, with important implications for the development of therapeutic approaches.
PLoS Biol. 2011 Sep; 9(9): e1001149.
Published online 2011 Sep 13. doi: 10.1371/journal.pbio.1001149
PMCID: PMC3172200
PMID: 21931534
Binding of Superantigen Toxins into the CD28 Homodimer Interface Is Essential for Induction of Cytokine Genes That Mediate Lethal Shock
Gila Arad,# Revital Levy,# Iris Nasie, Dalia Hillman, Ziv Rotfogel, Uri Barash, Emmanuelle Supper, Tomer Shpilka, Adi Minis, and Raymond Kaempfer *
Philippa Marrack, Academic Editor
Author information Article notes Copyright and License information Disclaimer
See "Clarifying the Mechanism of Superantigen Toxicity" in volume 9, e1001145.
This article has been corrected. See PLoS Biol. 2015 August 21; 13(8): e1002237.
Associated Data
Supplementary Materials
Go to:
Abstract
Bacterial superantigens, a diverse family of toxins, induce an inflammatory cytokine storm that can lead to lethal shock. CD28 is a homodimer expressed on T cells that functions as the principal costimulatory ligand in the immune response through an interaction with its B7 coligands, yet we show here that to elicit inflammatory cytokine gene expression and toxicity, superantigens must bind directly into the dimer interface of CD28. Preventing access of the superantigen to CD28 suffices to block its lethality. Mice were protected from lethal superantigen challenge by short peptide mimetics of the CD28 dimer interface and by peptides selected to compete with the superantigen for its binding site in CD28. Superantigens use a conserved β-strand/hinge/α-helix domain of hitherto unknown function to engage CD28. Mutation of this superantigen domain abolished inflammatory cytokine gene induction and lethality. Structural analysis showed that when a superantigen binds to the T cell receptor on the T cell and major histocompatibility class II molecule on the antigen-presenting cell, CD28 can be accommodated readily as third superantigen receptor in the quaternary complex, with the CD28 dimer interface oriented towards the β-strand/hinge/α-helix domain in the superantigen. Our findings identify the CD28 homodimer interface as a critical receptor target for superantigens. The novel role of CD28 as receptor for a class of microbial pathogens, the superantigen toxins, broadens the scope of pathogen recognition mechanisms.
Go to:
Author Summary
Induction of protective immunity involves the expression of inflammatory cytokines, proteins that mediate and respond to immune signals. However, excessive cytokine induction can lead to disease, including, at very high levels, lethal toxic shock. Staphylococcal and streptococcal superantigens are a broad family of bacterial protein toxins that induce such a lethal cytokine storm, orders of magnitude higher in intensity than that elicited during normal immune responses. A key participant in every immune response is the costimulatory receptor CD28, which forms a protein dimer to mediate the immune response. Hitherto, CD28 was not known to bind microbial components. Here, we show that superantigens co-opt CD28 as their receptor and that to induce a cytokine storm, superantigens must bind directly into the dimer interface of CD28. The interaction between CD28 and the bacterial superantigen can be blocked with peptides—short protein fragments that mimic the contact domains in the intact superantigen or in CD28. These peptides attenuate inflammatory cytokine gene induction and thus protect animals from lethal toxic shock. Our finding that CD28 is a receptor for the superantigen toxins broadens the scope of microbial pathogen recognition mechanisms and provides a novel approach for designing therapeutics that protect against toxic shock.
The United States biological weapons program officially began in spring 1943 on orders from U.S. President Franklin Roosevelt. Research continued following World War II as the U.S. built up a large stockpile of biological agents and weapons. Over the course of its 27-year history, the program weaponized and stockpiled the following seven bio-agents (and pursued basic research on many more):
I watched Dr. Chetty's original video which caused his legal problems and felt relieved that somebody was voicing my own suspicions. Most people opposed to the COVID policies blame them on greedy pharmaceutical companies and their corrupting influence on regulators, journals, universities, etc. While that was clearly a factor, I suspect there were other goals and more powerful actors at work. Probably the truth is like peeling the layers of an onion where naive doctors think the goal is saving lives and pharmaceutical executives think the goal is profit, and some sort of international organization might think the goal is saving the Earth from global warming or saving the retirement programs. Also some things may not have gone the way people hoped, so that makes discerning the goals even more difficult.
Regardless of the difficulty of discerning all the actors and their goals, it is important. As you said in the cyanide example, whoever did it will try again.
It's a shame that Dr. Chetty is having these legal problems. I hope he comes through it in good shape somehow.
When Dr. Chetty laid out his treatment protocol, one fundamental thought struck me:
Regardless of the actions initiated by politics or the pharmaceutical industry, ultimately, it is the doctor who has the power to either accept or reject the influences of politics or pharma.
I agree that ultimately doctors are supposed to have a lot of autonomy, but I'm not certan that is true in practice. As I understand it, there are protocols that protect the doctor from liability and disciplinary action, and doctors try to follow those protocols to preserve their careers.
Another factor might be locality. If a doctor has the support of his community and employers then he/she can experiment a little and find what works. I know a local chain of hospitals near my home in the US that serves small towns and has freely experimented with all sorts of COVID treatments with apparent impunity. On the other hand, in this same state of Texas, Dr Peter McCullough and Dr Richard Bartlett have had to defend themselves several times against serious legal challenges. The difference I suspect is publicity. When doctors try to spread the good news outside their supportive locality then they find serious trouble. That's all just my theory. Who knows.
I know, and you are right.
Locality and guidelines ultimately boil down to integrity and how a doctor remembers the Hippocratic Oath.
The very reason the pathogen had a low fatality rate overall and relatively higher fatality among the aged and those with preexisting illness, calls for an important role of physicians to intervene with therapeutics with evidence and proven benefits against the illness caused by the pathogen. Not following guidelines and protocols which are not benefiting their patients and recommending a vaccine which failed in its claim of preventing the transmission of the pathogen. Treating those who are vulnerable and sick rather than waiting and promoting a vaccine with no benefit of preventing the transmission is responsible and laudable clinical practice.
Therefore responsible physicians like Dr Chetty with a noble intention of healing their patients without doing no harm should be endorsed and promoted rather than targeted for scrutiny.
On the other hand those who were responsible for contributing to preventable sickness and fatalities by adopting protocols and guidelines with poor outcome stand to be targeted, scrutinised and punished. As a result of lack of professional responsibilities, ethics and conflicts of interests.
More than the virus, the deadlier cause of the pandemic havoc in 2020 and in part 2021 was the collective failure of doctors and clinicians around the world and their ignored first lesson “prevention is better than cure”. The virus gave us 8-10 days to be subdued, the viral phase, like any other respiratory virus, with a set of highly familiar symptoms. Symptoms that have been treated comprehensively and comfortably in other more benign conditions like common cold. If our medicos did not utilise that window and let the population come to grief, it is their fault not that of the virus, even after knowing what the virus was ordained to do next. To be fair, the virus has kept that window open till now and in Omicrons
has even been considerate to the humanity by almost clipping off its deadlier phase. While doctors in many countries, probably inspired by the work of the likes of Dr. Chetty on early treatments and classical medicines, used that window effectively beginning mid 2022, for the officially tutored doctors in the west that window of easy opportunity never existed, pushing the infected into the dark lanes of death. So this pandemic is not about the ways of the virus, but a tale of two sets of doctors, one never willing to remember their first lessons and another recalling that lesson mid course and changing the course of the pandemic in their populations.
Doctors , please listen to Dr Bhakdi's recent address in Germany.
https://makismd.substack.com/p/video-drsucharit-bhakdi-german-parliament?utm_source=substack&utm_medium=email&utm_campaign=email-half-post&r=o4nrz
Perhaps Dr Bhakdi's information can help the good Dr Chetty?
Thank you for this link. It is very helpful.
To bad items like Liposomal C did so much to help keep people alive.
The virus must have a pathogenic (active) part and by all evidences it is the spike protein. First and foremost, it is the one that promotes cell entry by binding to the cell surfaces. So, Dr. Chetty is right. Its origin is unknown and may never be known, denying valuable biological knowledge in service of humanity. Besides these, every other point is beyond the point. No matter what the unknown story about this virus is, Dr. Chetty himself showed that it can be tamed safely, comfortably and almost irreversibly, in its early days of infecting an individual with proven old school medicines. That is the cardinal point, picked up by thousands and thousands of doctors in many lesser countries since mid 2021 to banish the virus from their midst. That is why I will be rather charitable to the virus. It didn’t really kill millions. It is the poor clinical understanding from the doctors and medical administrations that did. Additionally in the West, the doctors were hamstrung by their administrators.
I immediately recognized Dr Shankara Chetty as a TRUE covid times HERO. I saw a picture of the parking lot covid treatment tents He had set up to See and Treat People sick with covid with REAL medical treatment for covid which PREVENTED hospitalization and death. I saw a "contrasting" picture of a fully equipped ICU covid treatment room, such as in the west, where so many of the most vulnerable were denied REAL treatment for covid and thus effectively both tortured and also actively euthanized to death by "doctors" and "nurses" directed by a evil system hell bent for power, control and money.
I AM in agreement with Dr Chetty's statements.
In the US "they" have not yet entirely removed the 1st Amendment protecting Our God Given Rights of Freedom of Religion and Speech
Amendment I
Congress shall make no law respecting an establishment of religion, or prohibiting the free exercise thereof; or abridging the freedom of speech, or of the press; or the right of the people peaceably to assemble, and to petition the government for a redress of grievances.
I would base my defense on These God Given Rights The founding Document of the United States of America, The Declaration of Independence states "We hold these truths to be self-evident, that all men are created equal, that they are endowed by their Creator with certain unalienable Rights, that among these are Life, Liberty and the pursuit of Happiness."
My "religion", Path to return to God, of 50 years informs me, that we are now engaged, As Above so below, in a battle for the future of Life On Our Planet Earth and that I Am Required to "noise this abroad".
My "religion", Path to return to God, also informs me as to the specifics, that being that God's Plan leading unto a sustainable Golden Age of Freedom and Opportunity for 9 billion people on Our Planet Earth was preempted by evil in 1998 which, in 2001, opened the door where evil dwells for the beginning of evil's plan to unfold for "their" total control, genetically engineered, depopulated, dystopian "future" for "life" on planet earth.
I see embodied evil, individually acting in pursuit of their own self interests controlling many not in the embodied evil class who do their bidding, in accordance with and in furtherance of the plans of evil at inner levels On Earth evil here and evil there - Wherever large wealth and knowledge is being created evil will be there infesting and infecting the production of that wealth and knowledge and bleeding it off to advance evil's plan for their total control, genetically engineered, dystopian, depopulated future ongoing for the majority of those remaining on "that" planet earth. The plan of evil which now increasing numbers of people across Our Earth see.
With the passage of the "patriot act" in the US after 9 11 2001 effectively all restraints on US bioweapon development were removed and development of mRNA bioweapon countermeasure technology was accelerated. This enabled the US bioweapon "complex" to create a furin cleavage site "insert" for sars-cov which provided the pandemic level of infectiousness (the 2) seen in sars-cov-2. Other bioweapon adaptable countermeasure "sequences" were patented by moderna. This and other bioweapon/bioweapon countermeasure research was "honey trapped", purchased, taken by and transfered to the ccp/pla as the ccp/pla developed it's own bioweapon "innovations".
The "chinese" "communist" party/ "people's" "liberation army bioweapon development complex located a highly virulent sars-cov with a 50% fatality rate when encapsulated within or on bat feces dust when this sars-cov transfected into 6 workers cleaning bat feces from a mine in 2013 killing 3. Of course this sars-cov immediately was sent to ccp/pla bioweapon labs for bioweapon research. In 2017 ccp/pla bioweapon researchers found a pangolin sars-cov spike evolution with exceptional human ACE2 binding affinity by searching through 3533 tissue samples taken from a small group of sick pangolins, identifying on the average, near 10 virus types in each sample to find sars-cov in tissue samples taken from pangolin #7 and in larger number from pangolin #8 and then testing these sars-cov for bioweapon potiential and finding the spike with exceptional human ACE2 binding enabling the "creation" of sars-cov-2 spike. This deduced from an evidenced, including the original then deleted supplementary data, reading of the March 22, 2020 "US" bioweapon/bioweapon countermeasure complex's "hide in plain sight" limited hangout, zoonotic origin / wet market infection epicenter, mis/dis/mal information, propaganda piece "Emergence of SARS-CoV-2 through recombination and strong purifying selection" They carefully tell some truth, always make mention of zoonotic evolution while never actually saying sars-cov-2 was zoonotic (plausible deniability) and never mention lab origin. (just look at where the authors work). This actually spelled out the US "furin cleavage site" bioweapon complex complicit, ccp/pla lab creation of sars-cov-2 - less the numbers of bioweapon "inserts" added to the "spike" of sars-cov-2.
In my defense I would present the evidence showing that the ccp/pla did what it, OF COURSE, would do.
as referenced in the below attached 2 part continued reply I previously posted as comments elsewhere.
The following is my takeaway "on a Carefully Planned Worldwide Bioweapons Attack" I originally posted this comment to a substack page discussing "DEFUSE"
DEFUSE does provides additional evidence of highly developed PREEXISTING bioweapon development work to enhance sars-cov via the addition of a furin cleavage site undertaken prior to 2018 by the US bioweapon / bioweapon and pandemic countermeasure "complex".
"The exact furin cleavage site found in SARS-CoV-2 is found in another protein, a protein called alpha-ENaC found in humans and studied heavily at the same university (UNC) as one of the PI’s of DEFUSE. "
UNC - University of North Carolina at Chapel Hill home of bioweapon baric and the bioweapon baric gain of function gang.
and then DEFUSE, based on prior knowledge writes its proposal showing that "it" has prior knowledge of the location to place the furin cleavage site to weaponize sars-cov thereby "creating" sars-cov-2. "SARS-CoV-2 has its furin cleavage site at exactly the location proposed in these grants."
It is made obvious by the outworking of events that this US developed furin cleave site and specific technology to insert it was "transfered"/taken/stolen and PRIOR to 2018 delivered to the bioweapon / bioweapon and pandemic countermeasure "complex" of the "chinese" communist party/peoples liberation army - ccp/pla.
From the Abstract of "SARS-CoV-2 and the Secret of the Furin Site" "Here we show genomic fingerprints which are specific of Pangolin-CoVs, Bat-SARS-like (CoVZC45, CoVZXC21), bat RatG13 and human SARS-CoV-2 coronaviruses. This, along with phylogenetic analysis, we found that these species have the same evolutionary origin in the bat, including a genetic recombination of S gene between Pangolin-CoV (2017) and RatG13 ancestors." RatG13 "isolated in 2013".
The following from the March 22, 2020 "US" complex "hide in plain sight" limited hangout, zoonotic origin / wet market infection epicenter, mis/dis/mal information, propaganda piece "Emergence of SARS-CoV-2 through recombination and strong purifying selection" (just look at where the authors work)
"We show evidence of strong purifying selection around the receptor binding motif (RBM) in the spike gene and in other genes among bat, pangolin and human coronaviruses, indicating similar strong evolutionary constraints in different host species. We also demonstrate that SARS-CoV-2’s entire RBM was introduced through recombination with coronaviruses from pangolins, possibly a critical step in the evolution of SARS-CoV-2’s ability to infect humans. " "we find significant recombination breakpoints before and after the ACE2 binding site (fig. S2A)," "Specifically, amino acid sequences of the receptor binding motif (RBM) in the C terminal of the S1 subunit are nearly identical to those in two Pan_SL-CoV_GD viruses, with only one amino acid difference (Q498H)—although the RBM region has not been fully sequenced in one of Guangdong pangolin virus (Pan_SL-CoV_GD/P2S)
"Thus, a functional RBM nearly identical to the one in SARS-CoV-2 is naturally present in Pan_SL-CoV_GD viruses. The very distinctive RaTG13 RBM suggests that this virus is unlikely to infect human cells, and that the acquisition of a complete functional RBM (my note; with exceptional human ACE 2 binding ability) by a RaTG13-like CoV through a recombination event with a Pan_SL-CoV_GD-like virus enabled it to use ACE2 for human infection.
note; As this "Research Article" was originally posted to the preprint? server the supplementary data initially contained a spread sheet, subsequently removed, showing on the vertical, line by line, 3533 individual tissue samples taken from a number of sick pangolins. Virus types found in each tissue sample, averaging close to 10 per sample, were listed horizontally - sars-cov was found in sick pangolin #7 and more in sick pangolin #8, more likely the "guilty party" supplying the human ACE 2 binding affinity enhancement identified in sars-cov-2.
"Furthermore, SARS-CoV-2 has a unique furin cleavage site insertion (PRRA) not found in any other CoVs in the Sarbecovirus group (24), although similar motifs are also found in MERS and more divergent bat CoVs (25) (Fig. S3). This PRRA motif makes the S1/S2 cleavage in SARS-CoV-2 much more efficiently than in SARS-CoV and may expand its tropism and/or enhance its transmissibility (23)"
Sars-cov backbone and sars-cov components were on the bioweapon lab shelves of the "chinese" communist party/people's liberation army (ccp/pla) bioweapon / bioweapon and pandemic countermeasure "complex" from 2013 - a sars-cov virus with a 50% fatality rate when transfected in aerosolized bat feces, this cov-2 supplied the "backbone" for sars-cov-2, and from 2017 a pangoplin sars-cov spike component with exceptional binding to human ACE 2.
Recombination and Strong Purifying Selection using these and using "US" furin cleavage site technology that was used to put the "2" into sars-cov, created the "pandemic" level of human to human transmission shown in sars-cov-"2".
Then this ccp/pla bioweapon complex did what it would do - develop a countermeasure vaccine and do human testing while continuing to bio weaponize their sars-cov-2, most particularly the spike*, with various bioweapon toxin inserts and virulence inhibited toxin inserts and continue to do countermeasure vaccine testing on humans. *note; Whole spike which was by that time well "noised abroad" as the choice coronavirus antigen for coding countermeasure agent mRNA.
From events we may see that during this ccp/pla bioweapon/bioweapon countermeasure development process*, in the March 2018 time frame, a virulence inhibited early sars-cov-2 began to spread across China, Asia Pacific and into areas of Chinese contact in Africa developing widespread immunity to sars-cov-2 in the population of those areas which lasted until the immunity breakthrough and increased virulence changes developed into sars-cov-2 seen in the Delta variant. see The Ethical Skeptic "China’s CCP Concealed SARS-CoV-2 Presence in China as Far Back as March 2018 https://theethicalskeptic.com/2021/11/15/chinas-ccp-concealed-sars-cov-2-presence-in-china-as-far-back-as-march-2018/
*note; The modus operandi MO of a bioweapon/bioweapon countermeasure complex is FIRST DEVELOP THE BIOWEAPON
Then a breakdown of virulence inhibition? or a leak or breakthrough infection? or a DELIBERATE DECISION to release a virulent sars-cov-2 as a stealth bioweapon attack on the west with a "pandemic" in china "GO player" cover story and THE DELIBERATE DECISION made by the ccp/pla to use all means necessary to suppress and stop the spread of covid-19 in China and THE DELIBERATE DECISION made by the ccp/pla to use all means necessary, then, to insure that that initial release sars-cov-2 spread to the world and that certain subsequent variants developed and released in "coincidental" conjunction with ccp/pla vaccine testing in foreign countries also spread, quite possibly, initially via bioweapon encapsulation to produce airborne aerosols particles , South African variant, most virulent Gamma P1 in Brazil, or spread across the world and such as Delta and then the case of Omicron. Omicron with the prion creating spike insert toxin reportedly somehow now removed. The prion creating spike insert toxin present in prior variants and replicated by mRNA in the whole spike "vaccine " antigen.
continued as a reply
This OMICRON ALLOWED TO SPREAD THROUGH CHINA reportedly doing relatively little damage to the people of China whose immune systems it appears were mostly protected from repeated infections and repeated mRMA injections creating toxic whole spike and doing other damage which made Omicron reportedly much more debilitating and killing in the multiple infection / multiple injection "west". And now, in the west, a omicron with a prion initiating site "insert" reported.
imo - All Total, fact + fact + fact, shows a ccp/pla 2 front , stealth, "unlimited war", "economic war", bioweapon attack on the west. Front #1) sars-cov-2 + "developed" immune escape variants, front #2) ccp/pla tradecraft + fear-inducing showmanship inducing the west to use ccp/pla slow kill bioweapon spike for its countermeasure mRNA and viral vector produced vaccine antigen. Induced with terrible deaths for the most vulnerable elderly and comorbid, people filmed dropping dead, staged?,on China streets. Where else in the world did we see this happening before "vaccines"? Apartment doors welded shut, massive spraying and fogging of the streets and public spaces and the phenomenal construction of hospitals in weeks which were shortly to be closed down.. Quite the show. Quite the FEAR FEAR FEAR producing show inducing the west to use "their" long planned "countermeasure" Mrna to now generate the ccp/pla bio-engineered toxic "slow kill" "spike" for its "vaccine" antigen. Infection, injection, infection, injection, infection, injection death and debilitation in the west, China largely protected with widespread prior immunity until delta with actual lock downs and conventional vaccines. "chinese" Go players vs complicit "western" checkers players.
The facts that the surveillance state ccp/pla "china" 100% knew what was circulating person to person in wuhan and 100% deliberately worked to conceal this while working to keep travel open from wuhan to the world and while they looted the "west's" stocks of N95 shows ccp/pla intent at best to "never let a good crisis go to waste" if the release was somehow not deliberate, while providing "pandemic explanation" cover with 2 "red herring" (ethical skeptic) trails 1) zoonotic origin with wet market outbreak center, to be supported by the west's complicit US bioweapon / bioweapon countermeasure / military / industrial / pharma complex, with full knowledge as to the origin of sars-cov-2, as a cover for their own complicit gain of function (gain of effect) "contribution" the furin cleavage site, the "2", the pandemic level of human to human transmission, in sars-cov-2 and other technology transferred to and taken by the ccp/pla and used by the ccp/pla for the lab recombination "creation" of sars-cov-2. Effective zoonotic "cover" for 3 years yet still being debunked leading to
"red herring" (ethical skeptic) trail 2) "ACCIDENTAL" lab release. How long for this to be debunked?
.... . evil here evil there - evil won round "covid"
a ccp/pla 2 front , stealth, "unlimited war", "economic war", bioweapon attack on the west. Front #1) sars-cov-2 + "developed" immune escape variants, front #2) ccp/pla tradecraft + fear-inducing showmanship inducing the west to use ccp/pla slow kill bioweapon spike for its countermeasure mRNA and viral vector produced vaccine antigen containing bioweapon inserts including venom sequence to create allergic reactions and essence of Staphylococcal enterotoxin B (SEB) - superantigen and a prion initiating insert linked to CJD after vaccination and in the initiation of amyloid / fibrin / platelet cascade leading to "white clots" and a moderna sequence for immune system inhibition? and ... and ...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082696/pdf/main.pdf#bib40
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082696/
Article
A monoclonal antibody against staphylococcal
enterotoxin B superantigen inhibits SARS-CoV-2
entry in vitro
Article
A monoclonal antibody against staphylococcal
enterotoxin B superantigen inhibits
SARS-CoV-2 entry in vitro
Mary Hongying Cheng, 1 Rebecca A. Porritt, 2,3 Magali Noval Rivas, 2,3 James M. Krieger, 1 Asli Beyza Ozdemir,2,3
Gustavo Garcia, Jr., 4,5 Vaithilingaraja Arumugaswami, 4,5 Bettina C. Fries, 6,7 Moshe Arditi,2,3,8, * and Ivet Bahar1,8,9, *
1Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA
2Department of Pediatrics, Division of Pediatric Infectious Diseases and Immunology, Cedars-Sinai Medical Center, Los Angeles, CA
90048, USA
3Biomedical Sciences, Infectious and Immunologic Diseases Research Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
4Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles,
CA 90095, USA
5Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA
90095, USA
6Department of Medicine, Stony Brook University Hospital, Stony Brook, New York, NY 11794, USA
7Northport VA Medical Center, Northport, NY 11768, USA
8These authors contributed equally
9Lead contact
*Correspondence: moshe.arditi@cshs.org (M.A.), bahar@pitt.edu (I.B.)
https://doi.org/10.1016/j.str.2021.04.005
SUMMARY
We recently discovered a superantigen-like motif sequentially and structurally similar to a staphylococcal
enterotoxin B (SEB) segment, near the S1/S2 cleavage site of the SARS-CoV-2 spike protein, which might
explain the multisystem inflammatory syndrome (MIS-C) observed in children and the cytokine storm in se-
vere COVID-19 patients. We show here that an anti-SEB monoclonal antibody (mAb), 6D3, can bind this viral
motif at its polybasic (PRRA) insert to inhibit infection in live virus assays. The overlap between the superanti-
genic site of the spike and its proteolytic cleavage site suggests that the mAb prevents viral entry by inter-
fering with the proteolytic activity of cell proteases (furin and TMPRSS2). The high affinity of 6D3 for this
site originates from a polyacidic segment at its heavy chain CDR2. The study points to the potential utility
of 6D3 for possibly treating COVID-19, MIS-C, or common colds caused by human coronaviruses that also
possess a furin-like cleavage site.
Loss of furin cleavage site attenuates SARS-CoV-2 pathogenesis
https://www.pnas.org/doi/10.1073/pnas.2010722117
Superantigenic character of an insert unique to SARS-CoV-2 spike supported by skewed TCR repertoire in patients with hyperinflammation
Significance
A hyperinflammatory syndrome reminiscent of toxic shock syndrome (TSS) is observed in severe COVID-19 patients, including children with Multisystem Inflammatory Syndrome in Children (MIS-C). TSS is typically caused by pathogenic superantigens stimulating excessive activation of the adaptive immune system. We show that SARS-CoV-2 spike contains sequence and structure motifs highly similar to those of a bacterial superantigen and may directly bind T cell receptors. We further report a skewed T cell receptor repertoire in COVID-19 patients with severe hyperinflammation, in support of such a superantigenic effect. Notably, the superantigen-like motif is not present in other SARS family coronaviruses, which may explain the unique potential for SARS-CoV-2 to cause both MIS-C and the cytokine storm observed in adult COVID-19.
Abstract
Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 is a newly recognized condition in children with recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. These children and adult patients with severe hyperinflammation present with a constellation of symptoms that strongly resemble toxic shock syndrome, an escalation of the cytotoxic adaptive immune response triggered upon the binding of pathogenic superantigens to T cell receptors (TCRs) and/or major histocompatibility complex class II (MHCII) molecules. Here, using structure-based computational models, we demonstrate that the SARS-CoV-2 spike (S) glycoprotein exhibits a high-affinity motif for binding TCRs, and may form a ternary complex with MHCII. The binding epitope on S harbors a sequence motif unique to SARS-CoV-2 (not present in other SARS-related coronaviruses), which is highly similar in both sequence and structure to the bacterial superantigen staphylococcal enterotoxin B. This interaction between the virus and human T cells could be strengthened by a rare mutation (D839Y/N/E) from a European strain of SARS-CoV-2. Furthermore, the interfacial region includes selected residues from an intercellular adhesion molecule (ICAM)-like motif shared between the SARS viruses from the 2003 and 2019 pandemics. A neurotoxin-like sequence motif on the receptor-binding domain also exhibits a high tendency to bind TCRs. Analysis of the TCR repertoire in adult COVID-19 patients demonstrates that those with severe hyperinflammatory disease exhibit TCR skewing consistent with superantigen activation. These data suggest that SARS-CoV-2 S may act as a superantigen to trigger the development of MIS-C as well as cytokine storm in adult COVID-19 patients, with important implications for the development of therapeutic approaches.
PLoS Biol. 2011 Sep; 9(9): e1001149.
Published online 2011 Sep 13. doi: 10.1371/journal.pbio.1001149
PMCID: PMC3172200
PMID: 21931534
Binding of Superantigen Toxins into the CD28 Homodimer Interface Is Essential for Induction of Cytokine Genes That Mediate Lethal Shock
Gila Arad,# Revital Levy,# Iris Nasie, Dalia Hillman, Ziv Rotfogel, Uri Barash, Emmanuelle Supper, Tomer Shpilka, Adi Minis, and Raymond Kaempfer *
Philippa Marrack, Academic Editor
Author information Article notes Copyright and License information Disclaimer
See "Clarifying the Mechanism of Superantigen Toxicity" in volume 9, e1001145.
This article has been corrected. See PLoS Biol. 2015 August 21; 13(8): e1002237.
Associated Data
Supplementary Materials
Go to:
Abstract
Bacterial superantigens, a diverse family of toxins, induce an inflammatory cytokine storm that can lead to lethal shock. CD28 is a homodimer expressed on T cells that functions as the principal costimulatory ligand in the immune response through an interaction with its B7 coligands, yet we show here that to elicit inflammatory cytokine gene expression and toxicity, superantigens must bind directly into the dimer interface of CD28. Preventing access of the superantigen to CD28 suffices to block its lethality. Mice were protected from lethal superantigen challenge by short peptide mimetics of the CD28 dimer interface and by peptides selected to compete with the superantigen for its binding site in CD28. Superantigens use a conserved β-strand/hinge/α-helix domain of hitherto unknown function to engage CD28. Mutation of this superantigen domain abolished inflammatory cytokine gene induction and lethality. Structural analysis showed that when a superantigen binds to the T cell receptor on the T cell and major histocompatibility class II molecule on the antigen-presenting cell, CD28 can be accommodated readily as third superantigen receptor in the quaternary complex, with the CD28 dimer interface oriented towards the β-strand/hinge/α-helix domain in the superantigen. Our findings identify the CD28 homodimer interface as a critical receptor target for superantigens. The novel role of CD28 as receptor for a class of microbial pathogens, the superantigen toxins, broadens the scope of pathogen recognition mechanisms.
Go to:
Author Summary
Induction of protective immunity involves the expression of inflammatory cytokines, proteins that mediate and respond to immune signals. However, excessive cytokine induction can lead to disease, including, at very high levels, lethal toxic shock. Staphylococcal and streptococcal superantigens are a broad family of bacterial protein toxins that induce such a lethal cytokine storm, orders of magnitude higher in intensity than that elicited during normal immune responses. A key participant in every immune response is the costimulatory receptor CD28, which forms a protein dimer to mediate the immune response. Hitherto, CD28 was not known to bind microbial components. Here, we show that superantigens co-opt CD28 as their receptor and that to induce a cytokine storm, superantigens must bind directly into the dimer interface of CD28. The interaction between CD28 and the bacterial superantigen can be blocked with peptides—short protein fragments that mimic the contact domains in the intact superantigen or in CD28. These peptides attenuate inflammatory cytokine gene induction and thus protect animals from lethal toxic shock. Our finding that CD28 is a receptor for the superantigen toxins broadens the scope of microbial pathogen recognition mechanisms and provides a novel approach for designing therapeutics that protect against toxic shock.
https://en.wikipedia.org/wiki/United_States_biological_weapons_program
United States biological weapons program
The United States biological weapons program officially began in spring 1943 on orders from U.S. President Franklin Roosevelt. Research continued following World War II as the U.S. built up a large stockpile of biological agents and weapons. Over the course of its 27-year history, the program weaponized and stockpiled the following seven bio-agents (and pursued basic research on many more):
Bacillus anthracis (anthrax)
Francisella tularensis (tularemia)
Brucella spp (brucellosis)
Coxiella burnetii (Q-fever)
Venezuelan equine encephalitis virus
Botulinum toxin (botulism)
Staphylococcal enterotoxin B