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, this phenomenon is rare.
However, there is now compelling evidence that such a trait evolved in the laboratory, says Richard Ebright, a molecular biologist at Rutgers University.
Ebright, a professor of chemistry and chemical biology on the Rutgers Board of Trustees and laboratory director at the Waksman Institute for Microbiology, also discusses the benefits of functional studies, dicy studies in which scientists assign characteristics to pathogens that they do have naturally, and says such paints have no practical civilian utility. 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 have 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 superior binding affinities for human SARS receptors, hypothesizing. that such viruses would have greater pandemic potential.
Moreover, 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 to build genetically modified SARS coronaviruses with a “furin cleavage site. “”a feature related to increased viral expansion and increased transmissibility, inserted at the limit of the ‘S1-S2’ peak and to build those viruses by synthesizing six nucleic acid building blocks and assembling all six. the basic components of nucleic acid are the reagent “BsmBI”.
In 2019, a novel SARS-related coronavirus having a spike with extremely high binding affinity for human SARS receptors, a furin cleavage site at the spike S1-S2 border, and a genome sequence with features enabling assembly from six synthetic nucleic-acid building blocks using BsmBI as a reagent for assembly —a virus having the exact features proposed in the 2018 NIH and DARPA proposals—emerged on the doorstep of the Wuhan Institute of 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 as expected for a series designed for paintings in humans.
Taken together, the presence of a spike with incredibly high affinity for human SARS receptors, the presence of a furin cleavage site at the S1-S2 boundary of the spike, the codon usage of the furin cleavage site, the series features that enable assembly of six artificial nucleic acid building blocks with BsmBI as reagent for assembly, and the one-to-one correspondence between those features and the features proposed in the 2018 NIH and DARPA proposals constitute a incredibly strong argument: “compelling evidence” of 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 studies on GoF or whether it should be stopped or reduced especially since the dangers far outweigh the possible 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 pose significant (existential) risks. The gain-of-function studies we are concerned about present informational risks.
Gain-of-function studies pose significant dangers by creating new or advanced pandemic pathogens. If a potential new pandemic pathogen is released into humans, either deliberately or voluntarily, 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.
The gain-of-function research likely caused the Covid-19 pandemic and surely could cause the next pandemic.
As for gain of function, there are limited benefits.
The related gain-of-function studies have no civilian practical application. In particular, gain-of-function studies of fear are unnecessary and do not contribute to the progression of vaccines and drugs: corporations are developing vaccines and drugs that oppose pathogens that exist and circulate in humans and not pathogens that are not yet present, exist, and not yet circulate in humans.
Fear gain-of-function studies represent a small portion of biomedical studies: less than 0. 1% of all biomedical studies and less than 1% of virology studies.
As the gain-of-function research of concern poses high —potentially existential— risks and provides limited benefits, the risk-benefit ratio for the research almost always is extremely unfavourable.
Gain-of-function studies should be prohibited or, at least, be subject to independent and transparent control, national or foreign, which ensures that, before starting the studies, a risk-benefit evaluation is carried out, that the risk-benefit evaluation that profiles are appropriate and that mitigable hazards are mitigated.
What do you think so far of biodefense programs, such as PREDICT? Do you think these programs, as well as activities like GoF research, introduced with the concept of identification and detection of pandemic-causing pathogens, have worked well so far? Or that the concept itself is misplaced?
PREDICT and its successor programs have been an utter failure. They have not generated any – 0 – data useful to save you from pandemics or respond to pandemics. They caused the Covid-19 pandemic, killed more than 20 million people, and cost more than $25 trillion. They are about to cause pandemics in the long term.
One scientist, Steven Quay, calculated that the number of SARS-CoV-2 that appears at furin cleavage sites in the exact place it did in the wild 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 on the spike protein) is so limited that it is nearly impossible, as Mr. Quay noted?
The SARS-CoV-2 is the only one of more than 800 known SARS-related coronaviruses —sarbecoviruses— that possesses a furin cleavage site (FCS). Mathematically, this finding by itself implies that the probability of encountering a natural SARS-related coronavirus possessing 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 (such as less than 1 in 30 codons for arginine) in coronaviruses related to SARS in bats. it is still used 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 < 0. 05); assuming a non-independent range of codons for the two codon positions – within 1 in 9,000 – P < 0. 005; assuming a variety of independent codons for the two codon positions.
Mathematically, the combination of finding a SARS-related herbal coronavirus with an FCS and two consecutive CGG codons is 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?
Improbable.
What is it like to know conclusively the origin of the Covid-19 pandemic?Is it just a matter of duty or locating answers, or is there something else at stake?
After a crisis (an exercise derailment, plane crash, rocket explosion, reactor meltdown, terrorist attack, or war), the reasons for the crisis are investigated. Research and outcomes are used to indicate policy adjustments to reduce risk. and the effects of long-term crises.
The same will have to be done after 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 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?
Especially if, as is likely, they knew before January 2020 that the release had taken place in the laboratory.
Do you think acceptance in science and scientists has decreased especially since the start of the Covid-19 pandemic?
Yes. Absolutely.
Over the past five years, we have noticed how not only Chinese but also Western scientists misled the public about the truth of the outbreak. Even when they privately suspected a laboratory accident or laboratory engineering, they publicly pushed the narrative of natural origin. In addition, the public guidance issued by the scientists and the way the World Health Organization (WHO) shared the Chinese narrative made experts know more than the average user on the street.
Have you, scientists and institutions like the WHO, lost the stature you once had?
Yes. Absolutely.
Regarding the origin of Covid, we have had many 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 a bipartisan 9/11 Commission-style investigation into the origins of Covid is needed. 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 action has been taken – none – in the face of the dangers of a long-term laboratory-generated pandemic.