UPDATE 22. June 2021: Is CoronaVirus the product of twenty years of battlefield testing?


UPDATE 09. June 2021: Smoking gun: Wuhan collaborator Peter Daszak admits to developing “killer” coronaviruses with communist Chinese

UPDATE 08. June 2021: WATCH: Explosive, Unearthed Video Shows Peter Daszak Describing ‘Chinese Colleagues’ Developing ‘Killer’ Coronaviruses.

UPDATE 04. June 2021: Dr. Fauci Attacked Trump for Lab Leak Theory Despite Not Having Access to the Intelligence

UPDATE 31. May 2021: Smoking gun: Communist China plans to fight WWIII with bioweapons

UPDATE 22. Mai 2021: China virus ‘smoking gun’ found

UPDATE 16. May 2021: U.S. Dem Committee Chair Calls For COVID Origins Investigation Considering ‘Every Hypothesis Available.’

UPDATE 15. May 2021: "The Canadian Connection" with Special Guest, David Hawkins, and host, Jason Goodman

ICYMI: INDEPENDENT STUDY CONCLUDES SARS-CoV-2 IS MAN-MADE - The genetic structure of SARS‐CoV‐2 does not rule out a laboratory origin

PROLOGUE: UNfortunately the author ,Nicholas Wade, though he made a considerable effort to look at the question he investigated from all sides, failed to dig just a little bit deeper – especially into the findings of the WHO/UN report. But then, such would have made it impossible for him to write this rather diplomatic piece, though he comes to the same conclusion as others, who were more hard hitting in bringing out the truth. However, also this publication dismisses any possibility of a natural origin and with this that cheap escape route for those responsible should be closed now for good. The trap-doors must close now to nab the culprits of this bioterror.

Did people or nature open Pandora’s box at Wuhan?

The spike proteins on the coronavirus’s surface determine which animal it can infect. CDC.gov

By Nicholas Wade - 30. April 2021

The Covid-19 pandemic has disrupted lives the world over for more than a year. Its death toll will soon reach three million people. Yet the origin of pandemic remains uncertain: the political agendas of governments and scientists have generated thick clouds of obfuscation, which the mainstream press seems helpless to dispel.

In what follows I will sort through the available scientific facts, which hold many clues as to what happened, and provide readers with the evidence to make their own judgments. I will then try to assess the complex issue of blame, which starts with, but extends far beyond, the government of China.

By the end of this article, you may have learned a lot about the molecular biology of viruses. I will try to keep this process as painless as possible. But the science cannot be avoided because for now, and probably for a long time hence, it offers the only sure thread through the maze.

The virus that caused the pandemic is known officially as SARS-CoV-2, but can be called SARS2 for short. As many people know, there are two main theories about its origin. One is that it jumped naturally from wildlife to people. The other is that the virus was under study in a lab, from which it escaped. It matters a great deal which is the case if we hope to prevent a second such occurrence.

I’ll describe the two theories, explain why each is plausible, and then ask which provides the better explanation of the available facts. It’s important to note that so far there is no direct evidence for either theory. Each depends on a set of reasonable conjectures but so far lacks proof. So I have only clues, not conclusions, to offer. But those clues point in a specific direction. And having inferred that direction, I’m going to delineate some of the strands in this tangled skein of disaster.

A Tale of Two Theories

After the pandemic first broke out in December 2019, Chinese authorities reported that many cases had occurred in the wet market — a place selling wild animals for meat — in Wuhan. This reminded experts of the SARS1 epidemic of 2002 in which a bat virus had spread first to civets, an animal sold in wet markets, and from civets to people. A similar bat virus caused a second epidemic, known as MERS, in 2012. This time the intermediary host animal was camels.

The decoding of the virus’s genome showed it belonged a viral family known as beta-coronaviruses, to which the SARS1 and MERS viruses also belong. The relationship supported the idea that, like them, it was a natural virus that had managed to jump from bats, via another animal host, to people. The wet market connection, the only other point of similarity with the SARS1 and MERS epidemics, was soon broken: Chinese researchers found earlier cases in Wuhan with no link to the wet market. But that seemed not to matter when so much further evidence in support of natural emergence was expected shortly.

Wuhan, however, is home of the Wuhan Institute of Virology, a leading world center for research on coronaviruses. So the possibility that the SARS2 virus had escaped from the lab could not be ruled out. Two reasonable scenarios of origin were on the table.

From early on, public and media perceptions were shaped in favor of the natural emergence scenario by strong statements from two scientific groups. These statements were not at first examined as critically as they should have been.

“We stand together to strongly condemn conspiracy theories suggesting that COVID-19 does not have a natural origin,” a group of virologists and others wrote in the Lancet on February 19, 2020, when it was really far too soon for anyone to be sure what had happened. Scientists “overwhelmingly conclude that this coronavirus originated in wildlife,” they said, with a stirring rallying call for readers to stand with Chinese colleagues on the frontline of fighting the disease.

Contrary to the letter writers’ assertion, the idea that the virus might have escaped from a lab invoked accident, not conspiracy. It surely needed to be explored, not rejected out of hand. A defining mark of good scientists is that they go to great pains to distinguish between what they know and what they don’t know. By this criterion, the signatories of the Lancet letter were behaving as poor scientists: they were assuring the public of facts they could not know for sure were true.

It later turned out that the Lancet letter had been organized and drafted by Peter Daszak, president of the EcoHealth Alliance of New York. Dr. Daszak’s organization funded coronavirus research at the Wuhan Institute of Virology. If the SARS2 virus had indeed escaped from research he funded, Dr. Daszak would be potentially culpable. This acute conflict of interest was not declared to the Lancet’s readers. To the contrary, the letter concluded, “We declare no competing interests.”

Peter Daszak, president of the EcoHealth Alliance

Virologists like Dr. Daszak had much at stake in the assigning of blame for the pandemic. For 20 years, mostly beneath the public’s attention, they had been playing a dangerous game. In their laboratories they routinely created viruses more dangerous than those that exist in nature. They argued they could do so safely, and that by getting ahead of nature they could predict and prevent natural “spillovers,” the cross-over of viruses from an animal host to people. If SARS2 had indeed escaped from such a laboratory experiment, a savage blowback could be expected, and the storm of public indignation would affect virologists everywhere, not just in China. “It would shatter the scientific edifice top to bottom,” an MIT Technology Review editor, Antonio Regalado, said in March 2020.

A second statement which had enormous influence in shaping public attitudes was a letter (in other words an opinion piece, not a scientific article) published on 17 March 2020 in the journal Nature Medicine. Its authors were a group of virologists led by Kristian G. Andersen of the Scripps Research Institute. “Our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus,” the five virologists declared in the second paragraph of their letter.

Kristian G. Andersen, Scripps Research

Unfortunately this was another case of poor science, in the sense defined above. True, some older methods of cutting and pasting viral genomes retain tell-tale signs of manipulation. But newer methods, called “no-see-um” or “seamless” approaches, leave no defining marks. Nor do other methods for manipulating viruses such as serial passage, the repeated transfer of viruses from one culture of cells to another. If a virus has been manipulated, whether with a seamless method or by serial passage, there is no way of knowing that this is the case. Dr. Andersen and his colleagues were assuring their readers of something they could not know.

The discussion part their letter begins, “It is improbable that SARS-CoV-2 emerged through laboratory manipulation of a related SARS-CoV-like coronavirus”. But wait, didn’t the lead say the virus had clearly not been manipulated? The authors’ degree of certainty seemed to slip several notches when it came to laying out their reasoning.

The reason for the slippage is clear once the technical language has been penetrated. The two reasons the authors give for supposing manipulation to be improbable are decidedly inconclusive.

First, they say that the spike protein of SARS2 binds very well to its target, the human ACE2 receptor, but does so in a different way from that which physical calculations suggest would be the best fit. Therefore the virus must have arisen by natural selection, not manipulation.

If this argument seems hard to grasp, it’s because it’s so strained. The authors’ basic assumption, not spelt out, is that anyone trying to make a bat virus bind to human cells could do so in only one way. First they would calculate the strongest possible fit between the human ACE2 receptor and the spike protein with which the virus latches onto it. They would then design the spike protein accordingly (by selecting the right string of amino acid units that compose it). But since the SARS2 spike protein is not of this calculated best design, the Andersen paper says, therefore it can’t have been manipulated.

But this ignores the way that virologists do in fact get spike proteins to bind to chosen targets, which is not by calculation but by splicing in spike protein genes from other viruses or by serial passage. With serial passage, each time the virus’s progeny are transferred to new cell cultures or animals, the more successful are selected until one emerges that makes a really tight bind to human cells. Natural selection has done all the heavy lifting. The Andersen paper’s speculation about designing a viral spike protein through calculation has no bearing on whether or not the virus was manipulated by one of the other two methods.

The authors’ second argument against manipulation is even more contrived. Although most living things use DNA as their hereditary material, a number of viruses use RNA, DNA’s close chemical cousin. But RNA is difficult to manipulate, so researchers working on coronaviruses, which are RNA-based, will first convert the RNA genome to DNA. They manipulate the DNA version, whether by adding or altering genes, and then arrange for the manipulated DNA genome to be converted back into infectious RNA.

Only a certain number of these DNA backbones have been described in the scientific literature. Anyone manipulating the SARS2 virus “would probably” have used one of these known backbones, the Andersen group writes, and since SARS2 is not derived from any of them, therefore it was not manipulated. But the argument is conspicuously inconclusive. DNA backbones are quite easy to make, so it’s obviously possible that SARS2 was manipulated using an unpublished DNA backbone.

And that’s it. These are the two arguments made by the Andersen group in support of their declaration that the SARS2 virus was clearly not manipulated. And this conclusion, grounded in nothing but two inconclusive speculations, convinced the world’s press that SARS2 could not have escaped from a lab. A technical critique of the Andersen letter takes it down in harsher words.

Science is supposedly a self-correcting community of experts who constantly check each other’s work. So why didn’t other virologists point out that the Andersen group’s argument was full of absurdly large holes? Perhaps because in today’s universities speech can be very costly. Careers can be destroyed for stepping out of line. Any virologist who challenges the community’s declared view risks having his next grant application turned down by the panel of fellow virologists that advises the government grant distribution agency.

The Daszak and Andersen letters were really political, not scientific statements, yet were amazingly effective. Articles in the mainstream press repeatedly stated that a consensus of experts had ruled lab escape out of the question or extremely unlikely. Their authors relied for the most part on the Daszak and Andersen letters, failing to understand the yawning gaps in their arguments. Mainstream newspapers all have science journalists on their staff, as do the major networks, and these specialist reporters are supposed to be able to question scientists and check their assertions. But the Daszak and Andersen assertions went largely unchallenged.

Doubts about natural emergence

Natural emergence was the media’s preferred theory until around February 2021 and the visit by a World Health Organization commission to China. The commission’s composition and access were heavily controlled by the Chinese authorities. Its members, who included the ubiquitous Dr. Daszak, kept asserting before, during and after their visit that lab escape was extremely unlikely. But this was not quite the propaganda victory the Chinese authorities may have been hoping for. What became clear was that the Chinese had no evidence to offer the commission in support of the natural emergence theory.

This was surprising because both the SARS1 and MERS viruses had left copious traces in the environment. The intermediary host species of SARS1 was identified within four months of the epidemic’s outbreak, and the host of MERS within nine months. Yet some 15 months after the SARS2 pandemic began, and a presumably intensive search, Chinese researchers had failed to find either the original bat population, or the intermediate species to which SARS2 might have jumped, or any serological evidence that any Chinese population, including that of Wuhan, had ever been exposed to the virus prior to December 2019. Natural emergence remained a conjecture which, however plausible to begin with, had gained not a shred of supporting evidence in over a year.

And as long as that remains the case, it’s logical to pay serious attention to the alternative conjecture, that SARS2 escaped from a lab.

Why would anyone want to create a novel virus capable of causing a pandemic? Ever since virologists gained the tools for manipulating a virus’s genes, they have argued they could get ahead of a potential pandemic by exploring how close a given animal virus might be to making the jump to humans. And that justified lab experiments in enhancing the ability of dangerous animal viruses to infect people, virologists asserted.

With this rationale, they have recreated the 1918 flu virus, shown how the almost extinct polio virus can be synthesized from its published DNA sequence, and introduced a smallpox gene into a related virus.

These enhancements of viral capabilities are known blandly as gain-of-function experiments. With coronaviruses, there was particular interest in the spike proteins, which jut out all around the spherical surface of the virus and pretty much determine which species of animal it will target. In 2000 Dutch researchers, for instance, earned the gratitude of rodents everywhere by genetically engineering the spike protein of a mouse coronavirus so that it would attack only cats.

Virologists started studying bat coronaviruses in earnest after these turned out to be the source of both the SARS1 and MERS epidemics. In particular, researchers wanted to understand what changes needed to occur in a bat virus’s spike proteins before it could infect people.

Researchers at the Wuhan Institute of Virology, led by China’s leading expert on bat viruses, Dr. Shi Zheng-li or “Bat Lady”, mounted frequent expeditions to the bat-infested caves of Yunnan in southern China and collected around a hundred different bat coronaviruses.

Dr. Shi then teamed up with Ralph S. Baric, an eminent coronavirus researcher at the University of North Carolina. Their work focused on enhancing the ability of bat viruses to attack humans so as to “examine the emergence potential (that is, the potential to infect humans) of circulating bat CoVs [coronaviruses].” In pursuit of this aim, in November 2015 they created a novel virus by taking the backbone of the SARS1 virus and replacing its spike protein with one from a bat virus (known as SHC014-CoV). This manufactured virus was able to infect the cells of the human airway, at least when tested against a lab culture of such cells.

The SHC014-CoV/SARS1 virus is known as a chimera because its genome contains genetic material from two strains of virus. If the SARS2 virus were to have been cooked up in Dr. Shi’s lab, then its direct prototype would have been the SHC014-CoV/SARS1 chimera, the potential danger of which concerned many observers and prompted intense discussion.

“If the virus escaped, nobody could predict the trajectory,” said Simon Wain-Hobson, a virologist at the Pasteur Institute in Paris.

Dr. Baric and Dr. Shi referred to the obvious risks in their paper but argued they should be weighed against the benefit of foreshadowing future spillovers. Scientific review panels, they wrote, “may deem similar studies building chimeric viruses based on circulating strains too risky to pursue.” Given various restrictions being placed on gain-of function (GOF) research, matters had arrived in their view at “a crossroads of GOF research concerns; the potential to prepare for and mitigate future outbreaks must be weighed against the risk of creating more dangerous pathogens. In developing policies moving forward, it is important to consider the value of the data generated by these studies and whether these types of chimeric virus studies warrant further investigation versus the inherent risks involved.”

That statement was made in 2015. From the hindsight of 2021, one can say that the value of gain-of-function studies in preventing the SARS2 epidemic was zero. The risk was catastrophic, if indeed the SARS2 virus was generated in a gain-of-function experiment.

Inside the Wuhan Institute of Virology

Dr. Baric had developed, and taught Dr. Shi, a general method for engineering bat coronaviruses to attack other species. The specific targets were human cells grown in cultures and humanized mice. These laboratory mice, a cheap and ethical stand-in for human subjects, are genetically engineered to carry the human version of a protein called ACE2 that studs the surface of cells that line the airways.

Dr. Shi returned to her lab at the Wuhan Institute of Virology and resumed the work she had started on genetically engineering coronaviruses to attack human cells.

Dr. Zheng-li Shi in a high safety (level BSL4) lab. Her coronavirus research was done in the much lower safety levels of BSL2 and BSL3 labs.

How can we be so sure?

Because, by a strange twist in the story, her work was funded by the National Institute of Allergy and Infectious Diseases (NIAID), a part of the U.S. National Institutes of Health (NIH). And grant proposals that funded her work, which are a matter of public record, specify exactly what she planned to do with the money.

The grants were assigned to the prime contractor, Dr. Daszak of the EcoHealth Alliance, who subcontracted them to Dr. Shi. Here are extracts from the grants for fiscal years 2018 and 2019. “CoV” stands for coronavirus and “S protein” refers to the virus’s spike protein.

“Test predictions of CoV inter-species transmission. Predictive models of host range (i.e. emergence potential) will be tested experimentally using reverse genetics, pseudovirus and receptor binding assays, and virus infection experiments across a range of cell cultures from different species and humanized mice.

“We will use S protein sequence data, infectious clone technology, in vitro and in vivo infection experiments and analysis of receptor binding to test the hypothesis that % divergence thresholds in S protein sequences predict spillover potential.”

What this means, in non-technical language, is that Dr. Shi set out to create novel coronaviruses with the highest possible infectivity for human cells. Her plan was to take genes that coded for spike proteins possessing a variety of measured affinities for human cells, ranging from high to low. She would insert these spike genes one by one into the backbone of a number of viral genomes (“reverse genetics” and “infectious clone technology”), creating a series of chimeric viruses. These chimeric viruses would then be tested for their ability to attack human cell cultures (“in vitro”) and humanized mice (“in vivo”). And this information would help predict the likelihood of “spillover,” the jump of a coronavirus from bats to people.

The methodical approach was designed to find the best combination of coronavirus backbone and spike protein for infecting human cells. The approach could have generated SARS2-like viruses, and indeed may have created the SARS2 virus itself with the right combination of virus backbone and spike protein.

It cannot yet be stated that Dr. Shi did or did not generate SARS2 in her lab because her records have been sealed, but it seems she was certainly on the right track to have done so. “It is clear that the Wuhan Institute of Virology was systematically constructing novel chimeric coronaviruses and was assessing their ability to infect human cells and human-ACE2-expressing mice,” says Richard H. Ebright, a molecular biologist at Rutgers University and leading expert on biosafety.

“It is also clear,” Dr. Ebright said, “that, depending on the constant genomic contexts chosen for analysis, this work could have produced SARS-CoV-2 or a proximal progenitor of SARS-CoV-2.” “Genomic context” refers to the particular viral backbone used as the testbed for the spike protein.

The lab escape scenario for the origin of the SARS2 virus, as should by now be evident, is not mere hand-waving in the direction of the Wuhan Institute of Virology. It is a detailed proposal, based on the specific project being funded there by the NIAID.

Even if the grant required the work plan described above, how can we be sure that the plan was in fact carried out? For that we can rely on the word of Dr. Daszak, who has been much protesting for the last 15 months that lab escape was a ludicrous conspiracy theory invented by China-bashers.

On 9 December 2019, before the outbreak of the pandemic became generally known, Dr. Daszak gave an interview in which he talked in glowing terms of how researchers at the Wuhan Institute of Virology had been reprogramming the spike protein and generating chimeric coronaviruses capable of infecting humanized mice.

“And we have now found, you know, after 6 or 7 years of doing this, over 100 new sars-related coronaviruses, very close to SARS,” Dr. Daszak says around minute 28 of the interview. “Some of them get into human cells in the lab, some of them can cause SARS disease in humanized mice models and are untreatable with therapeutic monoclonals and you can’t vaccinate against them with a vaccine. So, these are a clear and present danger….

“Interviewer: You say these are diverse coronaviruses and you can’t vaccinate against them, and no anti-virals — so what do we do?

“Daszak: Well I think…coronaviruses — you can manipulate them in the lab pretty easily. Spike protein drives a lot of what happen with coronavirus, in zoonotic risk. So you can get the sequence, you can build the protein, and we work a lot with Ralph Baric at UNC to do this. Insert into the backbone of another virus and do some work in the lab. So you can get more predictive when you find a sequence. You’ve got this diversity. Now the logical progression for vaccines is, if you are going to develop a vaccine for SARS, people are going to use pandemic SARS, but let’s insert some of these other things and get a better vaccine.” The insertions he referred to perhaps included an element called the furin cleavage site, discussed below, which greatly increases viral infectivity for human cells.

In disjointed style, Dr. Daszak is referring to the fact that once you have generated a novel coronavirus that can attack human cells, you can take the spike protein and make it the basis for a vaccine.

One can only imagine Dr. Daszak’s reaction when he heard of the outbreak of the epidemic in Wuhan a few days later. He would have known better than anyone the Wuhan Institute’s goal of making bat coronaviruses infectious to humans, as well as the weaknesses in the institute’s defense against their own researchers becoming infected.

But instead of providing public health authorities with the plentiful information at his disposal, he immediately launched a public relations campaign to persuade the world that the epidemic couldn’t possibly have been caused by one of the institute’s souped-up viruses. “The idea that this virus escaped from a lab is just pure baloney. It’s simply not true,” he declared in an April 2020 interview.

The Safety Arrangements at the Wuhan Institute of Virology

Dr. Daszak was possibly unaware of, or perhaps he knew all too well, the long history of viruses escaping from even the best run laboratories. The smallpox virus escaped three times from labs in England in the 1960’s and 1970’s, causing 80 cases and 3 deaths. Dangerous viruses have leaked out of labs almost every year since. Coming to more recent times, the SARS1 virus has proved a true escape artist, leaking from laboratories in Singapore, Taiwan, and no less than four times from the Chinese National Institute of Virology in Beijing.

One reason for SARS1 being so hard to handle is that there were no vaccines available to protect laboratory workers. As Dr. Daszak mentioned in his December 19 interview quoted above, the Wuhan researchers too had been unable to develop vaccines against the coronaviruses they had designed to infect human cells. They would have been as defenseless against the SARS2 virus, if it were generated in their lab, as their Beijing colleagues were against SARS1.

A second reason for the severe danger of novel coronaviruses has to do with the required levels of lab safety. There are four degrees of safety, designated BSL1 to BSL4, with BSL4 being the most restrictive and designed for deadly pathogens like the Ebola virus.

The Wuhan Institute of Virology had a new BSL4 lab, but its state of readiness considerably alarmed the State Department inspectors who visited it from the Beijing embassy in 2018. “The new lab has a serious shortage of appropriately trained technicians and investigators needed to safely operate this high-containment laboratory,” the inspectors wrote in a cable of 19 January 2018.

The real problem, however, was not the unsafe state of the Wuhan BSL4 lab but the fact that virologists worldwide don’t like working in BSL4 conditions. You have to wear a space suit, do operations in closed cabinets and accept that everything will take twice as long. So the rules assigning each kind of virus to a given safety level were laxer than some might think was prudent.

Before 2020, the rules followed by virologists in China and elsewhere required that experiments with the SARS1 and MERS viruses be conducted in BSL3 conditions. But all other bat coronaviruses could be studied in BSL2, the next level down. BSL2 requires taking fairly minimal safety precautions, such as wearing lab coats and gloves, not sucking up liquids in a pipette, and putting up biohazard warning signs. Yet a gain-of-function experiment conducted in BSL2 might produce an agent more infectious than either SARS1 or MERS. And if it did, then lab workers would stand a high chance of infection, especially if unvaccinated.

Much of Dr. Shi’s work on gain-of-function in coronaviruses was performed at the BSL2 safety level, as is stated in her publications and other documents. She has said in an interview with Science magazine that “The coronavirus research in our laboratory is conducted in BSL-2 or BSL-3 laboratories.”

“It is clear that some or all of this work was being performed using a biosafety standard — biosafety level 2, the biosafety level of a standard US dentist’s office — that would pose an unacceptably high risk of infection of laboratory staff upon contact with a virus having the transmission properties of SARS-CoV-2,” says Dr. Ebright.

“It also is clear,” he adds, “that this work never should have been funded and never should have been performed.”

This is a view he holds regardless of whether or not the SARS2 virus ever saw the inside of a lab.

Concern about safety conditions at the Wuhan lab was not, it seems, misplaced. According to a fact sheet issued by the State Department on January 15,2021, “ The U.S. government has reason to believe that several researchers inside the WIV became sick in autumn 2019, before the first identified case of the outbreak, with symptoms consistent with both COVID-19 and common seasonal illnesses.”

David Asher, a fellow of the Hudson Institute and former consultant to the State Department, provided more detail about the incident at a seminar. Knowledge of the incident came from a mix of public information and “some high end information collected by our intelligence community,” he said. Three people working at a BSL3 lab at the institute fell sick within a week of each other with severe symptoms that required hospitalization. This was “the first known cluster that we’re aware of, of victims of what we believe to be COVID-19.” Influenza could not completely be ruled out but seemed unlikely in the circumstances, he said.

Comparing the Rival Scenarios of SARS2 Origin

The evidence above adds up to a serious case that the SARS2 virus could have been created in a lab, from which it then escaped. But the case, however substantial, falls short of proof. Proof would consist of evidence from the Wuhan Institute of Virology, or related labs in Wuhan, that SARS2 or a predecessor virus was under development there. For lack of access to such records, another approach is to take certain salient facts about the SARS2 virus and ask how well each is explained by the two rival scenarios of origin, those of natural emergence and lab escape. Here are four tests of the two hypotheses. A couple have some technical detail, but these are among the most persuasive for those who may care to follow the argument.

1) The place of origin.

Start with geography. The two closest known relatives of the SARS2 virus were collected from bats living in caves in Yunnan, a province of southern China. If the SARS2 virus had first infected people living around the Yunnan caves, that would strongly support the idea that the virus had spilled over to people naturally. But this isn’t what happened. The pandemic broke out 1,500 kilometers away, in Wuhan.

Beta-coronaviruses, the family of bat viruses to which SARS2 belongs, infect the horseshoe bat Rhinolophus affinis, which ranges across southern China. The bats’ range is 50 kilometers, so it’s unlikely that any made it to Wuhan. In any case, the first cases of the Covid-19 pandemic probably occurred in September, when temperatures in Hubei province are already cold enough to send bats into hibernation.

What if the bat viruses infected some intermediate host first? You would need a longstanding population of bats in frequent proximity with an intermediate host, which in turn must often cross paths with people. All these exchanges of virus must take place somewhere outside Wuhan, a busy metropolis which so far as is known is not a natural habitat of Rhinolophusbat colonies. The infected person (or animal) carrying this highly transmissible virus must have traveled to Wuhan without infecting anyone else. No one in his or her family got sick. If the person jumped on a train to Wuhan, no fellow passengers fell ill.

It’s a stretch, in other words, to get the pandemic to break out naturally outside Wuhan and then, without leaving any trace, to make its first appearance there.

For the lab escape scenario, a Wuhan origin for the virus is a no-brainer. Wuhan is home to China’s leading center of coronavirus research where, as noted above, researchers were genetically engineering bat coronaviruses to attack human cells. They were doing so under the minimal safety conditions of a BSL2 lab. If a virus with the unexpected infectiousness of SARS2 had been generated there, its escape would be no surprise.

2) Natural history and evolution

The initial location of the pandemic is a small part of a larger problem, that of its natural history. Viruses don’t just make one time jumps from one species to another. The coronavirus spike protein, adapted to attack bat cells, needs repeated jumps to another species, most of which fail, before it gains a lucky mutation. Mutation — a change in one of its RNA units — causes a different amino acid unit to be incorporated into its spike protein and makes the spike protein better able to attack the cells of some other species.

Through several more such mutation-driven adjustments, the virus adapts to its new host, say some animal with which bats are in frequent contact. The whole process then resumes as the virus moves from this intermediate host to people.

In the case of SARS1, researchers have documented the successive changes in its spike protein as the virus evolved step by step into a dangerous pathogen. After it had gotten from bats into civets, there were six further changes in its spike protein before it became a mild pathogen in people. After a further 14 changes, the virus was much better adapted to humans, and with a further 4 the epidemic took off.

But when you look for the fingerprints of a similar transition in SARS2, a strange surprise awaits. The virus has changed hardly at all, at least until recently. From its very first appearance, it was well adapted to human cells. Researchers led by Alina Chan of the Broad Institute compared SARS2 with late stage SARS1, which by then was well adapted to human cells, and found that the two viruses were similarly well adapted. “By the time SARS-CoV-2 was first detected in late 2019, it was already pre-adapted to human transmission to an extent similar to late epidemic SARS-CoV,” they wrote.

Even those who think lab origin unlikely agree that SARS2 genomes are remarkably uniform. Dr. Baric writes that “early strains identified in Wuhan, China, showed limited genetic diversity, which suggests that the virus may have been introduced from a single source.”

A single source would of course be compatible with lab escape, less so with the massive variation and selection which is evolution’s hallmark way of doing business.

The uniform structure of SARS2 genomes gives no hint of any passage through an intermediate animal host, and no such host has been identified in nature.

Proponents of natural emergence suggest that SARS2 incubated in a yet-to-be found human population before gaining its special properties. Or that it jumped to a host animal outside China.

All these conjectures are possible, but strained. Proponents of lab leak have a simpler explanation. SARS2 was adapted to human cells from the start because it was grown in humanized mice or in lab cultures of human cells, just as described in Dr. Daszak’s grant proposal. Its genome shows little diversity because the hallmark of lab cultures is uniformity.

Proponents of laboratory escape joke that of course the SARS2 virus infected an intermediary host species before spreading to people, and that they have identified it — a humanized mouse from the Wuhan Institute of Virology.

3) The furin cleavage site.

The furin cleavage site is a minute part of the virus’s anatomy but one that exerts great influence on its infectivity. It sits in the middle of the SARS2 spike protein. It also lies at the heart of the puzzle of where the virus came from.

The spike protein has two sub-units with different roles. The first, called S1, recognizes the virus’s target, a protein called angiotensin converting enzyme-2 (or ACE2) which studs the surface of cells lining the human airways. The second, S2, helps the virus, once anchored to the cell, to fuse with the cell’s membrane. After the virus’s outer membrane has coalesced with that of the stricken cell, the viral genome is injected into the cell, hijacks its protein-making machinery and forces it to generate new viruses.

But this invasion cannot begin until the S1 and S2 subunits have been cut apart. And there, right at the S1/S2 junction, is the furin cleavage site that ensures the spike protein will be cleaved in exactly the right place.

The virus, a model of economic design, does not carry its own cleaver. It relies on the cell to do the cleaving for it. Human cells have a protein cutting tool on their surface known as furin. Furin will cut any protein chain that carries its signature target cutting site. This is the sequence of amino acid units proline-arginine-arginine-alanine, or PRRA in the code that refers to each amino acid by a letter of the alphabet. PRRA is the amino acid sequence at the core of SARS2’s furin cleavage site.

Viruses have all kinds of clever tricks, so why does the furin cleavage site stand out? Because of all known SARS-related beta-coronaviruses, only SARS2 possesses a furin cleavage site. All the other viruses have their S2 unit cleaved at a different site and by a different mechanism.

How then did SARS2 acquire its furin cleavage site? Either the site evolved naturally, or it was inserted by researchers at the S1/S2 junction in a gain-of-function experiment.

Consider natural origin first. Two ways viruses evolve are by mutation and by recombination. Mutation is the process of random change in DNA (or RNA for coronaviruses) that usually results in one amino acid in a protein chain being switched for another. Many of these changes harm the virus but natural selection retains the few that do something useful. Mutation is the process by which the SARS1 spike protein gradually switched its preferred target cells from those of bats to civets, and then to humans.

Mutation seems a less likely way for SARS2’s furin cleavage site to be generated, even though it can’t completely be ruled out. The site’s four amino acid units are all together, and all at just the right place in the S1/S2 junction. Mutation is a random process triggered by copying errors (when new viral genomes are being generated) or by chemical decay of genomic units. So it typically affects single amino acids at different spots in a protein chain. A string of amino acids like that of the furin cleavage site is much more likely to be acquired all together through a quite different process known as recombination.

Recombination is an inadvertent swapping of genomic material that occurs when two viruses happen to invade the same cell, and their progeny are assembled with bits and pieces of RNA belonging to the other. Beta-coronaviruses will only combine with other beta-coronaviruses but can acquire, by recombination, almost any genetic element present in the collective genomic pool. What they cannot acquire is an element the pool does not possess. And no known SARS-related beta-coronavirus, the class to which SARS2 belongs, possesses a furin cleavage site.

Proponents of natural emergence say SARS2 could have picked up the site from some as yet unknown beta-coronavirus. But bat SARS-related beta-coronaviruses evidently don’t need a furin cleavage site to infect bat cells, so there’s no great likelihood that any in fact possesses one, and indeed none has been found so far.

The proponents’ next argument is that SARS2 acquired its furin cleavage site from people. A predecessor of SARS2 could have been circulating in the human population for months or years until at some point it acquired a furin cleavage site from human cells. It would then have been ready to break out as a pandemic.

If this is what happened, there should be traces in hospital surveillance records of the people infected by the slowly evolving virus. But none has so far come to light. According to the WHO report on the origins of the virus, the sentinel hospitals in Hubei province, home of Wuhan, routinely monitor influenza-like illnesses and “no evidence to suggest substantial SARSCoV-2 transmission in the months preceding the outbreak in December was observed.”

So it’s hard to explain how the SARS2 virus picked up its furin cleavage site naturally, whether by mutation or recombination.

That leaves a gain-of-function experiment. For those who think SARS2 may have escaped from a lab, explaining the furin cleavage site is no problem at all. “Since 1992 the virology community has known that the one sure way to make a virus deadlier is to give it a furin cleavage site at the S1/S2 junction in the laboratory,” writes Dr. Steven Quay, a biotech entrepreneur interested in the origins of SARS2. “At least eleven gain-of-function experiments, adding a furin site to make a virus more infective, are published in the open literature, including [by] Dr. Zhengli Shi, head of coronavirus research at the Wuhan Institute of Virology.”

4) A Question of Codons

There’s another aspect of the furin cleavage site that narrows the path for a natural emergence origin even further.

As everyone knows (or may at least recall from high school), the genetic code uses three units of DNA to specify each amino acid unit of a protein chain. When read in groups of 3, the 4 different kinds of DNA unit can specify 4 x 4 x 4 or 64 different triplets, or codons as they are called. Since there are only 20 kinds of amino acid, there are more than enough codons to go around, allowing some amino acids to be specified by more than one codon. The amino acid arginine, for instance, can be designated by any of the six codons CGU, CGC, CGA, CGG, AGA or AGG, where A, U, G and C stand for the four different kinds of unit in RNA.

Here’s where it gets interesting. Different organisms have different codon preferences. Human cells like to designate arginine with the codons CGT, CGC or CGG. But CGG is coronavirus’s least popular codon for arginine. Keep that in mind when looking at how the amino acids in the furin cleavage site are encoded in the SARS2 genome.

Now the functional reason why SARS2 has a furin cleavage site, and its cousin viruses don’t, can be seen by lining up (in a computer) the string of nearly 30,000 nucleotides in its genome with those of its cousin coronaviruses, of which the closest so far known is one called RaTG13. Compared with RaTG13, SARS2 has a 12-nucleotide insert right at the S1/S2 junction. The insert is the sequence T-CCT-CGG-CGG-GC. The CCT codes for proline, the two CGG’s for two arginines, and the GC is the beginning of a GCA codon that codes for alanine.

There are several curious features about this insert but the oddest is that of the two side-by-side CGG codons. Only 5% of SARS2’s arginine codons are CGG, and the double codon CGG-CGG has not been found in any other beta-coronavirus. So how did SARS2 acquire a pair of arginine codons that are favored by human cells but not by coronaviruses?

Proponents of natural emergence have an up-hill task to explain all the features of SARS2’s furin cleavage site. They have to postulate a recombination event at a site on the virus’s genome where recombinations are rare, and the insertion of a 12-nucleotide sequence with a double arginine codon unknown in the beta-coronavirus repertoire, at the only site in the genome that would significantly expand the virus’s infectivity.

“Yes, but your wording makes this sound unlikely — viruses are specialists at unusual events,” is the riposte of David L. Robertson, a virologist at the University of Glasgow who regards lab escape as a conspiracy theory. “Recombination is naturally very, very frequent in these viruses, there are recombination breakpoints in the spike protein and these codons appear unusual exactly because we’ve not sampled enough.”

Dr. Robertson is correct that evolution is always producing results that may seem unlikely but in fact are not. Viruses can generate untold numbers of variants but we see only the one-in-a-billion that natural selection picks for survival. But this argument could be pushed too far. For instance any result of a gain-of-function experiment could be explained as one that evolution would have arrived at in time. And the numbers game can be played the other way. For the furin cleavage site to arise naturally in SARS2, a chain of events has to happen, each of which is quite unlikely for the reasons given above. A long chain with several improbable steps is unlikely to ever be completed.

For the lab escape scenario, the double CGG codon is no surprise. The human-preferred codon is routinely used in labs. So anyone who wanted to insert a furin cleavage site into the virus’s genome would synthesize the PRRA-making sequence in the lab and would be likely to use CGG codons to do so.

“When I first saw the furin cleavage site in the viral sequence, with its arginine codons, I said to my wife it was the smoking gun for the origin of the virus,” said David Baltimore, an eminent virologist and former president of CalTech. “These features make a powerful challenge to the idea of a natural origin for SARS2,” he said.

A Third Scenario of Origin

There’s a variation on the natural emergence scenario that’s worth considering. This is the idea that SARS2 jumped directly from bats to humans, without going through an intermediate host as SARS1 and MERS did. A leading advocate is the virologist David Robertson who notes that SARS2 can attack several other species besides humans. He believes the virus evolved a generalist capability while still in bats. Because the bats it infects are widely distributed in southern and central China, the virus had ample opportunity to jump to people, even though it seems to have done so on only one known occasion. Dr. Robertson’s thesis explains why no one has so far found a trace of SARS2 in any intermediate host or in human populations surveilled before December 2019. It would also explain the puzzling fact that SARS2 has not changed since it first appeared in humans — it didn’t need to because it could already attack human cells efficiently.

One problem with this idea, though, is that if SARS2 jumped from bats to people in a single leap and hasn’t changed much since, it should still be good at infecting bats. And it seems it isn’t.

“Tested bat species are poorly infected by SARS-CoV-2 and they are therefore unlikely to be the direct source for human infection,” write a scientific group skeptical of natural emergence.

Still, Dr. Robertson may be onto something. The bat coronaviruses of the Yunnan caves can infect people directly. In April 2012 six miners clearing bat guano from the Mojiang mine contracted severe pneumonia with Covid-19-like symptoms and three eventually died. A virus isolated from the Mojiang mine, called RaTG13, is still the closest known relative of SARS2. Much mystery surrounds the origin, reporting and strangely low affinity of RaTG13 for bat cells, as well as the nature of 8 similar viruses that Dr. Shi reports she collected at the same time but has not yet published despite their great relevance to the ancestry of SARS2. But all that is a story for another time. The point here is that bat viruses can infect people directly, though only in special conditions.

So who else, besides miners excavating bat guano, comes into particularly close contact with bat coronaviruses? Well, coronavirus researchers do. Dr. Shi says she and her group collected more than 1,300 bat samples during some 8 visits to the Mojiang cave between 2012 and 2015, and there were doubtless many expeditions to other Yunnan caves.

Imagine the researchers making frequent trips from Wuhan to Yunnan and back, stirring up bat guano in dark caves and mines, and now you begin to see a possible missing link between the two places. Researchers could have gotten infected during their collecting trips, or while working with the new viruses at the Wuhan Institute of Virology. The virus that escaped from the lab would have been a natural virus, not one cooked up by gain of function.

The direct-from-bats thesis is a chimera between the natural emergence and lab escape scenarios. It’s a possibility that can’t be dismissed. But against it are the facts that 1) both SARS2 and RaTG13 seem to have only feeble affinity for bat cells, so one can’t be fully confident that either ever saw the inside of a bat; and 2) the theory is no better than the natural emergence scenario at explaining how SARS2 gained its furin cleavage site, or why the furin cleavage site is determined by human-preferred arginine codons instead of by the bat-preferred codons.

Where We Are So Far

Neither the natural emergence nor the lab escape hypothesis can yet be ruled out. There is still no direct evidence for either. So no definitive conclusion can be reached.

That said, the available evidence leans more strongly in one direction than the other. Readers will form their own opinion. But it seems to me that proponents of lab escape can explain all the available facts about SARS2 considerably more easily than can those who favor natural emergence.

It’s documented that researchers at the Wuhan Institute of Virology were doing gain-of-function experiments designed to make coronaviruses infect human cells and humanized mice. This is exactly the kind of experiment from which a SARS2-like virus could have emerged. The researchers were not vaccinated against the viruses under study, and they were working in the minimal safety conditions of a BSL2 laboratory. So escape of a virus would not be at all surprising. In all of China, the pandemic broke out on the doorstep of the Wuhan institute. The virus was already well adapted to humans, as expected for a virus grown in humanized mice. It possessed an unusual enhancement, a furin cleavage site, which is not possessed by any other known SARS-related beta-coronavirus, and this site included a double arginine codon also unknown among beta-coronaviruses. What more evidence could you want, aside from the presently unobtainable lab records documenting SARS2’s creation?

Proponents of natural emergence have a rather harder story to tell. The plausibility of their case rests on a single surmise, the expected parallel between the emergence of SARS2 and that of SARS1 and MERS. But none of the evidence expected in support of such a parallel history has yet emerged. No one has found the bat population that was the source of SARS2, if indeed it ever infected bats. No intermediate host has presented itself, despite an intensive search by Chinese authorities that included the testing of 80,000 animals. There is no evidence of the virus making multiple independent jumps from its intermediate host to people, as both the SARS1 and MERS viruses did. There is no evidence from hospital surveillance records of the epidemic gathering strength in the population as the virus evolved. There is no explanation of why a natural epidemic should break out in Wuhan and nowhere else. There is no good explanation of how the virus acquired its furin cleavage site, which no other SARS-related beta-coronavirus possesses, nor why the site is composed of human-preferred codons. The natural emergence theory battles a bristling array of implausibilities.

The records of the Wuhan Institute of Virology certainly hold much relevant information. But Chinese authorities seem unlikely to release them given the substantial chance that they incriminate the regime in the creation of the pandemic. Absent the efforts of some courageous Chinese whistle-blower, we may already have at hand just about all of the relevant information we are likely to get for a while.

So it’s worth trying to assess responsibility for the pandemic, at least in a provisional way, because the paramount goal remains to prevent another one. Even those who aren’t persuaded that lab escape is the more likely origin of the SARS2 virus may see reason for concern about the present state of regulation governing gain-of-function research. There are two obvious levels of responsibility: the first, for allowing virologists to perform gain-of-function experiments, offering minimal gain and vast risk; the second, if indeed SARS2 was generated in a lab, for allowing the virus to escape and unleash a world-wide pandemic. Here are the players who seem most likely to deserve blame.

1. Chinese virologists

First and foremost, Chinese virologists are to blame for performing gain-of-function experiments in mostly BSL2-level safety conditions which were far too lax to contain a virus of unexpected infectiousness like SARS2. If the virus did indeed escape from their lab, they deserve the world’s censure for a foreseeable accident that has already caused the deaths of 3 million people.

True, Dr. Shi was trained by French virologists, worked closely with American virologists and was following international rules for the containment of coronaviruses. But she could and should have made her own assessment of the risks she was running. She and her colleagues bear the responsibility for their actions.

I have been using the Wuhan Institute of Virology as a shorthand for all virological activities in Wuhan. It’s possible that SARS2 was generated in some other Wuhan lab, perhaps in an attempt to make a vaccine that worked against all coronaviruses. But until the role of other Chinese virologists is clarified, Dr. Shi is the public face of Chinese work on coronaviruses, and provisionally she and her colleagues will stand first in line for opprobrium.

2. Chinese authorities

China’s central authorities did not generate SARS2 but they sure did their utmost to conceal the nature of the tragedy and China’s responsibility for it. They suppressed all records at the Wuhan Institute of Virology and closed down its virus databases. They released a trickle of information, much of which may have been outright false or designed to misdirect and mislead. They did their best to manipulate the WHO’s inquiry into the virus’s origins, and led the commission’s members on a fruitless run-around. So far they have proved far more interested in deflecting blame than in taking the steps necessary to prevent a second pandemic.

3. The worldwide community of virologists

Virologists around the world are a loose-knit professional community. They write articles in the same journals. They attend the same conferences. They have common interests in seeking funds from governments and in not being overburdened with safety regulations.

Virologists knew better than anyone the dangers of gain-of-function research. But the power to create new viruses, and the research funding obtainable by doing so, was too tempting. They pushed ahead with gain-of-function experiments. They lobbied against the moratorium imposed on Federal funding for gain-of-function research in 2014 and it was raised in 2017.

The benefits of the research in preventing future epidemics have so far been nil, the risks vast. If research on the SARS1 and MERS viruses could only be done at the BSL3 safety level, it was surely illogical to allow any work with novel coronaviruses at the lesser level of BSL2. Whether or not SARS2 escaped from a lab, virologists around the world have been playing with fire.

Their behavior has long alarmed other biologists. In 2014 scientists calling themselves the Cambridge Working Group urged caution on creating new viruses. In prescient words, they specified the risk of creating a SARS2-like virus. “Accident risks with newly created ‘potential pandemic pathogens’ raise grave new concerns,” they wrote. “Laboratory creation of highly transmissible, novel strains of dangerous viruses, especially but not limited to influenza, poses substantially increased risks. An accidental infection in such a setting could trigger outbreaks that would be difficult or impossible to control.”

When molecular biologists discovered a technique for moving genes from one organism to another, they held a public conference at Asilomar in 1975 to discuss the possible risks. Despite much internal opposition, they drew up a list of stringent safety measures that could be relaxed in future — and duly were — when the possible hazards had been better assessed.

When the CRISPR technique for editing genes was invented, biologists convened a joint report by the U.S., UK and Chinese national academies of science to urge restraint on making heritable changes to the human genome. Biologists who invented gene drives have also been open about the dangers of their work and have sought to involve the public.

You might think the SARS2 pandemic would spur virologists to re-evaluate the benefits of gain-of-function research, even to engage the public in their deliberations. But no. Many virologists deride lab escape as a conspiracy theory and others say nothing. They have barricaded themselves behind a Chinese wall of silence which so far is working well to allay, or at least postpone, journalists’ curiosity and the public’s wrath. Professions that cannot regulate themselves deserve to get regulated by others, and this would seem to be the future that virologists are choosing for themselves.

4. The US Role in Funding the Wuhan Institute of Virology

From June 2014 to May 2019 Dr. Daszak’s EcoHealth Alliance had a grantfrom the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, to do gain-of-function research with coronaviruses at the Wuhan Institute of Virology. Whether or not SARS2 is the product of that research, it seems a questionable policy to farm out high-risk research to unsafe foreign labs using minimal safety precautions. And if the SARS2 virus did indeed escape from the Wuhan institute, then the NIH will find itself in the terrible position of having funded a disastrous experiment that led to death of more than 3 million worldwide, including more than half a million of its own citizens.

The responsibility of the NIAID and NIH is even more acute because for the first three years of the grant to EcoHealth Alliance there was a moratorium on funding gain-of-function research. Why didn’t the two agencies therefore halt the Federal funding as apparently required to do so by law? Because someone wrote a loophole into the moratorium.

The moratorium specifically barred funding any gain-of-function research that increased the pathogenicity of the flu, MERS or SARS viruses. But then a footnote on p.2 of the moratorium document states that “An exception from the research pause may be obtained if the head of the USG funding agency determines that the research is urgently necessary to protect the public health or national security.”

This seems to mean that either the director of the NIAID, Dr. Anthony Fauci, or the director of the NIH, Dr. Francis Collins, or maybe both, would have invoked the footnote in order to keep the money flowing to Dr. Shi’s gain-of-function research.

“Unfortunately, the NIAID Director and the NIH Director exploited this loophole to issue exemptions to projects subject to the Pause –preposterously asserting the exempted research was ‘urgently necessary to protect public health or national security’ — thereby nullifying the Pause,” Dr. Richard Ebright said in an interview with Independent Science News.

When the moratorium was ended in 2017 it didn’t just vanish but was replaced by a reporting system, the Potential Pandemic Pathogens Control and Oversight (P3CO) Framework, which required agencies to report for review any dangerous gain-of-function work they wished to fund.

According to Dr. Ebright, both Dr. Collins and Dr. Fauci “have declined to flag and forward proposals for risk-benefit review, thereby nullifying the P3CO Framework.”

In his view, the two officials, in dealing with the moratorium and the ensuing reporting system, “have systematically thwarted efforts by the White House, the Congress, scientists, and science policy specialists to regulate GoF [gain-of-function] research of concern.”

Possibly the two officials had to take into account matters not evident in the public record, such as issues of national security. Perhaps funding the Wuhan Institute of Virology, which is believed to have ties with Chinese military virologists, provided a window into Chinese biowarfare research. But whatever other considerations may have been involved, the bottom line is that the National Institutes of Health was supporting gain-of-function research, of a kind that could have generated the SARS2 virus, in an unsupervised foreign lab that was doing work in BSL2 biosafety conditions. The prudence of this decision can be questioned, whether or not SARS2 and the death of 3 million people was the result of it.

In Conclusion

If the case that SARS2 originated in a lab is so substantial, why isn’t this more widely known? As may now be obvious, there are many people who have reason not to talk about it. The list is led, of course, by the Chinese authorities. But virologists in the United States and Europe have no great interest in igniting a public debate about the gain-of-function experiments that their community has been pursuing for years.

Nor have other scientists stepped forward to raise the issue. Government research funds are distributed on the advice of committees of scientific experts drawn from universities. Anyone who rocks the boat by raising awkward political issues runs the risk that their grant will not be renewed and their research career will be ended. Maybe good behavior is rewarded with the many perks that slosh around the distribution system. And if you thought that Dr. Andersen and Dr. Daszak might have blotted their reputation for scientific objectivity after their partisan attacks on the lab escape scenario, look at the 2nd and 3rd names on this list of recipients of an $82 million grant announced by the National Institute of Allergy and Infectious Diseases in August 2020.

The US government shares a strange common interest with the Chinese authorities: neither is keen on drawing attention to the fact that Dr. Shi’s coronavirus work was funded by the US National Institutes of Health. One can imagine the behind-the-scenes conversation in which the Chinese government says “If this research was so dangerous, why did you fund it, and on our territory too?” To which the US side might reply, “Looks like it was you who let it escape. But do we really need to have this discussion in public?”

Dr. Fauci is a longtime public servant who served with integrity under President Trump and has resumed leadership in the Biden Administration in handling the Covid epidemic. Congress, no doubt understandably, may have little appetite for hauling him over the coals for the apparent lapse of judgment in funding gain-of-function research in Wuhan.

To these serried walls of silence must be added that of the mainstream media. To my knowledge, no major newspaper or television network has yet provided readers with an in-depth news story of the lab escape scenario, such as the one you have just read, although some have run brief editorials or opinion pieces. One might think that any plausible origin of a virus that has killed three million people would merit a serious investigation. Or that the wisdom of continuing gain-of-function research, regardless of the virus’s origin, would be worth some probing. Or that the funding of gain-of-function research by the NIH and NIAID during a moratorium on such funding would bear investigation. What accounts for the media’s apparent lack of curiosity?

The virologists’ omertà is one reason. Science reporters, unlike political reporters, have little innate skepticism of their sources’ motives; most see their role largely as purveying the wisdom of scientists to the unwashed masses. So when their sources won’t help, these journalists are at a loss.

Another reason, perhaps, is the migration of much of the media toward the left of the political spectrum. Because President Trump said the virus had escaped from a Wuhan lab, editors gave the idea little credence. They joined the virologists in regarding lab escape as a dismissible conspiracy theory. During the Trump Administration, they had no trouble in rejecting the position of the intelligence services that lab escape could not be ruled out. But when Avril Haines, President Biden’s director of National Intelligence, said the same thing, she too was largely ignored. This is not to argue that editors should have endorsed the lab escape scenario, merely that they should have explored the possibility fully and fairly.

People round the world who have been pretty much confined to their homes for the last year might like a better answer than their media are giving them. Perhaps one will emerge in time. After all, the more months pass without the natural emergence theory gaining a shred of supporting evidence, the less plausible it may seem. Perhaps the international community of virologists will come to be seen as a false and self-interested guide. The common sense perception that a pandemic breaking out in Wuhan might have something to do with a Wuhan lab cooking up novel viruses of maximal danger in unsafe conditions could eventually displace the ideological insistence that whatever Trump said can’t be true.

And then let the reckoning begin.

Nicholas Wade

April 30,2021


The first person to take a serious look at the origins of the SARS2 virus was Yuri Deigin, a biotech entrepreneur in Russia and Canada. In a long and brilliant essay, he dissected the molecular biology of the SARS2 virus and raised, without endorsing, the possibility that it had been manipulated. The essay, published on April 22, 2020, provided a roadmap for anyone seeking to understand the virus’s origins. Deigin packed so much information and analysis into his essay that some have doubted it could be the work of a single individual and suggested some intelligence agency must have authored it. But the essay is written with greater lightness and humor than I suspect are ever found in CIA or KGB reports, and I see no reason to doubt that Dr. Deigin is its very capable sole author.

In Deigin’s wake have followed several other skeptics of the virologists’ orthodoxy. Nikolai Petrovsky calculated how tightly the SARS2 virus binds to the ACE2 receptors of various species and found to his surprise that it seemed optimized for the human receptor, leading him to infer the virus might have been generated in a laboratory. Alina Chan published a papershowing that SARS2 from its first appearance was very well adapted to human cells.

One of the very few establishment scientists to have questioned the virologists’ absolute rejection of lab escape is Richard Ebright, who has long warned against the dangers of gain-of-function research. Another is David A. Relman of Stanford University. “Even though strong opinions abound, none of these scenarios can be confidently ruled in or ruled out with currently available facts,” he wrote. Kudos too to Robert Redfield, former director of the Centers for Disease Control and Prevention, who told CNNon March 26, 2021 that the “most likely” cause of the epidemic was “from a laboratory,” because he doubted that a bat virus could become an extreme human pathogen overnight, without taking time to evolve, as seemed to be the case with SARS2.

Steven Quay, a physician-researcher, has applied statistical and bioinformatic tools to ingenious explorations of the virus’s origin, showing for instance how the hospitals receiving the early patients are clustered along the Wuhan №2 subway line which connects the Institute of Virology at one end with the international airport at the other, the perfect conveyor belt for distributing the virus from lab to globe.

In June 2020 Milton Leitenberg published an early survey of the evidence favoring lab escape from gain-of-function research at the Wuhan Institute of Virology.

Many others have contributed significant pieces of the puzzle. “Truth is the daughter,” said Francis Bacon, “not of authority but time.” The efforts of people such as those named above are what makes it so.



Nicholas Wade is a science writer and has worked on the staff of Nature, Science and, for many years, on the New York Times.


MUST WATCH (click to learn about the U.S. patent on coronavirus)



George Webb - Investigative Journalist



By SotN - 16. June 2021

Screenshot of preceding tweet captured for posterity’s sake


Smoking gun: Wuhan collaborator Peter Daszak admits to developing “killer” coronaviruses with communist Chinese

Image: Smoking gun: Wuhan collaborator Peter Daszak admits to developing “killer” coronaviruses with communist ChineseBy:  - 09. June 2021

We now know that Peter Daszak of EcoHealth Alliance, who funneled millions of dollars to the Wuhan Institute of Virology that carried out gain-of-function weaponization experiments, bragged about his Chinese colleagues (whom he helped fund) creating “killer” coronaviruses.

A video unearthed by The National Pulse and widely circulated yesterday shows Daszak boasting about his research:

Then when you get a sequence of a virus, and it looks like a relative of a known nasty pathogen, just like we did with SARS. We found other coronaviruses in bats, a whole host of them, some of them looked very similar to SARS. So we sequenced the spike protein: the protein that attaches to cells. Then we… Well I didn’t do this work, but my colleagues in China did the work. You create pseudo particles, you insert the spike proteins from those viruses, see if they bind to human cells. At each step of this you move closer and closer to this virus could really become pathogenic in people… You end up with a small number of viruses that really do look like killers.

Daszak was essentially describing the weaponization of the SARS-CoV-2 spike protein that is now known to cause vascular damage, blood clots, strokes and other tissue damage while attacking the ovaries, testes, adrenal glands and neurological tissue.

Here’s the video of Daszak:


Fauci, Daszak, Baric and the international conspiracy to build biological weapons with the communist Chinese military

As more videos and emails continue to emerge, they describe a global money laundering operation and apparent criminal conspiracy to evade U.S. laws that prohibit gain-of-function research by funneling NIH money to communist China where the CCP military oversaw the weaponization experiments.

Whether deliberate or not, this weaponized virus escaped the Wuhan laboratory and proceeded to devastate the world due to the toxicity of its spike protein nanoparticle “payload.” While the virus replication engine itself appears to be nearly harmless, the spike protein payload is toxic and deadly, and that’s the nanoparticle that’s being placed into covid vaccines.

Thus, what Peter Daszak is essentially admitting to is an international conspiracy to hand communist China the funding and know-how to create weaponized nanoparticles (the spike protein) that are then placed into so-called “vaccines” and injected into people across America and around the world, potentially leading to global depopulation and infertility.

Dr. Byram Bridle is one doctor among many who are sounding the alarm about this spike protein as new bio-distribution studies show it circulates through the entire body, attacking the brain, heart, adrenal glands, spleen, large intestine, liver, ovaries and testes, among other organs:

Fauci and Daszak appear to have helped communist China build a biological weapon to decimate the West in a global biowarfare attack that may have already been unleashed

It is no coincidence that communist China has long sought to develop coronavirus bioweapons to attack the West. As reported by LifeSiteNews:

Documents Reveal Chinese Scientists Discussed Weaponising Coronavirus 5 Years Before Pandemic

Titled ‘The Unnatural Origin of SARS and New Species of Man-Made Viruses as Genetic Bioweapons’, the paper is said to have suggested that the third world war would be fought with biological weapons, revealing how Chinese scientists were discussing the weaponisation of SARS coronaviruses five years before the COVID-19 pandemic hit.

The executive director of the Australian Strategic Policy Institute (ASPI), Peter Jennings, said the document is as close to a “smoking gun as we’ve got”. “I think this is significant because it clearly shows that Chinese scientists were thinking about military application for different strains of the coronavirus and thinking about how it could be deployed,” Jennings was quoted as saying by news.com.au.

And then, from the UK Daily Mail:

China was preparing for a Third World War with biological weapons – including coronavirus – SIX years ago, according to dossier produced by the People’s Liberation Army in 2015 and uncovered by the US State Department

  • Beijing has considered the military potential of SARS coronaviruses since 2015
  • The bombshell document was accessed by US State Department investigators
  • Scientists examined manipulation of diseases ‘in a way never seen before’
  • Foreign affairs committee’s Tom Tugendhat says evidence is a ‘major concern’

It now appears that Fauci and Daszak helped with the funding and virology support of China’s effort to build a biological weapon that could be deployed against America and the West.

All those who promote covid vaccines are, in essence, working to help communist China carry out its attack against the West by promoting the injection of Americans with spike protein bioweapons developed by communist Chinese military bioweapons researchers.

The vaccine contains the biological weapon that was developed in China, in other words.


WATCH: Explosive, Unearthed Video Shows Peter Daszak Describing ‘Chinese Colleagues’ Developing ‘Killer’ Coronaviruses

By NATALIE WINTERS - 08. June 2021

EcoHealth Alliance President Peter Daszak – who collaborated with the Wuhan Institute of Virology on research funded by Dr. Anthony Fauci’s National Institute of Allergy and Infectious Disease – appears to boast about the manipulation of “killer” SARS-like coronaviruses carried out by his “colleagues in China” in a clip unearthed by The National Pulse.

Daszak made the admission at a 2016 forum discussing “emerging infectious diseases and the next pandemic,” which appears to be at odds with Fauci’s repeated denial of funding gain-of-function research at the Wuhan Institute of Virology.

While describing how his organization sequences deadly viruses, Daszak describes the process of “insert[ing] spike proteins” into viruses to see if they can “bind to human cells” as being carried out by his “colleagues in China”:

“Then when you get a sequence of a virus, and it looks like a relative of a known nasty pathogen, just like we did with SARS. We found other coronaviruses in bats, a whole host of them, some of them looked very similar to SARS. So we sequenced the spike protein: the protein that attaches to cells. Then we… Well I didn’t do this work, but my colleagues in China did the work. You create pseudo particles, you insert the spike proteins from those viruses, see if they bind to human cells. At each step of this you move closer and closer to this virus could really become pathogenic in people. 

“You end up with a small number of viruses that really do look like killers,” he adds.

The comments follow growing evidence that Fauci’s NIAID has deep financial and personnel ties to the Wuhan Institute of Virology – and that Daszak’s EcoHealth alliance was one of the primary proxies funneling the money to the Chinese Communist Party lab.

Over a dozen research papers carried out under a $3.7 million National Institute of Allergy and Infectious Disease (NIAID) grant list the Wuhan Lab’s Center for Emerging Infectious Diseases Director Shi Zhengli as a co-author alongside Daszak. Shi has included these Fauci-backed grants on her resume.

The Wuhan lab has also listed the National Institutes of Health (NIH) as one of its “partners,” secretly erasing the mention in March 2021.


 is an Investigative Reporter at the National Pulse and contributor to The National Pulse podcast.


Unearthed Evidence Shows Fauci Defended ‘Integral’ Gain-Of-Function Research Despite Pandemic ‘Risks’.


Dr. Fauci Attacked Trump for Lab Leak Theory Despite Not Having Access to the Intelligence

By KASH'S CORNER - 04. June 2021


(Ed.: The interview in itself it is a good example of what is wrong with USAmerican ways how to handle such crisis situations: It's all "show" - which of course must go on - without any moral competence nor moral compass to guide, but the task to disguise in typical conman fashion. Like here, most are just crisis actors and not crisis managers aong the administration as well as journalism. Alas, such doesn't bring the truth a jota more to the forefront nor humanity a single step ahead.)

When former President Donald Trump and others floated the Wuhan lab leak theory last year, they were blasted for pushing a “conspiracy theory.” Now fact-checkers are rescinding posts, and media outlets are quietly updating articles.

What is the Chinese Communist Party trying to cover up? And what did Dr. Anthony Fauci know at the time?

In this episode of Kash’s Corner, Kash Patel and Jan Jekielek sit down to discuss the growing questions surrounding the Wuhan Institute of Virology.

What role did the media and Big Tech play in all of this? And what is the significance of Florida’s new bill to counter Big Tech censorship?

Follow Jan on Twitter: @JanJekielek


Smoking gun: Communist China plans to fight WWIII with bioweapons

By  - 31. May 2021

Image: Smoking gun: Communist China plans to fight WWIII with bioweapons

The mainstream media has made a sudden about-face concerning the origin of the Wuhan coronavirus (Covid-19) by now suggesting that it may, after all, have come from a laboratory in China. New evidence has also emerged to suggest that China intentionally released the virus, rather than it having just been an “accident,” in order to unleash World War III.

Anthony Fauci’s secret “gain of function” research at the Wuhan Institute of Virology (WIV) is what many now believe ultimately led to the creation of the Chinese Virus, which following its release has been used to usher in communism on a global scale. It also appears as though Fauci was seditiously conspiring with the Chinese military, which has long desired deadly coronavirus bioweapons in order to attack the United States, India and other enemies.

For a while, it was completely off limits to talk about Fauci’s gain of function research, the WIV, or any other links tying the Chinese Virus to communist China. Now, the media is shifting narratives in what appears to be an effort to build a case for the possibility of impending war with the Chicoms.

“It doesn’t require much in the way of a leap of the imagination to anticipate that the same murderous regime that has brought us forced abortion and sterilization, forced organ harvesting, and genocide in real time would also be developing deadly bioweapons to release upon the world,” writes Steven Mosher for LifeSiteNews.

“And we now know that China’s military strategists were planning to do just that.”

Is the CCP trying to wage a third world war against its enemies?

The Australian Strategic Policy Institute (ASPI) is credited with uncovering a Chinese book that claims Chinese military scientists have been working on developing a “new era of genetic weapons” that could be “artificially manipulated into an emerging human disease virus, then weaponized and unleashed.”

Entitled The Unnatural Origin of SARS and New Species of Man-Made Viruses as Genetic Bioweapons, the 2015 volume make reference to WWIII and these novel bioweapons being used to fight it. Could it be that we are now seeing the early stages of that with the Wuhan Flu?

Even more interesting are the direct references to modified coronaviruses, which the Chinese military views as being easy to weaponize. Chinese scientists had actually referenced SARS, a “cousin” of the Chinese Virus, as the ideal candidate for a bioweapon.

The World Health Organization (WHO) and other globalist entities have referred to the Wuhan coronavirus (Covid-19) as a “type of SARS virus,” which further builds the case. ASPI executive director Peter Jennings calls the findings the closest thing to a “smoking gun as we’ve got.”

“I think this is significant because it clearly shows that Chinese scientists were thinking about military application for different strains of the coronavirus and thinking about how it could be deployed,” Jennings is further quoted as saying.

“It begins to firm up the possibility that what we have here [in the China Virus] is the accidental release of a pathogen for military use.”

This would explain why the Chinese Communist Party (CCP) is resisting all outside investigation into the Wuhan Flu’s true origins, instead choosing to push the long-debunked narrative that it came from tainted bats at a local wet market.

“If this was a case of transmission from a wet market it would be in China’s interest to co-operate,” Jennings says. “We’ve had the opposite of that.”

To this day, the CCP has done nothing but obstruct all efforts by foreign entities to dig deeper into the origins of the Chinese Virus. Could it be that the communist regime is covering for trying to unleash WWIII?


Sources for this article include:




China virus ‘smoking gun’ found

Chinese scientists discussed fighting WWIII with bioweapons—including coronaviruses

Featured Image

I have long believed – based on a lifelong study of Communist China and my background in biology – that the China Virus was a laboratory construct.  

At best, as I wrote in the New York Post on February 22 of last year, it was the result of a reckless “Gain of Function” experiment that created a highly contagious pathogen that somehow escaped from the lab.  

At worst, it was a deliberate attempt by the Chinese military to genetically engineer a bioweapon that could be used to attack China’s enemies, chiefly the United States and India.

Until recently, merely hinting at either possibility was enough to get you banned from social media and dismissed by the mainstream media as a paranoid crank. In fact, that’s exactly what Facebook did, quickly suppressing my column as “False Information.”  

It took a couple of months to convince the 20-something “fact checkers” who work there that there was more to the story of the Wuhan Flu than someone getting a bad bowl of bat soup. After all, there were scientific publications proving that China was engaged in dangerous “Gain of Function” research along with evidence that it had an active bioweapons program.   

As the old joke goes, it’s not paranoia if they’re really out to get you. And, as I have described at length in my book, Bully of Asia, the Chinese Communist Party really is out to get us.   

It doesn’t require much in the way of a leap of the imagination to anticipate that the same murderous regime that has brought us forced abortion and sterilization, forced organ harvesting, and genocide in real time would also be developing deadly bioweapons to release upon the world.  

And we now know that China’s military strategists were planning to do just that.  

The Australian Strategic Policy Institute (ASPI) has just uncovered a Chinese book that proves that Chinese military scientists have been working towards the development of a “new era of genetic weapons.” These weapons, the Chinese scientists promised, could be “artificially manipulated into an emerging human disease virus, then weaponized and unleashed.”

In the 2015 volume, called The Unnatural Origin of SARS and New Species of Man-Made Viruses as Genetic Bioweapons, the Chinese military scientists begin by suggesting that World War III would be fought with biological weapons. 

And not just any bioweapons.  

Coronaviruses, a number of which cause respiratory illnesses in people, were mentioned as a class of viruses that could be readily weaponized. Indeed, the Chinese scientists were even more explicit, pointing out in their paper that the coronavirus that causes Severe Acute Respiratory Syndrome, or SARS, was an ideal candidate for a bioweapon. 

I do not think that it is any accident that the China Virus – or COVID-19 as the World Health Organization insists that we call it – is a type of SARS virus.  

Now you understand why Peter Jennings, the executive director of the Australian Strategic Policy Institute (ASPI), described the new document as the closest thing to a “smoking gun as we’ve got.”  

News.com.au quoted Jennings as saying that “I think this is significant because it clearly shows that Chinese scientists were thinking about military application for different strains of the coronavirus and thinking about how it could be deployed. It begins to firm up the possibility that what we have here [in the China Virus] is the accidental release of a pathogen for military use.”

Jennings also believes, as I do, that the China Virus’s origins as a bioweapon explain why China has blocked investigations. “If this was a case of transmission from a wet market it would be in China’s interest to co-operate,” Jennings pointed out. “We’ve had the opposite of that.”

Indeed, we’ve had a full-blown cover up, which continues to the present day. As former Deputy National Security Advisor (DNSA) Mathew Pottinger pointed out in a February interview., U.S. intelligence believed that the Chinese People’s Liberation Army (PLA) had been “doing secret classified animal experiments in that same laboratory [Wuhan Institute of Virology]” as early as 2017. He added that there is “good reason to believe” that an outbreak of a “flu-like illness” had occurred among the scientists in the Wuhan Institute of Virology (WIV) in the fall of 2019, just before the first cases of a new type of pneumonia were being reported in Wuhan.

While the Wuhan lab poses as a “civilian institution,” Pottinger said, U.S. intelligence has determined that the lab has collaborated on publications and secret bioweapons projects with China’s military. 

Pottinger also noted, as I did in my February 2020 article, one final – and very telling – point: when the outbreak in Wuhan began it was the Chinese military, and not the Chinese CDC, that was called in to handle the situation.

This is exactly what you would expect to happen if the China Virus was a product of a military bioweapons program.

No one currently serving in the Biden administration has been willing to go quite this far. But even they have begun to backtrack from the bat soup story of late.   Biden’s Director of National Intelligence, Avril Haines, recently admitted that one of the two possible explanations for the origin of COVID-19 would involve an “escape” from a Chinese bio lab in Wuhan. 

Former Secretary of State Mike Pompeo said that, where the CCP is concerned, America should “distrust and verify.”  

China’s official explanation is clearly a fabrication.  

More and more evidence suggests that the China Virus was indeed a bioweapon that was deliberately released upon the world. 


Steven W. Mosher is the president of the Population Research Institute and the author of Bully of Asia: Why China’s Dream is the New Threat to World Order.


U.S. Dem Committee Chair Calls For COVID Origins Investigation Considering ‘Every Hypothesis Available.’

By NATALIE WINTERS - 16. May 2021

Democratic Congresswoman Anna Eshoo called for an investigation into the origins of COVID-19 that considers “every hypothesis available.”


The Chairwoman of the Energy and Commerce Health Subcommittee released the following statement in response to a recent statement from 18 researchers published in the journal Science that encouraged others to take theories about “laboratory spillovers seriously.”

In full, Rep. Eshoo’s statement reads:

“I applaud Stanford University’s Dr. David Relman and 17 other esteemed scientists on their open letter published in Science calling for a transparent, objective, and data-driven investigation into the origins of COVID-19. In order to crush the virus and prevent future global pandemics, we must consider every hypothesis available and have non-partisan, independent, scientific experts conduct an investigation to inform our understanding of COVID-19 and similar infectious diseases. I stand ready to support the Biden Administration and our international partners in such an investigation of COVID-19 and SARS-CoV-2 origins, and I’m grateful to the scientists for leading this effort.”

Among the signatories of the Science letter are professors from institutions including Harvard, Stanford, and Yale. Dr. Ralph Baric – whose gain-of-function research record and ties to the Wuhan Institute of Virology were recently discussed in an exchange between Dr. Anthony Fauci and Senator Rand Paul – also signed the letter.

The letter also comes one day after The National Pulse unearthed a conference focused on gain-of-function research at the Wuhan Institute of Virology with several National Institute of Allergy and Infectious Diseases (NIAID)-funded researchers in attendance. Among them was Dr. David Relman – the organizer of the letter.

 - is an Investigative Reporter at the National Pulse and contributor to The National Pulse podcast.


"The Canadian Connection" with Special Guest, David Hawkins, and host, Jason Goodman

•Streamed live on 15 May 2021

John E Hoover

This analysis is not news. This video is an independent opinion journalism project and represents our opinion, and our opinion only.


THIS VIDEO MAY CONTAIN COPYRIGHTED MATERIAL. SUCH MATERIAL IS MADE AVAILABLE FOR EDUCATIONAL PURPOSES ONLY. THIS CONSTITUTES A 'FAIR USE' OF ANY SUCH MATERIAL AS PROVIDED FOR PURSUANT TO TITLE 17 UNITED STATES CODE SECTION 106A-117 REGARDING USE OF COPYRIGHT MATERIAL. FURTHER, ONLY SMALL PORTIONS OF EACH LISTED CREDIT ARE USED. THIS CREATOR THANKS EACH PERSONALLY IN ADVANCE. FAIR USE NOTICE: Copyright Disclaimer Under Section 107 of the Copyright Act 1976, allowance is made for "fair use" for purposes such as criticism, comment, news reporting, teaching, scholarship, and research. Fair use is a use permitted by copyright statute that might otherwise be infringing. Non-profit, educational or personal use tips the balance in favor of fair use. This effort here is respectfully submitted and credit is listed below. Only small portions of each listed has been used and/or we have requested permission to use in advance. Upon request verification can be submitted.



 2020 Nov 17 : 2000240.

doi: 10.1002/bies.202000240 [Epub ahead of print]

PMCID: PMC7744920

PMID: 33200842

The genetic structure of SARS‐CoV‐2 does not rule out a laboratory origin

SARS‐COV‐2 chimeric structure and furin cleavage site might be the result of genetic manipulation

Rossana Segretocorresponding author 1 and Yuri Deigin 2

Author information Article notes Copyright and License information Disclaimer

This article has been cited by other articles in PMC.

Associated Data

Data Availability Statement


Severe acute respiratory syndrome‐coronavirus (SARS‐CoV)‐2′s origin is still controversial. Genomic analyses show SARS‐CoV‐2 likely to be chimeric, most of its sequence closest to bat CoV RaTG13, whereas its receptor binding domain (RBD) is almost identical to that of a pangolin CoV. Chimeric viruses can arise via natural recombination or human intervention. The furin cleavage site in the spike protein of SARS‐CoV‐2 confers to the virus the ability to cross species and tissue barriers, but was previously unseen in other SARS‐like CoVs. Might genetic manipulations have been performed in order to evaluate pangolins as possible intermediate hosts for bat‐derived CoVs that were originally unable to bind to human receptors? Both cleavage site and specific RBD could result from site‐directed mutagenesis, a procedure that does not leave a trace. Considering the devastating impact of SARS‐CoV‐2 and importance of preventing future pandemics, researchers have a responsibility to carry out a thorough analysis of all possible SARS‐CoV‐2 origins.

Keywords: BtCov/4991, furin cleavage site, Gain‐of‐function studies, pangolin CoV, RaTG13, receptor binding domain, SARS‐CoV‐2


The perfect binding ability of SARS‐CoV‐2 to human cells and the presence of the furin cleavage site, which is new for SARS‐like coronaviruses, might derive from genetic manipulation performed during evolutionary studies. By combining a bat coronavirus backbone and a receptor binding domain from pangolin coronavirus the resulting chimerawould seem completely natural.

An external file that holds a picture, illustration, etc.
Object name is BIES-9999-2000240-g004.jpg



Nearly a year has passed since the outbreak of severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) in Wuhan, China, and its origin is still controversial. Despite the international research effort conducted, a natural host, either direct or intermediate, has not yet been identified. The hypothesis that the Wuhan Huanan Seafood Wholesale Market was the first source for animal–human virus transmission has now been conclusively dismissedi and the few market samples that were collected showed only human‐adapted SARS‐CoV‐2, with no traces of zoonotic predecessor strainsii. Almost all scientific papers published to date purport that SARS‐CoV‐2 has a natural origin, and the only published paper considering possible a lab origin[ ] focuses on serial passage as the technique that could justify SARS‐CoV‐2 special adaptation to human cells. We here describe how the two main SARS‐CoV‐2 features, (1) the presence of a furin cleavage site missing in other CoVs of the same group and (2) an receptor binding domain (RBD) optimized to bind to human cells[ ] might be the result of lab manipulation techniques such as site‐directed mutagenesis. The acquisition of both unique features by SARS‐CoV‐2 more or less simultaneously is less likely to be natural or caused only by cell/animal serial passage.


Zhou et al.[ ] from the Wuhan Institute of Virology (WIV) were the first to identify and characterize a new coronavirus (CoV), SARS‐CoV‐2. The genomic sequences obtained from early cases shared 79% sequence identity to the CoVs that caused severe acute respiratory syndrome (SARS‐CoV) in 2002–2003 and 96.2% sequence identity to RaTG13 (MN996532), a CoV sequence detected from a Rhinolophus affinis bat. RaTG13 is currently the closest phylogenetic relative for SARS‐CoV‐2 found,[ ] but its complete genomic sequence was not published before the outbreak of SARS‐CoV‐2 and the original sample was collected in the Yunnan province (China) by the same group of WIV researchers in 2013. Zhou et al.[ ] stated to have found a match between SARS‐CoV‐2 and a short region of RNA‐dependent RNA polymerase (RdRp) of a CoV in their database and then fully sequenced the original sample collected in 2013, which they called RaTG13.

We discovered that the RdRp of RaTG13 has 100% nucleotide identity with the sequence BtCoV/4991 (KP876546), which was identified by Ge et al.[ ] in a Rhinolophus affinis bat in the Yunnan province in 2013, same location and year as RaTG13. BtCoV/4991 was collected in a mine colonized by bats near Tongguanzhen, Mojiang, Yunnan. The WIV researchers were invited to investigate the mine after six miners there had contracted severe pneumonia in 2012iii, and three of the miners have died.[ ] The miners have been tasked with clearing out bat droppings in the mine, and the severity of their pneumonia correlated with the duration of exposure to the mine.[ ] Four miners’ samples subsequently underwent testing at WIV, where Immunoglobulin G (IgG) antibodies against SARS were identified in all samples.[ ] Considering that only about 5300 people were infected in mainland China during the SARS outbreak of 2002–2004, most of whom resided in Guandong, the odds of four miners in Yunnan retaining antibodies from the 2002–2004 SARS outbreak are negligible. On the other hand, it is possible that the SARS antibody test administered to the miners cross‐reacted with a novel SARS‐like bat virus that the miners had acquired at the mine. Ge et al.[ ] have identified a number of CoVs in the mine, but based on the phylogenetic analysis, BtCoV/4991 was the only SARS‐related strain, clearly separated from all known alpha‐ and beta‐CoVs at that time. BtCoV/4991 was also different from other bat CoVs in the phylogenetic analysis carried out by Wang et al. in 2019.[ ] Chen et al.[ 10 ]  identified BtCoV/4991 as the closest sequence to SARS‐CoV‐2 because RaTG13 had not yet been published at that time. BtCoV/4991 and RaTG13 have been later asserted to be two different coding names of the same strain, as their original authors at WIV registered the two strains as one entry in the Database of Bat‐associated Viruses (DBatVir).iv

In late July 2020, Zhengli Shi, the leading CoV researcher from WIV, in an email interview [11 ] asserted the renaming of the RaTG13 sample and unexpectedly declared that the full sequencing of RaTG13 has been carried out as far back as in 2018 and not after the SARS‐CoV‐2 outbreak, as stated in Zhou et al.[ ] The reversal in WIV's stance on when exactly RaTG13 was fully sequenced could have been due to the discovery by independent researchers into the origins of SARS‐CoV‐2 that the filenames of the raw sequencing reads deposited by WIV on May 19, 2020v seem to indicate that sequencing for RaTG13 was done in 2017 and 2018.vi However, no formal erratum about year of sequencing and sample renaming from the authors of Zhou et al. [ ] has yet appeared, or as far as is currently known, has been submitted.

The second non‐human RdRp sequence closest to BtCoV/4991 (91.89% nucleotide identity) is the CoV sequence MP789 (MT084071) isolated in 2019 in a Malaysian pangolin (Manis javanica) from the Guangdong province (GD), China.[ 12 ] The envelope protein of MP789 shows surprisingly 100% aminoacidic identity with the corresponding protein in RaTG13, in bat‐SL‐CoVZXC21 (MG772934.1), in bat‐SL‐CoVZC45 (MG772933.1) and in some early SARS‐CoV‐2 isolates (e.g. YP_009724392).[ 13 ] The envelope protein of CoVs is involved in critical aspects of the viral lifecycle, such as viral entry, replication and pathogenesis.[ 14]


Many studies have reported that bats are natural reservoirs for a broad diversity of potentially pathogenic SARS‐like CoVs.[ 15 16 ] Some of these viruses can potentially directly infect humans[ 17 ], whereas others need to mutate their spike protein in order to effectively bind to the human angiotensin 1‐converting enzyme 2 (hACE2) receptor and mediate virus entry.[ 18 ] In order to evaluate the emergence potential of novel CoVs, researchers have created a number of chimeric CoVs, consisting of bat CoV backbones, normally unable to infect human cells, whose spike proteins were replaced by those from CoVs compatible with human ACE2. These chimeras were meant to simulate recombination events that might occur in nature.[ 19 20 ] Such gain‐of‐function experiments have raised a number of biosafety concerns and stirred controversy among researchers and the general public. One of the main arguments in favor of gain‐of‐function studies is the need to be prepared with an arsenal of drugs and vaccines for the next pandemic.[ 21 ] By contrast, one of the main arguments against them is that the next pandemic itself could be caused by those experiments, due to the risk of lab escape.[ 22 23 ]

In recent years, the field of corona‐virology had been focused on pan‐CoV therapies and vaccines, as evident from research conducted in the past 5 years,[ 24 25 26 27 ] as well as from media reports.vii Synthetically generating diverse panels of potential pre‐emergent CoVs was declared a goal of active grants for the EcoHealth Alliance, which funded some of such research at WIV, in collaboration with laboratories in the USA and other international partners.viii


Researchers have been generating chimeric CoVs for over two decades, long before the advent of modern sequencing or genetic engineering techniques. For example, in 1999, a group from Utrecht University used targeted RNA recombination to create a “cat‐and‐mouse” CoV chimera: the RBDs of a feline and murine CoV were swapped, demonstrating that this exchange swapped also species tropism during in vitro experiments.[ 28 ]

In 2007, the Shi group at WIV created a series of “bat‐man” CoV chimeric spike proteins while trying to determine what exactly confers CoVs the ability to jump from one species to another. The researchers used different segments of the spike protein of the human SARS virus to replace corresponding segments in the spike protein of a bat viral backbone. It was concluded that a relatively short region (aa 310 to 518) of the spike protein “was necessary and sufficient to convert Rp3‐S into a huACE2‐binding molecule,” 29 that is to provide the bat CoV spike protein with a novel ability of binding to a human ACE2 receptor.

In 2008, the Baric group at the University of North Carolina (UNC) took the WIV research one step further: instead of using human immunodeficiency viruses (HIV) pseudo‐viruses with bat CoV spike proteins, a live chimeric CoV was created. Following the experiments of their 2007 WIV colleagues, the Baric group used a bat SARS‐like CoV as a backbone and replaced its RBD with the RBD from human SARS.[ 30 ]

In 2015, the Shi and Baric groups joined forces and published probably the most famous gain‐of‐function virology paper, which described the creation of another synthetic chimeric virus.[ 19 ] This time the RBD of a mouse‐adapted SARS backbone (SARS‐MA15) was replaced by the RBD of RsSHC014, a bat strain previously isolated from Yunnan bats in 2011 by the Shi group. In 2016, the Baric group repeated their 2015 experiment using the same SARS‐MA15 backbone and the RBD from Rs3367,[ 31 ] a close relative of RsSHC014 also previously found in Yunnan by WIV and renamed “WIV1” after live culturing.[ 17 ]

Probably the largest reported number of novel chimeric viruses created was described in a 2017 paper from the Shi group at WIV,[ 15 ] in which the authors reported creating eight chimeric viruses using WIV1 as a backbone and transplanting into it various RBDs from bat SARS‐like viruses. These viruses were collected over a span of 5 years from the same cave near Kunming, Yunnan Province, where the Shi group originally found Rs3367 and RsSHC014. Only two of the eight live chimeric viruses were successfully rescued, and those two strains were found to possess the ability to bind to the human ACE2 receptor, as confirmed by experiments in hACE2‐expressing HeLa cells and RT‐PCR quantification of viral RNA.


The possibility that pangolins could be the intermediate host for SARS‐CoV‐2 has long been under discussion. [ 32 33 34 ] The biggest divergence between SARS‐CoV‐2 and RaTG13 is observed in the RBD of their spike proteins.[ ] Although its overall genome similarity is lower to SARS‐CoV‐2 than that of RaTG13, the MP789 pangolin strain isolated from GD pangolins has an almost identical RBD to that of SARS‐CoV‐2. Indeed, pangolin CoVs and SARS‐CoV‐2 possess identical amino acids at the five critical residues of the RBD, whereas RaTG13 only shares one amino acid with SARS‐CoV‐2.[ 35 ] ACE2 sequence similarity is higher between humans and pangolins than between humans and bats. Intriguingly, the spike protein of SARS‐CoV‐2 has a higher predicted binding affinity to human ACE2 receptor than to that of pangolins and bats.ix Before the SARS‐CoV‐2 outbreak, pangolins were the only mammals other than bats documented to carry and be infected by SARS‐CoV‐2 related CoV.[ 12 ] Recombination events between the RBD of CoV from pangolins and RaTG13‐like backbone could have produced SARS‐CoV‐2 as chimeric strain. For such recombination to occur naturally, the two viruses must have infected the same cell in the same organism simultaneously, a rather improbable event considering the low population density of pangolins and the scarce presence of CoVs in their natural populations.xMoreover, receptor binding studies of reconstituted RaTG13 showed that it does not bind to pangolin ACE2.xi


SARS‐CoV‐2 differs from its closest relative RaTG13 by a few key characteristics. The most striking difference is the acquisition in the spike protein of SARS‐CoV‐2 of a cleavage site activated by a host‐cell enzyme furin, previously not identified in other beta‐CoVs of lineage b[ 36 ] and similar to that of Middle East respiratory syndrome (MERS) coronavirus.[ 35 ] Host protease processing plays a pivotal role as a species and tissue barrier and engineering of the cleavage sites of CoV spike proteins modifies virus tropism and virulence.[ 37 ] The ubiquitous expression of furin in different organs and tissues have conferred to SARS‐CoV‐2 the ability to infect organs usually invulnerable to other CoVs, leading to systemic infection in the body.[ 38 ] Cell‐cultured SARS‐CoV‐2 that was missing the above‐mentioned cleavage site caused attenuated symptoms in infected hamsters,[ 39 ]and mutagenesis studies have confirmed that the polybasic furin site is essential for SARS‐CoV‐2′s ability to infect human lung cells.[ 40 ]

The polybasic furin site in SARS‐CoV‐2 was created by a 12‐nucleotide insert TCCTCGGCGGGC coding for a PRRA amino acid sequence at the S1/S2 junction (Figure 1). Interestingly, the two joint arginines are coded by two CGGCGG codons, which are rare for these viruses: only 5% of arginines are coded by CGG in SARS‐CoV‐2 or RaTG13, and CGGCGG in the new insert is the only doubled instance of this codon in SARS‐CoV‐2. The CGGCGG insert includes a FauI restriction site, of which there are six instances in SARS‐CoV‐2 and four instances in RaTG13 (and two in MP789). The serendipitous location of the FauI site could allow using restriction fragment length polymorphism (RFLP) techniques [41 ] for cloning [ 42 ] or screening for mutations, [ 43 ] as the new furin site is prone to deletions in vitro.[ 39 44 ]

An external file that holds a picture, illustration, etc.
Object name is BIES-9999-2000240-g001.jpg


Nucleotide sequence of the S protein at the S1/S2 junction in SARS‐CoV‐2 (NC045512.2) showing the furin cleavage site (in blue) that includes a FauI enzyme restriction site

A study by Zhou et al.[ 45 reported the discovery of a novel CoV strain RmYN02, which the authors claim exhibits natural PAA amino acid insertions at the S1/S2 cleavage site where SARS‐CoV‐2 has the PRRA insertion. However, upon close examination of the underlying nucleotide sequence of RmYN02 in comparison with its closest ancestors bat‐SL‐CoVZC45 and bat‐SL‐CoVZXC21, no insertions are apparent, just nucleotide mutations (Figure 2).

An external file that holds a picture, illustration, etc.
Object name is BIES-9999-2000240-g002.jpg


Alignment of nucleotide and amino acid sequences of the S protein from bat‐SL‐CoVZC45 (MG772933.1) and RmYN02 at the S1/S2 junction site. No insertions of nucleotides possibly evolving in a furin cleavage site can be observed (in blue)

Therefore, SARS‐CoV‐2 remains unique among its beta CoV relatives not only due to a polybasic furin site at the S1/S2 junction, but also due to the four amino acid insert PRRA that had created it. The insertion causes a split in the original codon for serine (TCA) in MP789 or RaTG13 to give part of a new codon for serine (TCT) and part of the amino acid alanine (GCA) in SARS‐CoV‐2 (Figure 3).

An external file that holds a picture, illustration, etc.
Object name is BIES-9999-2000240-g003.jpg


Alignment of nucleotide and amino acid sequences of the S protein from RaTG13 (MN996532), MP789 (MT084071) and SARS‐CoV‐2 (NC045512.2) at the S1/S2 site. The common nucleotides and amino acids are given in black, SARS‐CoV‐2 unique nucleotides and amino acids in red, RaTG13 unique nucleotides and amino acids in green and common nucleotides and amino acids in SARS‐CoV‐2 and RaTG13 that differ in MP789 in blue. The codon forserine (TCA) in RaTG13 and MP789 is split in SARS‐CoV‐2 to give part of a new codon forserine (TCT) and part of the amino acidalanine (GCA)

The insertion of the furin cleavage site in SARS‐CoV‐2 is not in frame with the rest of the sequence, when compared with the MP789 and the RaTG13 sequences (Figure 3). Therefore, it is possible to exclude that such insertion could have originated by polymerase slippage or by releasing and repriming, because insertion mutations generated by these mechanisms have been postulated to maintain the reading frame of the viral sequence.[ 46 ]The possibility that the furin cleavage site could have been acquired by recombination has been recently questioned by Seyran et al.,[ 47 ] because the SARS‐CoV‐2 spike protein seems to lack any further recombination event in contrast with the recombination model of other CoVs.


Due to the broad‐spectrum of research conducted over almost 20 years on bat SARS‐CoVs justified by their potential to spill over from animal to human,[ 48 ] a possible synthetic origin by laboratory engineering of SARS‐CoV‐2 cannot be excluded. The widely cited article of Andersen et al.[ stated that SARS‐CoV‐2 has most likely a natural origin. The main argument brought by the authors is that the high‐affinity binding of the SARS‐CoV‐2 spike protein to hACE2 could not have been predicted by models based on the RBD of SARS‐CoV. Based on the structural analysis conducted by Wan et al.,[ 49 SARS‐CoV‐2 has the potential to recognize hACE2 more efficiently than the SARS‐CoV, which emerged in 2002. Moreover, generation of CoV chimeric strains has recently demonstrated that bat CoV spikes can bind to the hACE2 receptor with more plasticity than previously predicted.[15 ] All amino acids in the RBD have been extensively analyzed and new models to predict ACE2 affinity are available.[ 50 ] In this regard, BatCoV Rs3367 (99.9% identity to WIV1) has been shown to share with SARS‐CoV‐2 four out of six critical residues in the RBD. Considering that WIV1 was shown to directly bind to hACE2, the same assumption could easily have been made about SARS‐CoV‐2 RBD.[ 51 ]

As described above, creation of chimeric viruses has been carried out over the years with the purpose of studying the potential pathogenicity of bat CoVs for humans. In this context, SARS‐CoV‐2 could have been synthesized by combining a backbone similar to RaTG13 with the RBD of CoV similar to the one recently isolated from pangolins[ 12 ], because the latter is characterized by a higher affinity with the hACE2 receptor. Such research could have aimed to identify pangolins as possible intermediate hosts for bat‐CoV potentially pathogenic for humans. Subsequent serial cell or animal passage, as described by Sirotkin & Sirotkin [ ] could have provided the perfect adaptation of the RBD to the hACE2.

Regarding the furin cleavage site, Andersen et al.[ ] state that “the functional consequence of the polybasic cleavage site in SARS‐CoV‐2 is unknown.” New studies from several groups have lately identified this activation site as possibly enabling the virus to spread efficiently between humans and attack multiple organs.[ 52 ] Experiments on proteolytic cleavage of CoV spike proteins have been recently suggested as future key studies to understand virus transmissibility in different hosts.[ 50 ]

Andersen et al.[ ] also state, based on the work of Almazan et al.[ 53 ] that “the genetic data irrefutably show that SARS‐CoV‐2 is not derived from any previously used virus backbone.” In the last 6 years before the outbreak of SARS‐CoV‐2 the number of potential bat backbones has been undeniably increased by several bat CoV screenings, last but not least bringing RaTG13 to scientific attention in January 2020. Other possible backbones could, as well, still wait for publication.

Andersen et al.[ ] affirm that “the acquisition of both the polybasic cleavage site and predicted O‐linked glycans also argues against culture‐based scenarios.” Methods for insertion of a polybasic cleavage site in infectious bronchitis CoV are given in Cheng et al.[54 ] and resulted in increased pathogenicity. Concerning the predicted O‐linked glycans around the newly inserted polybasic site, it should be noted that this prediction was not confirmed by Cryo‐EM inquiry into the SARS‐CoV‐2 spike glycoprotein.[ 55 ]Nevertheless, while it is true that O‐linked glycans are much more likely to arise under immune selection, they could be added in the lab through site‐directed mutagenesis[ 56 ] or arise in the course of in vivo experiments, for example, in BLT‐L mice with human lung implants and autologous human immune system[ 57 ] or in mice expressing the hACE2 receptor.[ 31 ] To overcome problems of bat CoV isolation, experiments based on direct inoculation of bat CoV in suckling rats have been carried out.[ 58 ] Humanized mice, ferrets, primates and/or other animals with similar ACE2 conformation could have all been used for serial passage experiments, as described in detail by Sirotkin and Sirotkin.[ ]

Andersen et al.[ ] also state that “subsequent generation of a polybasic cleavage site would have then required repeated passage in cell culture or animals with ACE2 receptors similar to those of humans, but such work has also not previously been described.” It should not be excluded that such experiments could have been aborted due to the SARS‐CoV‐2 outbreak, before a possible publication of the results or that the results were never intended to be published.

It is important to mention that RaTG13 and the pangolin CoV sequences from smuggled pangolins confiscated in the GD province in March 2019, and to which most of published papers supporting a natural origin of SARS‐CoV‐2 refer,[ ] have recently been questioned as to the accuracy of their assembly dataxii and require further analyses to prove their correctness.[ xiii , xiv ] It should also be noted that in vitro receptor binding studies of reconstituted RaTG13 yielded some peculiar results. [xi] The most surprising observation was that RaTG13, unlike SARS‐CoV‐2, is unable to bind ACE2 in R. macrotis bats, a close relative of RaTG13's purported host, R. affinis [ 59 ] (whose ACE2 receptor has not yet been tested). At the same time, RaTG13 was observed to bind hACE2[ 60 ], but not as well as ACE2 of rats and mice, to which SARS‐CoV‐2 did not bind at all. Is it possible that just as SARS‐MA15 was a mouse‐adapted strain of SARS, RaTG13 is actually a mouse‐adapted version of a CoV extracted from the Mojiang cave, rather than a strain obtained from a bat fecal swab? Unfortunately, the RaTG13 sample has been exhausted and it is no longer available for external examination,[ 11 ] which is unfortunate given a number of inconsistencies in its sequencing raw data. Also, the status and availability of the Mojiang miners’ samples remain as well an open and highly relevant question. Several samples from the miners have been collected[ ] and likely stored, and it would be of great value to test them for the presence of SARS‐CoV‐2‐like CoVs.

Another open question is the reason for modification and subsequent deletion of WIV's own viral database. In May 2020, several media outlets have reported that the change tracking system of WIV's internal database showed that the database was renamed from “Wildlife‐borne viral pathogen database” to “Bat and rodent‐borne viral pathogen database,” and its description was edited to replace instances of “wild animal” by “bat and rodent”; in addition, mention of “arthropod vectors” was deleted.xv The database description reported that it contained over 60 Mb of data in structured query language (SQL) format, but at as of early May 2020 the download link no longer worked.xvi Subsequently, the database page was taken down in its entirety but its snapshot is still available on Web Archive.xvii It is possible that other international CoV labs might have downloaded the SQL archive of the WIV database before it was taken down, in which case such groups should make those data publicly available.


The leak of highly dangerous pathogens from laboratories is not a rare event and occurrences have been documented in several countries. The most notable lab leak known is the 1977 H1N1 lab escape from China that caused a worldwide pandemic.[ 61 ] The most recent one is the November 2019 outbreak of brucellosis that occurred in two research centers in Lanzhou, China, infecting over 100 students and staff members.[ 62 ] Several lab escapes of the first SARS virus have been reported as well: in the summer of 2003 in Singapore,[ 63 ] then in December 2003 in Taiwan,xviii and in the spring of 2004 twice in China.xix

Concerns about WIV's lab safety were raised in 2018 by U.S. Embassy officials after visiting the Institute and having an interview with Zhengli Shi. The lab auditors summarized their worries in subsequent diplomatic cables to Washington.xx Chinese experts have also raised concerns about lab safety in their own country, lamenting that “lab trash can contain man‐made viruses, bacteria or microbes” and that “some researchers discharge laboratory materials into the sewer after experiments without a specific biological disposal mechanism.”xxi

American labs have also had their share of safety issues. Recently, research operations in the Biosafety level (BSL)‐4 United States Army Medical Research Institute of Infectious Diseases (USAMRIID) facility in Fort Detrick were interrupted in August 2019 following safety violations, in particular, relating to the disposal of infective materials.xxii Other US labs have been cited for safety issues as well. 22 ]

A number of scenarios causing SARS‐CoV‐2 to leak from a lab can be hypothesized. For example, an infected animal could have escaped from a lab or it could have scratched or bitten a worker (a concern raised in 2017 about the establishment of a BSL‐4 primate vaccine testing facility in Kunming, Yunnan[ 64 ]), or a researcher could have accidentally stuck themselves with inoculate (as happened in two cases in Russiaxxiii). Until 2020, CoVs were not considered particularly deadly or virulent. SARS‐like CoVs did not require BSL‐4 and could be manipulated under BSL‐2 and BSL‐3[ 42 ] conditions, making an accidental leak more likely. Aerosol experiments with CoVs[ 65 ] could result in lab leak as well, because a failure in the equipment used could go unnoticed for a long time before infection of lab workers is detected. Finally, the virus could potentially have leaked through the sewage system if proper waste disposal and/or decontamination procedures were not followed.


On the basis of our analysis, an artificial origin of SARS‐CoV‐2 is not a baseless conspiracy theory that is to be condemned[ 66 ] and researchers have the responsibility to consider all possible causes for SARS‐CoV‐2 emergence. The insertion of human‐adapted pangolin CoV RBD obtained by cell/animal serial passage and furin cleavage site could arise from site‐directed mutagenesis experiments, in a context of evolutionary studies or development of pan‐CoV vaccines or drugs. A recent article in Nature[ 67 ] affirms that a laboratory origin for SARS‐CoV‐2 cannot be ruled out, as researchers could have been infected accidentally, and that gain‐of‐function experiments resulting in SARS‐CoV‐2 could have been performed at WIV. Genetic manipulation of SARS‐CoV‐2 may have been carried out in any laboratory in the world with access to the backbone sequence and the necessary equipment and it would not leave any trace. Modern technologies based on synthetic genetics platforms allow the reconstruction of viruses based on their genomic sequence, without the need of a natural isolate.[ 68 ]

A thorough investigation on strain collections and research records in all laboratories involved in CoV research before SARS‐CoV‐2 outbreak is urgently needed. Special attention should be paid to strains of CoVs that were generated in virology laboratories but have not yet been published, as those possibly described in the deleted WIV database. Because finding a possible natural host could take years, as with the first SARS,[ 67 ] or never succeed, equal priority should be given to investigating natural and laboratory origins of SARS‐CoV‐2.

Xiao Qiang, a research scientist at Berkeley, recently stated: “To understand exactly how this virus has originated is critical knowledge for preventing this from happening in the future.” [xxi]


Rossana Segreto and Yuri Deigin do not have any conflicts of interest.


We are very grateful to Prof. Allan Krill (NTNU) for proof reading the manuscript, all the valuable comments and being open‐minded about controversial hypotheses; Prof. Heribert Insam (Head of the Department of Microbiology; University of Innsbruck) for his support and Dr. Lawrence Sellin for all the useful information. A special thanks goes to Dr. Fernando Castro‐Chavez (former Post‐Doc at the New York Medical College) for his support with Research Gate. We are very thankful to René Bergelt, for having discovered the database that confirmed our finding that BtCoV4991 and RaTG13 refer to the same sample. Finally, we are extremely grateful to members of the D.R.A.S.T.I.C. (Decentralised Radical Autonomous Search Team Investigating COVID‐19) Twitter group for all their work in uncovering many previously unpublished facts about SARS‐CoV‐2 and its relative strains. In particular, we are grateful to Luigi Warren for continuously probing the possible connection of the 2012 Mojiang pneumonia outbreak to WIV and SARS‐CoV‐2, to @TheSeeker268 for finding Chinese‐language 2013 Xu MSc and 2016 Huang PhD theses, which have confirmed the SARS‐like viral nature of the 2012 Mojiang pneumonia outbreak and have elucidated WIV's role in investigating that outbreak, including WIV's collection of the 4991/RaTG13 strain from the Mojiang mine, and to Francisco de Asis de Ribera Martin for providing us the English translation of the two theses, and also discovering the RaTG13 amplicon dates.


Segreto, R. , & Deigin, Y. (2020). The genetic structure of SARS‐CoV‐2 does not rule out a laboratory origin. BioEssays, 00, e2000240 10.1002/bies.202000240. [PMC free article][PubMed] [CrossRef] []

No external funding was received for this work.

Rossana Segreto and Yuri Deigin contributed equally to this study.


iAreddy, J. T. (2020). China rules out animal market and lab as coronavirus origin. The Wall Street Journalhttps://www.wsj.com/articles/china-rules-out-animal-market-and-lab-as-coronavirus-origin-11590517508 (last accessed on Oct 15, 2020).

iiZhan, S. H., Deverman, B. E., Chan, Y. A. (2020). SARS‐CoV‐2 is well adapted for humans. What does this mean for re‐emergence? BioRxivhttps://doi.org/10.1101/2020.05.01.073262 (last accessed on Oct 15, 2020).

iiiQiu, J. (2020). How China's ‘Bat Woman’ hunted down viruses from SARS to the new coronavirus. Sci. Amhttps://www.scientificamerican.com/article/how-chinas-bat-woman-hunted-down-viruses-from-sars-to-the-new-coronavirus1/ (last accessed on Oct 15, 2020).

ivDBatVir – The Database of Bat‐Associated Viruses. https://www.mgc.ac.cn/cgi-bin/DBatVir/main.cgi?func=accession&acc=MN996532 (last accessed on Oct 15, 2020).

vSRX8357956: amplicon sequences of RaTG13. https://www.ncbi.nlm.nih.gov/sra/SRX8357956(last accessed on Oct 15, 2020).

viAnon. (2020). Names of the RaTG13 amplicon sequences. https://web.archive.org/web/20200918174030/https://graph.org/RaTG13‐Amplicon‐Names‐07‐03 (last accessed on Oct 15, 2020).

viiKahn, J. (2020). How scientists could stop the next pandemic before it starts. NYT Magazine. https://www.nytimes.com/2020/04/21/magazine/pandemic-vaccine.html (last accessed on Oct 15, 2020).

viiiProject Number 2R01AI110964‐06, ECOHEALTH ALLIANCE, INC., https://projectreporter.nih.gov/project_info_description.cfm?aid=9819304&icde=49645421&ddparam=&ddvalue=&ddsub=&cr=1&csb=default&cs=ASC&pball=(last accessed on Oct 15, 2020).

ixPiplani, S., Singh, P. K., Winkler, D. A., Petrovsky, N. (2020). In silico comparison of spike protein‐ACE2 binding affinities across species; significance for the possible origin of the SARS‐CoV‐2 virus.arXivhttps://arxiv.org/abs/2005.06199 (last accessed on Oct 15, 2020).

xLee, J., Hughes, T., Lee, M.‐H., Field, H., Rovie‐Ryan, J. J., Sitam, F. T., … Daszak, P. (2020). No evidence of coronaviruses or other potentially zoonotic viruses in Sunda pangolins (Manis javanica) entering the wildlife trade via Malaysia. BioRxivhttps://doi.org/10.1101/2020.06.19.158717 (last accessed on Oct 15, 2020).

xiMou, H., Quinlan, B. D., Peng, H., Guo, Y., Peng, S., Zhang, L., … Farzan, M. (2020). Mutations from bat ACE2 orthologs markedly enhance ACE2‐Fc neutralization of SARS‐CoV‐2. BioRxivhttps://doi.org/10.1101/2020.06.29.178459 (last accessed on Oct 15, 2020).

xiiZhang, D. (2020). Anomalies in BatCoV/RaTG13 sequencing and provenance. Zenodohttps://zenodo.org/record/3969272 (last accessed on Oct 15, 2020).

xiiiSingla, M., Ahmad, S., Gupta, C., Sethi, T. (2020). De novo assembly of RaTG13 genome reveals inconsistencies further obscuring SARS‐CoV‐2 origins. Preprintshttps://doi.org/10.20944/preprints202008.0595.v1 (last accessed on Oct 12, 2020).

xivChan, Y. A., Zhan, S. H. (2020). Single source of pangolin CoVs with a near identical spike RBD to SARS‐CoV‐2. BioRxivhttps://doi.org/10.1101/2020.07.07.184374 (last accessed on Oct 15, 2020).

xvDevine, M. (2020). What is China covering up about the coronavirus? NYT Magazine. https://nypost.com/2020/05/06/what-is-china-covering-up-about-the-coronavirus-devine/ (last accessed on Oct 12, 2020).

xvi  (last accessed on Oct 15, 2020).

xviiBat and rodent‐borne viral pathogen database. https://web.archive.org/web/20200529174243/https://csdata.org/p/308/ (last accessed on Oct 15, 2020).

xviii: Reuters (2003). SARS case confirmed in Taiwan. Wiredhttps://www.wired.com/2003/12/sars-case-confirmed-in-taiwan/ (last accessed on Oct 13, 2020).

xixWalgate, R. (2004). SARS escaped Beijing lab twice. The Scientist Magazinehttps://www.the-scientist.com/news-analysis/sars-escaped-beijing-lab-twice-50137 (last accessed on Oct 15, 2020).

xxRogin, J. (2020). State Department cables warned of safety issues at Wuhan lab studying bat coronaviruses. The Washington Posthttps://www.washingtonpost.com/opinions/2020/04/14/state-department-cables-warned-safety-issues-wuhan-lab-studying-bat-coronaviruses/ (last accessed on Oct 15, 2020).

xxiCaiyu, L., Shumei, L. (2020). Biosafety guideline issued to fix chronic management loopholes at virus labs. Global Timeshttps://www.globaltimes.cn/content/1179747.shtml (last accessed on Oct 15, 2020).

xxiiGrady, D. (2020). Deadly germ research is shut down at army lab over safety concerns. NYTMagazine. https://www.nytimes.com/2019/08/05/health/germs-fort-detrick-biohazard.html (last accessed on Oct 15, 2020).

xxiii: Miller, J. (2004). Russian scientist dies in Ebola accident at former weapons Lab. NYTMagazine. https://www.nytimes.com/2004/05/25/world/russian-scientist-dies-in-ebola-accident-at-former-weapons-lab.html (last accessed on Oct 15, 2020).


xxiv  (last accessed on Oct 15, 2020).


Data sharing not applicable to this article as no datasets were generated or analysed during the current study.


1. Sirotkin, K. , & Sirotkin, D. (2020). Might SARS‐CoV‐2 have arisen via serial passage through an animal host or cell culture? A potential explanation for much of the novel coronavirus’ distinctive genome. BioEssays, 42, 1‐7. 10.1002/bies.202000091[PMC free article] [PubMed] [CrossRef] []

2. Andersen, K. G. , Rambaut, A. , Lipkin, W. I. , Holmes, E. C. , & Garry, R. F. (2020). The proximal origin of SARS‐CoV‐2. Nat. Med., 26, 450‐452. 10.1038/s41591-020-0820-9[PMC free article] [PubMed] [CrossRef] []

3. Zhou, P. , Yang, X. L. , Wang, X. G. , Hu, B. , Zhang, L. , Zhang, W. , … Shi, Z. L. (2020). A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature, 579, 270‐273. 10.1038/s41586-020-2012-7 [PMC free article] [PubMed] [CrossRef] []

4. Cagliani, R. , Forni, D. , Clerici, M. , & Sironi, M. (2020). Computational inference of selection underlying the evolution of the novel coronavirus, severe acute respiratory syndrome coronavirus 2. J. Virol., 94, 1‐11. 10.1128/jvi.00411-20 [PMC free article][PubMed] [CrossRef] []

5. Ge, X. Y. , Wang, N. , Zhang, W. , Hu, B. , Li, B. , Zhang, Y. Z. , … Shi, Z. L. (2016). Coexistence of multiple coronaviruses in several bat colonies in an abandoned mineshaft. Virol. Sin., 31, 31‐40. 10.1007/s12250-016-3713-9 [PMC free article] [PubMed] [CrossRef] []

6. Wu, Z. , Yang, L. , Yang, F. , Ren, X. , Jiang, J. , Dong, J. , … Jin, Q. (2014). Novel henipa‐like virus, mojiang paramyxovirus, in rats, China, 2012. Emerg. Infect. Dis., 20, 1064‐1066. 10.3201/eid2006.131022 [PMC free article] [PubMed] [CrossRef] []

7. Xu, L. (2013). The analysis of 6 patients with severe pneumonia caused by unknown viruses (Master's Thesis). Kunming Medical University, Emergency Medicine (professional degree). https://eng.oversea.cnki.net/Kcms/detail/detail.aspx?filename=1013327523.nh&dbcode=CMFD&dbname=CMFD2014

8. Huang, C. (2016). Novel virus discovery in bat and the exploration of receptor of bat coronavirus HKU9 (PhD Thesis). Chinese Center for Disease Control and Prevention. https://eng.oversea.cnki.net/kcms/detail/detail.aspx?dbcode=CDFD&dbname=CDFDLAST2018&filename=1017118517.nh

9. Wang, N. , Luo, C. , Liu, H. , Yang, X. , Hu, B. , Zhang, W. , … Shi, Z. (2019). Characterization of a new member of alphacoronavirus with unique genomic features in Rhinolophus bats. Viruses, 11(4), 379 10.3390/v11040379 [PMC free article] [PubMed] [CrossRef] []

10. Chen, L. , Liu, W. , Zhang, Q. , Xu, K. , Ye, G. , Wu, W. , … Liu, Y. (2020). RNA based mNGS approach identifies a novel human coronavirus from two individual pneumonia cases in 2019 Wuhan outbreak. Emerg. Microbes Infect., 9, 313‐319. 10.1080/22221751.2020.1725399 [PMC free article] [PubMed] [CrossRef] []

11. Cohen, J. (2020). Wuhan coronavirus hunter Shi Zhengli speaks out. Science, 369, 487‐488. 10.1126/science.369.6503.487 [PubMed] [CrossRef] []

12. Liu, P. , Chen, W. , & Chen, J. P. (2019). Viral metagenomics revealed sendai virus and coronavirus infection of malayan pangolins (Manis javanica). Viruses, 11(11), 979 10.3390/v11110979 [PMC free article] [PubMed] [CrossRef] []

13. Bianchi, M. , Benvenuto, D. , Giovanetti, M. , Angeletti, S. , Ciccozzi, M. , & Pascarella, S. (2020). Sars‐CoV‐2 envelope and membrane proteins: Structural differences linked to virus characteristics? Biomed. Res. Int., 2020 10.1155/2020/4389089 [PMC free article][PubMed] [CrossRef] []

14. Schoeman, D. , & Fielding, B. C. (2019). Coronavirus envelope protein: Current knowledge. Virol. J., 16, 1‐22. 10.1186/s12985-019-1182-0 [PMC free article] [PubMed] [CrossRef] []

15. Hu, B. , Zeng, L. P. , Yang, X. Lou , Ge, X. Y. , Zhang, W. , Li, B. , … Shi, Z. L. (2017). Discovery of a rich gene pool of bat SARS‐related coronaviruses provides new insights into the origin of SARS coronavirus. PLoS Pathog., 13, 1‐27. 10.1371/journal.ppat.1006698[PMC free article] [PubMed] [CrossRef] []

16. Fan, Y. , Zhao, K. , Shi, Z. L. , & Zhou, P. (2019). Bat coronaviruses in China. Viruses, 11(3), 210‐. 10.3390/v11030210 [PMC free article] [PubMed] [CrossRef] []

17. Ge, X. Y. , Li, J. L. , Yang, X. Lou , Chmura, A. A. , Zhu, G. , Epstein, J. H. , … Shi, Z. L. (2013). Isolation and characterization of a bat SARS‐like coronavirus that uses the ACE2 receptor. Nature, 503, 535‐538. 10.1038/nature12711 [PMC free article] [PubMed] [CrossRef] []

18. Graham, R. L. , & Baric, R. S. (2010). Recombination, reservoirs, and the modular spike: Mechanisms of coronavirus cross‐species transmission. J. Virol., 84, 3134‐3146. 10.1128/jvi.01394-09 [PMC free article] [PubMed] [CrossRef] []

19. Menachery, V. D. , Yount, B. L. , Debbink, K. , Agnihothram, S. , Gralinski, L. E. , Plante, J. A. , … Baric, R. S. (2015). A SARS‐like cluster of circulating bat coronaviruses shows potential for human emergence. Nat. Med., 21, 1508‐1513. 10.1038/nm.3985[PMC free article] [PubMed] [CrossRef] []

20. Johnson, B. A. , Graham, R. L. , & Menachery, V. D. (2018). Viral metagenomics, protein structure, and reverse genetics: Key strategies for investigating coronaviruses. Virology, 517, 30‐37. 10.1016/j.virol.2017.12.009 [PMC free article] [PubMed] [CrossRef] []

21. Racaniello, V. (2016). Moving beyond metagenomics to find the next pandemic virus. PNAS, 113, 2812‐2814. 10.1073/pnas.1601512113. [PMC free article] [PubMed] [CrossRef] []

22. Weiss, S. , Yitzhaki, S. , & Shapira, S. C. (2015). Lessons to be learned from recent biosafety incidents in the United States. Isr. Med. Assoc. J., 17, 269‐273. 10.1073/pnas.1601512113 [PubMed] [CrossRef] []

23. Casadevall, A. , & Imperiale, M. J. (2014). Risks and benefits of gain‐of‐function experiments with pathogens of pandemic potential, such as influenza virus: A call for a science‐based discussion. MBio, 5, 1‐5. 10.1128/mBio.01730-14 [PMC free article][PubMed] [CrossRef] []

24. Agostini, M. L. , Andres, E. L. , Sims, A. C. , Graham, R. L. , Sheahan, T. P. , Lu, X. , … Denison, M. R. (2018). Coronavirus susceptibility to the antiviral remdesivir (GS‐5734) is mediated by the viral polymerase and the proofreading exoribonuclease. MBio, 9, 1‐15. 10.1128/mBio.00221-18 [PMC free article] [PubMed] [CrossRef] []

25. Xia, S. , Liu, M. , Wang, C. , Xu, W. , Lan, Q. , Feng, S. , … Lu, L. (2020). Inhibition of SARS‐CoV‐2 (previously 2019‐nCoV) infection by a highly potent pan‐coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion. Cell Res., 30, 343‐355. 10.1038/s41422-020-0305-x [PMC free article] [PubMed] [CrossRef] []

26. Totura, A. L. , & Bavari, S. (2019). Broad‐spectrum coronavirus antiviral drug discovery. Expert Opin. Drug Discov., 14, 397‐412. 10.1080/17460441.2019.1581171[PMC free article] [PubMed] [CrossRef] []

27. Wang, Y. , Sun, Y. , Wu, A. , Xu, S. , Pan, R. , Zeng, C. , … Guo, D. (2015). Coronavirus nsp10/nsp16 Methyltransferase can be targeted by nsp10‐derived peptide in vitro and in vivo to reduce replication and pathogenesis. J. Virol., 89, 8416‐8427. 10.1128/jvi.00948-15[PMC free article] [PubMed] [CrossRef] []

28. Kuo, L. , Godeke, G. J. , Raamsman, M. J. B. , Masters, P. S. , & Rottier, P. J. M. (2000). Retargeting of coronavirus by substitution of the spike glycoprotein ectodomain: Crossing the host cell species barrier. J. Virol., 74, 1393‐1406. 10.1128/jvi.74.3.1393-1406.2000[PMC free article] [PubMed] [CrossRef] []

29. Maier, H. J. , Bickerton, E. , & Britton, P. (2015). Coronaviruses – Methods and protocols. London: Humana Press. []

30. Becker, M. M. , Graham, R. L. , Donaldson, E. F. , Rockx, B. , Sims, A. C. , Sheahan, T. , … Denison, M. R. (2008). Synthetic recombinant bat SARS‐like coronavirus is infectious in cultured cells and in mice. PNAS, 105, 19944‐19949. 10.1073/pnas.0808116105[PMC free article] [PubMed] [CrossRef] []

31. Menachery, V. D. , Yount, B. L. , Sims, A. C. , Debbink, K. , Agnihothram, S. S. , Gralinski, L. E. , … Baric, R. S. (2016). SARS‐like WIV1‐CoV poised for human emergence. PNAS, 113, 3048‐3053. 10.1073/pnas.1517719113 [PMC free article] [PubMed] [CrossRef] []

32. Li, X. , Zai, J. , Zhao, Q. , Nie, Q. , Li, Y. , Foley, B. T. , & Chaillon, A. (2020). Evolutionary history, potential intermediate animal host, and cross‐species analyses of SARS‐CoV‐2. J. Med. Virol., 92, 602‐611. 10.1002/jmv.25731 [PMC free article] [PubMed] [CrossRef] []

33. Lam, T. T. Y. , Jia, N. , Zhang, Y. W. , Shum, M. H. H. , Jiang, J. F. , Zhu, H. C. , … Cao, W. C. (2020). Identifying SARS‐CoV‐2‐related coronaviruses in Malayan pangolins. Nature, 583, 282‐285. 10.1038/s41586-020-2169-0 [PubMed] [CrossRef] []

34. Xiao, K. , Zhai, J. , Feng, Y. , Zhou, N. , Zhang, X. , Zou, J. J. , … Shen, Y. (2020). Isolation of SARS‐CoV‐2‐related coronavirus from Malayan pangolins. Nature, 583, 286‐289. 10.1038/s41586-020-2313-x [PubMed] [CrossRef] []

35. Zhang, T. , Wu, Q. , & Zhang, Z. (2020). Probable pangolin origin of SARS‐CoV‐2 associated with the COVID‐19 outbreak. Curr. Biol., 30, 1346‐1351.E2. 10.1016/j.cub.2020.03.022 [PMC free article] [PubMed] [CrossRef] []

36. Coutard, B. , Valle, C. , de Lamballerie, X. , Canard, B. , Seidah, N. G. , & Decroly, E . (2020). The spike glycoprotein of the new coronavirus 2019‐nCoV contains a furin‐ like cleavage site absent in CoV of the same clade. Antivir. Res., 176, 104742 10.1016/j.antiviral.2020.104742 [PMC free article] [PubMed] [CrossRef] []

37. Letko, M. , Marzi, A. , & Munster, V. (2020). Functional assessment of cell entry and receptor usage for SARS‐CoV‐2 and other lineage B betacoronaviruses. Nat. Microbiol., 5, 562‐569. 10.1038/s41564-020-0688-y [PMC free article] [PubMed] [CrossRef] []

38. Wang, Q. , Qiu, Y. , Li, J. Y. , Zhou, Z. J. , Liao, C. H. , & Ge, X. Y. (2020). A unique protease cleavage site predicted in the spike protein of the novel pneumonia coronavirus (2019‐nCoV) potentially related to viral transmissibility. Virol. Sin., 35, 337‐339. 10.1007/s12250-020-00212-7 [PMC free article] [PubMed] [CrossRef] []

39. Lau, S. , Wang, P. , Mok, B. W. , Zhang, A. J. , Chu, H. , Lee, A. C. , … Chen, H. (2020). Attenuated SARS‐CoV‐2 variants with deletions at the S1 / S2 junction. Emerg. Microbes Infect., 9, 837‐842. 10.1080/22221751.2020.1756700 [PMC free article][PubMed] [CrossRef] []

40. Hoffmann, M. , & Kleine‐Weber, H. (2020). A multibasic cleavage site in the spike protein of SARS‐CoV‐2 is essential for infection of human lung cells. Mol. Cell., 78, 779‐784.E5. 10.1016/j.molcel.2020.04.022 [PMC free article] [PubMed] [CrossRef] []

41. Kaundun, S. S. , Marchegiani, E. , Hutchings, S. J. , & Baker, K. (2019). Derived polymorphic amplified cleaved sequence (dPACS): A novel PCR‐RFLP procedure for detecting known single nucleotide and deletion – insertion polymorphisms. Int. J. Mol. Sci., 20(13), 3193 10.3390/ijms20133193 [PMC free article] [PubMed] [CrossRef] []

42. Zeng, L. P. , Gao, Y. T. , Ge, X. Y. , Zhang, Q. , Peng, C. , Yang, X. L. , … Shi, Z. L. (2016). Bat severe acute respiratory syndrome‐like coronavirus WIV1 encodes an extra accessory protein, ORFX, involved in modulation. J. Virol., 90, 6573‐6582. 10.1128/JVI.03079-15 [PMC free article] [PubMed] [CrossRef] []

43. Khan, S. G. , Muniz‐Medina, V. , Shahlavi, T. , Baker, C. C. , Inui, H. , Ueda, T. , … Kraemer, K. H. (2002). The human XPC DNA repair gene: Arrangement, splice site information content and influence of a single nucleotide polymorphism in a splice acceptor site on alternative splicing and function. Nucleic Acids Res., 30, 3624‐3631. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC134237/. [PMC free article] [PubMed] []

44. Liu, Z. , Zheng, H. , Lin, H. , Li, M. , Yuan, R. , Peng, J. , … Lu, J. (2020). Identification of common deletions in the spike protein of severe acute respiratory syndrome coronavirus 2. J. Virol., 94, e00790‐20. 10.1128/JVI.00790-20 [PMC free article] [PubMed] [CrossRef] []

45. Zhou, H. , Chen, X. , Hu, T. , Li, J. , Song, H. , Liu, Y. , … Shi, W. (2020). A Novel bat coronavirus closely related to SARS‐CoV‐2 contains natural insertions at the S1/S2 cleavage site of the spike protein. Curr. Biol., 30, 2196‐2203.E3. 10.1016/j.cub.2020.05.023[PMC free article] [PubMed] [CrossRef] []

46. Steinhauer, D. A. (1999). Role of hemagglutinin cleavage for the pathogenicity of influenza virus. Virology, 258, 1‐20. 10.1006/viro.1999.9716 [PubMed] [CrossRef] []

47. Seyran, M. , Pizzol, D. , Adadi, P. , El‐Aziz, T. M. A. , Hassan, S. S. , Soares, A. , … Brufsky, A. M. (2020). Questions concerning the proximal origin of SARS‐CoV‐2. J. Med. Virol., 03. 10.1002/jmv.26478 [PMC free article] [PubMed] [CrossRef] []

48. Wang, L. F. , & Anderson, D. E. (2019). Viruses in bats and potential spillover to animals and humans. Curr. Opin. Virol., 34, 79‐89. 10.1016/j.coviro.2018.12.007[PMC free article] [PubMed] [CrossRef] []

49. Wan, Y. , Shang, J. , Graham, R. , Baric, R. S. , & Li, F. (2020). Receptor recognition by the novel coronavirus from Wuhan: An analysis based on decade‐long structural studies of SARS coronavirus. J. Virol., 94(7), 1‐9. 10.1128/jvi.00127-20 [PMC free article] [PubMed] [CrossRef] []

50. Cui, J. , Li, F. , & Shi, Z. L. (2019). Origin and evolution of pathogenic coronaviruses. Nat. Rev. Microbiol., 17, 181‐192. 10.1038/s41579-018-0118-9 [PMC free article] [PubMed] [CrossRef] []

51. Fraguas Bringas, C. , & Booth, D. (2020). Identification of a SARS‐like bat coronavirus that shares structural features with the spike glycoprotein receptor‐binding domain of SARS‐CoV‐2. Access Microbiol., 10‐17. 10.1099/acmi.0.000166. [PMC free article] [PubMed] [CrossRef] []

52. Mallapati, S. (2020). Why does the coronavirus spread so easily between people?Nature, 579, 183 https://www.nature.com/articles/d41586-020-00660-x. [PubMed] []

53. Almazán, F. , Sola, I. , Zuñiga, S. , Marquez‐Jurado, S. , Morales, L. , Becares, M. , & Enjuanes, L. (2014). Coronavirus reverse genetic systems: Infectious clones and replicons. Virus Res., 189, 262‐270. 10.1016/j.virusres.2014.05.026 [PMC free article] [PubMed] [CrossRef] []

54. Cheng, J. , Zhao, Y. , Xu, G. , Zhang, K. , Jia, W. , Sun, Y. , … Zhang, G. (2019). The S2 subunit of QX‐type infectious bronchitis coronavirus spike protein is an essential determinant of neurotropism. Viruses, 11(10), 972 10.3390/v11100972 [PMC free article][PubMed] [CrossRef] []

55. Wrapp, D. , Wang, N. , Corbett, K. S. , Goldsmith, J. A. , Hsieh, C. L. , Abiona, O. , … McLellan, J. S. (2020). Cryo‐EM structure of the 2019‐nCoV spike in the prefusion conformation. Science, 367, 1260‐1263. 10.1126/science.abb2507 [PMC free article][PubMed] [CrossRef] []

56. Du, L. , Tai, W. , Yang, Y. , Zhao, G. , Zhu, Q. , Sun, S. , … Li, F. (2016). Introduction of neutralizing immunogenicity index to the rational design of MERS coronavirus subunit vaccines. Nat. Commun., 7, 1‐9. 10.1038/ncomms13473 [PMC free article] [PubMed] [CrossRef] []

57. Wahl, A. , De, C. , Abad Fernandez, M. , Lenarcic, E. M. , Xu, Y. , Cockrell, A. S. , … Garcia, J. V. (2019). Precision mouse models with expanded tropism for human pathogens. Nat. Biotechnol., 37, 1163‐1173. 10.1038/s41587-019-0225-9 [PMC free article] [PubMed] [CrossRef] []

58. Hu, D. , Zhu, C. , Ai, L. , He, T. , Wang, Y. , Ye, F. , … Wang, C. (2018). Genomic characterization and infectivity of a novel SARS‐like coronavirus in Chinese bats. Emerg. Microbes Infect., 7, 1‐10. 10.1038/s41426-018-0155-5 [PMC free article] [PubMed] [CrossRef] []

59. Hron, T. , Farkašová, H. , Gifford, R. J. , Benda, P. , Hulva, P. , Görföl, T. , … Elleder, D. (2018). Remnants of an ancient deltaretrovirus in the genomes of horseshoe bats (Rhinolophidae). Viruses, 10(4), 185‐. 10.3390/v10040185 [PMC free article] [PubMed] [CrossRef] []

60. Shang, J. , Ye, G. , Shi, K. , Wan, Y. , Luo, C. , Aihara, H. , … Li, F. (2020). Structural basis of receptor recognition by SARS‐CoV‐2. Nature, 581, 221‐224. 10.1038/s41586-020-2179-y [PMC free article] [PubMed] [CrossRef] []

61. Wertheim, J. O. (2010). The re‐emergence of H1N1 influenza virus in 1977: A cautionary tale for estimating divergence times using biologically unrealistic sampling dates. PLoS ONE, 5, 2‐5. 10.1371/journal.pone.0011184 [PMC free article] [PubMed] [CrossRef] []

62. Cyranoski, D. (2019). Chinese institutes investigate pathogen outbreaks in lab workers. Nature, https://www.nature.com/articles/d41586-019-03863-z [PubMed] []

63. Lim, P. L. , Kurup, A. , Gopalakrishna, G. , Chan, K. P. , Wong, C. W. , & Leo, Y. S. (2004). Laboratory‐acquired severe acute respiratory syndrome. N. Engl. J. Med., 350, 1740‐1745. 10.1056/NEJMoa032565 [PubMed] [CrossRef] []

64. Cyranoski D. (2017). Inside the Chinese lab poised to study world's most dangerous pathogens. Nature, 542, 399‐401 10.1038/nature.2017.21487 [PubMed] [CrossRef] []

65. Totura, A. , Livingston, V. , Frick, O. , Dyer, D. , Nichols, D. , & Nalca, A. (2020). Small particle aerosol exposure of African Green Monkeys to MERS‐CoV as a model for highly pathogenic coronavirus infection. Emerg. Infect. Dis., 26 10.3201/eid2612.201664. [PMC free article] [PubMed] [CrossRef] []

66. Calisher, C. , Carroll, D. , Colwell, R. , Corley, R. B. , Daszak, P. , Drosten, C. , … Turner, M. (2019). Statement in support of the scientists, public health professionals, and medical professionals of China combatting COVID‐19. The Lancet, 395, E42‐E43. 10.1016/S0140-6736(20)30418-9 [PMC free article] [PubMed] [CrossRef] []

67. Cyranoski, D. (2020). The biggest mystery: What it will take to trace the coronavirus source. Nature, 10.1038/d41586-020-01541-z. [PubMed] [CrossRef] []

68. Thao, T. T. N. , Labroussaa, F. , Ebert, N. , V'kovski, P. , Stalder, H. , Portmann, J. , … Thiel, V. (2020). Rapid reconstruction of SARS‐CoV‐2 using a synthetic genomics platform. Nature, 582, 561‐565. 10.1038/s41586-020-2294-9 [PubMed] [CrossRef] []



September 2021
1 2 3 4
5 6 7 8 9 10 11
12 13 14 15 16 17 18
19 20 21 22 23 24 25
26 27 28 29 30