From the beginning, a characteristic of SARS-CoV-2, the virus responsible for the Covid-19 disease, stood out. The virus had a furin cleavage site (FCS) that allowed it to infect humans. In the circle of relatives of coronaviruses to which SARS-CoV-2 belongs, SARS-CoV-2 is only one of more than 800 viruses affected by 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 worked on coronaviruses right up to the outbreak in 2019. We are also aware of the DEFUSE proposal under which Wuhan-based scientists and their US collaborators sought 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 National Institutes of Health (NIH) funding, the Wuhan Institute of Virology (WIV) constructed genetically modified SARS coronaviruses that combined the spike gene from one bat SARS-related coronavirus with the rest of the genetic information from another bat SARS-related coronavirus, obtaining new viruses that efficiently infected and replicated in human cells, and obtaining at least one new virus that exhibited 10,000 times enhanced viral growth in lungs, 1,000,000 times enhanced viral growth in brains, and three times enhanced lethality in humanized mice.
In 2018, just a year before the pandemic, as part of an NIH grant proposal, the Wuhan Institute of Virology and collaborators proposed constructing other genetically modified SARS coronaviruses, proposing to construct spiked viruses with higher binding affinities. by human SARS receptors, hypothesizing that such viruses would have greater pandemic potential.
Moreover, in 2018, just one year before the pandemic, in a Defense Advanced Research Projects Agency (DARPA) grant proposal, the Wuhan Institute of Virology and its collaborators proposed to construct genetically modified SARS coronaviruses having a “furin cleavage site” a feature associated with increased viral growth and increased transmissibility — inserted at the spike ‘S1-S2’ border and to construct these viruses by synthesising six nucleic-acid building blocks and assembling the six nucleic-acid building blocks using the reagent ‘BsmBI’.
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 the more than 800 known SARS-related coronaviruses that has a furin cleavage site. Mathematically, this fact implies that the probability of finding a SARS-related herbal coronavirus with a furin cleavage site is less than 1 in 800.
The SARS-CoV-2 furin cleavage site has a codon usage (the bias of personal tastes between three sets of synonymous nucleotides that encode amino acids in the genetic code) that is very high for a natural SARS-related coronavirus , but it is expected for a series designed for paintings on humans.
Altogether, the presence of a peak with an incredibly high affinity for human SARS receptors, the presence of a furin cleavage site at the S1-S2 boundary of the spike, the use of furin cleavage site codons, the characteristics of the series that allow the reunion of six building blocks of artificial nucleic acid with BsmBI as the reagent for the reunion, and the one-to-one correspondence between those features and the features proposed in the 2018 NIH and DARPA’s proposals make an incredibly strong argument: “compelling evidence” for a research-related origin.
Gain-of-function (GoF) studies have been at the center of 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 common ground is needed when it comes to GoF studies or should it be stopped or significantly reduced as the risks far outweigh the potential benefits?
As far as gain-of-function studies go, these are about creating new threats to fitness, threats that didn’t exist before and likely wouldn’t exist through herbal 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.
Fear gain-of-function studies pose significant dangers by creating potential new or advanced pandemic pathogens. If a potential new pandemic pathogen is released into humans, whether deliberately or not, it can cause a pandemic.
Fear gain-of-function studies present data dangers by providing insights into the structure and homes of potential new pandemic pathogens. The study publication provides step-by-step commands (“recipes”) that can be used by a rogue nation, organization, or individual to construct a potential 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.
The gain-of-function research of concern provides limited benefits.
The Gain-of-function research of concern has no civilian practical applications. In particular, the gain of-function research of concern is not needed for, and does not contribute to, the development of vaccines and drugs — companies develop vaccines and drugs against pathogens that exist and circulate in humans and not against pathogens that do not yet exist and do not yet circulate in humans.
The gain-of-function research of concern is a small part of biomedical research — less than 0.1 per cent of all biomedical research and less than 1 per cent of virology.
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.
Fear gain-of-function studies should be prohibited or, at a minimum, be subject to independent and transparent oversight at home or abroad to ensure that a risk-benefit assessment is carried out before the start of the studies. , obtain profiles of advantages are acceptable and mitigable dangers 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, calculated that the chance of SARS-CoV-2 developing furin cleavage sites at the exact spot that it did in nature is one in 1.2 billion. Do you agree with the assessment that an ancestor virus evolving into SARS-CoV-2 naturally —with furin cleave sites in the spike protein— is so narrow that it’s next to impossible as Mr Quay noted?
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 codon usage —the pattern of preferences among synonymous three nucleotide sequences encoding amino acids in the genetic code— that is highly unusual for a bat SARS-related coronavirus. The FCS of SARS-CoV-2 contains two consecutive CGG codons where CGG is one of six synonymous codons for the amino acid arginine, and is used rarely —as less than 1 in 30 codons for arginine— in bat SARS-related coronaviruses, but is used frequently in humans (58).
Mathematically, the probability of finding a SARS-related herbal coronavirus that has two consecutive CGG codons is less than 1 in 30 (P
Mathematically, the combined odds of finding a SARS-related herbal coronavirus possessing one FCS and two consecutive CGG codons are less than 1 in 24,000 to less than 1 in 720,000.
This leads me to another question which I have thought of numerous times while reading about this virus. For my benefit and that of our readers, most of whom are not scientists, please tell us your assessment that if this virus did not have furin cleavage sites, do you think the virus would still have the potential to cause a worldwide pandemic?
Unlikely.
What is it like to know conclusively the origin of the Covid-19 pandemic?Is this just a matter of duty or a search for answers, or is there something more important at stake?
In the wake of any disaster —a train derailment, a plane crash, a rocket explosion, a reactor meltdown, a terror attack or a war— the causes of the disaster are investigated and the findings are used to inform policy changes to reduce the risks and the impacts of future disasters.
The same will have to be done after the Covid-19 disaster.
As a scientist, what pushed you to look into the possibility of the laboratory-origin of SARS-CoV-2? Considering that most of the scientists trusted their fellow scientists advocating the natural-origin view, such as those who published the infamous ‘Proximal Origin’ paper, how did you start pursuing a different trail? Did you start as a skeptic or did you suspect lab-leak from the onset?
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 completely transparent about the coronavirus outbreak, for example by sharing relevant data 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 appears likely, they knew before January 2020 that lab release had occurred.
Do you think acceptance in science and scientists has decreased especially since the start of the Covid-19 pandemic?
Yes. Absolutely.
In the past five years, we have seen how not just Chinese scientists but Western scientists misled the public about the reality of the outbreak. Even as they privately suspected lab-accident or lab-engineering, they publicly pushed for the natural-origin narrative. Moreover, the public guidance issued by scientists and the way the World Health Organization (WHO) shared the Chinese narrative made people question if the experts know any better than the average person on the street.
Have you, scientists and institutions like the WHO, lost the stature you once had?
Yes. Absolutely.
As for the Covid-origin, we have had numerous investigations, such as the Biden administration’s intelligence review and Congressional investigations. However, several experts, such as Robert Moffit of the Heritage Foundation in a previous interview with me, have said that there needs to be a 9/11 Commission-type bipartisan inquiry into Covid-origin. Do you agree?
Of course, we will have to pay attention to the composition of said commission. It cannot come from those who have defrauded the public in this regard.
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 action has been taken – none – in the face of the dangers of a long-term laboratory-generated pandemic.