From the onset, one feature of SARS-CoV-2, the virus that causes Covid-19 disease, stood out. The virus had a furin cleavage site (FCS) that allowed it to infect humans. In the family of coronaviruses to which SARS-CoV-2 belongs, the SARS-CoV-2 is only one of more than 800 viruses with FCS.
In nature, such an occurrence is extremely rare.
However, there is now compelling evidence that such a feature evolved in the lab, explains Richard Ebright, a molecular biologist at Rutgers University.
Ebright, the Board of Governors Professor of Chemistry and Chemical Biology at Rutgers and Laboratory Director at the Waksman Institute of Microbiology, also discusses the gain of function research, the risky research in which scientists give characteristics to pathogens that they do not naturally have, and says such work has no practical civilian usage. Edited excerpts:
Five years after the Covid-19 outbreak, we know that Chinese scientists had the closest known ancestor of SARS-CoV-2 with them and had been working with coronaviruses until the 2019 outbreak. We are also aware of the DEFUSE proposal according to which Wuhan scientists and their American collaborators attempted to insert furin cleavage sites into coronaviruses.
Do you think that the DEFUSE proposal is the irrefutable evidence that we are to relate to the origin of Covid-19?
In 2017-2018, with investment from the National Institutes of Health (NIH), the Wuhan Institute of Virology (WIV) constructed genetically modified SARS coronaviruses that combined the Spike gene from a bat coronavirus related to SARS. mouse with the rest of the genetic data of some other bat. The SARS-related coronavirus, obtaining new viruses that successfully infect and reflect in human cells, and obtaining at least one new virus with a 10,000-fold viral expansion in the lungs, a viral expansion in the brain higher by a million and a lethality three times higher in humanized mice. .
In 2018, just a year before the pandemic, as part of an NIH grant proposal, the Wuhan Institute of Virology and its collaborators proposed building more genetically modified SARS coronaviruses, proposing to build viruses with spikes that had binding affinities. by human SARS receptors, hypothesizing that such viruses would have greater pandemic potential.
Furthermore, in 2018, just a year before the pandemic, as part of a grant proposal from the Defense Advanced Research Projects Agency (DARPA), the Wuhan Institute of Virology and its collaborators proposed the construction of SARS coronavirus genetically modified organisms that had a “furin cleavage site. ” ‘, a characteristic related to greater viral expansion and greater transmissibility, inserted at the ‘S1-S2’ peak boundary and to construct those viruses by synthesizing six constituent elements of the nucleic acid and assembling the six of the constituent elements of the nucleic acid the “BsmBI” reagent.
In 2019, a novel SARS-related coronavirus shows a spike with an incredibly high binding affinity for human SARS receptors, a furin cleavage site at the boundary of the S1-S2 spike, and a genomic series with features that allow the binding of six building blocks of artificial nucleic acids. acid. BsmBI as a reagent of reunion, a virus with the precise characteristics proposed in the 2018 NIH and DARPA proposals, appeared on the doors of the Wuhan Institute. Virology.
SARS-CoV-2 is the only one of more than 800 known SARS-related coronaviruses that possesses a furin cleavage site. Mathematically, this fact by itself implies that the probability of encountering a natural SARS-related coronavirus possessing a furin cleavage site is less than 1 in 800.
The furin cleavage site of SARS-CoV-2 has a use of codons (the tendency of personal tastes between three series of synonymous nucleotides that encode amino acids in the genetic code) that is very high for a natural SARS-related coronavirus, but is expected for a series designed for paintings in humans.
Taken together, the presence of a spike having an extremely high affinity for human SARS receptors, the presence of a furin cleavage site at the spike S1-S2 border, the unusual codon usage of the furin cleavage site, the sequence features enabling assembly from six synthetic nucleic-acid building blocks with BsmBI as reagent for assembly, and the one-for-one match between these features and the features proposed in the 2018 NIH and DARPA proposals, make an extremely strong case —a ‘smoking gun’ for a research related origin.
Gain of service (GoF) studies have been at the center of the Covid-19 discourse in the laboratory. What do you make of the insistence of some scientists that GoF studies will have to continue and are essential? Do you think a middle ground is needed regarding GoF studies or whether it should be stopped or reduced especially since the dangers far outweigh the possible benefits?
The gain-of-function research of concern involves the creation of new health threats — health threats that did not exist previously and that might not come to exist by natural means for tens, hundreds, thousands, or tens of thousands of years.
Gain-of-function studies present significant (existential) dangers. Gain-of-function studies present pitfalls and informational hazards.
Gain-of-function studies pose significant dangers by creating new or advanced potential pandemic pathogens. If a potential new pandemic pathogen is released into humans, either deliberately or otherwise, it can cause a pandemic.
Gain-of-function studies pose data risks by providing data on the structure and locations of potential new pandemic pathogens. The study publication provides commands – step-by-step “recipes” – that can be used by a rogue nation, organization or individual to construct a possible new pandemic pathogen and release it to cause a pandemic.
Gain-of-function studies likely caused the Covid-19 pandemic and may cause the next pandemic.
Gain of function considerations offer limited benefits.
Studies related to gain-of-function have no practical civil application. In particular, gain-of-function studies of fear are unnecessary and do not contribute to the advancement of vaccines and drugs: corporations are developing vaccines and drugs that oppose pathogens that exist and circulate in humans, not pathogens that are not yet present. they exist and do not yet circulate in humans.
Gain-of-function studies that raise considerations represent a small portion of biomedical studies: less than 0. 1% of all biomedical studies and less than 1% of virology studies.
Because gain-of-function studies carry significant (potentially existential) dangers and offer limited benefits, the risk/benefit ratio of the studies is almost incredibly unfavorable.
The gain-of-function research of concern should be banned or, at absolute minimum, should be subject to independent and transparent national- or international-level oversight that ensures that, before research is started, risk-benefit assessment is performed, risk-benefit profiles are acceptable, and mitigable risks are mitigated.
What is your opinion on biodefense programs, such as PREDICT? Do you think such programs, as well as activities like GoF research, introduced with the concept of identifying and preparing for pandemic-causing pathogens, have worked well? Is the concept itself misplaced?
PREDICT and the systems that followed it were an absolute failure. They generated 0 – 0 – useful data to prevent or respond to pandemics. They caused the Covid-19 pandemic, killing more than 20 million people and costing more than $25 trillion. They are about to cause long-term pandemics.
One scientist, Steven Quay, estimated that the number of SARS-CoV-2 appearing at furin cleavage sites in the exact place it did in nature is one in 1. 2 billion. Do you agree with the assessment that a naturally evolved SARS-CoV-2 ancestor virus (with furin cleavage sites in the spike protein) is so limited as to be almost impossible, as Mr Quay pointed out?
SARS-CoV-2 is the only one among more than 800 known SARS-related coronaviruses (sarbecovirus) that possesses a furin cleavage site (FCS). Mathematically, this result implies that the probability of finding a SARS-related herbal coronavirus with an FCS is less than 1 in 800 (P < 0. 005).
The FCS of SARS-CoV-2 has a codon usage (the trend of personal tastes between three synonymous nucleotide sequences that encode amino acids in the genetic code) that is very unusual for a bat SARS-related coronavirus. The FCS of SARS-CoV-2 comprises two consecutive CGG codons, where CGG is one of six codons synonymous with the amino acid arginine, and is rarely used (e. g. , less than 1 in 30 codons for arginine) in related coronaviruses. with SARS in bats. , is still used in humans (58).
Mathematically, the probability of encountering a natural SARS-related coronavirus having two consecutive CGG codons is less than 1 in 30 —P < 0.05; assuming non-independent codon selection for the two codon positions— to less than 1 in 9,000 — P < 0.005; assuming independent codon selection for the two codon positions.
Mathematically, the combined odds of finding a SARS-related herbal coronavirus possessing an FCS and two consecutive CGG codons are less than 1 in 24,000 to less than 1 in 720,000.
This leads me to wonder about what I have idea about several times while reading about this virus. To my advantage and those of our readers, most of whom are not scientists, please tell us your assessment that if this virus had no skin cleavage sites, do you think it would still have a chance of causing a global pandemic?
Unlikely.
What is it like to know conclusively the origin of the Covid-19 pandemic?Is it just a matter of duty or the search for answers, or is there something more important at stake?
After a crisis (a workout derailment, a plane crash, a rocket explosion, a reactor meltdown, a terrorist attack, or a war), the reasons for the crisis are investigated and the effects are used to determine the risk of policy adjustments. the effects of long-term crises.
The same needs to be done in the wake of the Covid-19 disaster.
As a scientist, what prompted you to investigate the option of a laboratory origin of SARS-CoV-2?Knowing that most scientists trusted their scientific colleagues who held the view of natural origin, such as those who published the famous article on “proximate origin”. How did you start down another path? Did you start out skeptical or suspected a lab leak from the start?
All informed persons —without exception— knew by early 2020 that a laboratory origin of Covid-19 was more likely than not, but most chose to lie for five years.
If Chinese researchers and their American collaborators had been absolutely transparent about the coronavirus outbreak, for example by sharing relevant information from databases and making the genome public, do you think the world could have responded better to the Covid-19 pandemic?
Yes. Especially if, as is likely, they knew before January 2020 that the laboratory release had occurred.
Do you believe the trust in science and scientists has fallen considerably since the outbreak of the Covid-19 pandemic?
Yes. Absolutely.
Over the past five years, we have watched as not only Chinese but also Western scientists have misled the public about the truth of the epidemic. Although privately suspected a twist of fate or laboratory engineering, they publicly pushed the narrative of the herbs’ origins. In addition, public guidance released through scientists and the way the World Health Organization (WHO) has shared the Chinese narrative have left other people wondering if experts know more than the average user on streetArray.
Do you think scientists and establishments like the WHO have lost the stature they once had?
Yes. Absolutely.
As for the origin of Covid, we’ve had a lot of investigations, such as the Biden administration’s intelligence review and congressional investigations. However, a number of experts, such as Robert Moffit of the Heritage Foundation in a previous interview with me, have said that they wish there was a bipartisan 9/11 Commission-style inquiry into the origins of Covid. Do you agree?
Yes. However, attention will have to be paid to the composition of said commission. He cannot come with those who defrauded the public in this matter.
Five years after the Covid-19 pandemic, is the world more prepared to face a new epidemic with a pandemic perspective in the future?
No, no one has been found guilty of the Covid-19 pandemic and no measures – none – have been taken to address the dangers of a long-lasting laboratory-generated pandemic.