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Origins of COVID-19: the mysterious P4 laboratory in Wuhan reveals some of its secrets

In early 2020, just a few months after the start of the SARS-CoV-2 pandemic, the images are looping around the world. A market filled with exotic caged animals, a city in quarantine … In people’s minds, the scenario of the emergence of the COVID-19 is engraved: a bat has infected a pangolin passing by, follows a recombination of two viruses, and an epidemic that overflows thanks to a very busy wet market where humans and animals come together. Here is the start of a disaster movie. At least we believed so. Because a year and a half after the start of the most serious global health crisis for nearly a century, responsible for more than 3 million deaths to date, the doctrine of a “natural origin” of the well-tied virus appears moreover, in addition fragile, even obsolete.

As the mystery thickens around a possible zoonosis, the thesis of a contamination from the Wuhan virology laboratory grows thicker. While some researchers have warned of the need to explore this avenue as early as January 2020, against almost all of their colleagues, their voices are rarely heard. The exit of Donald Trump, in March 2020, does not help matters. The US President readily speaks of a “Chinese virus” and a “lab leak“(laboratory leak), but without ever providing the slightest proof. Quickly, this thesis, seen as a conspiracy theory, seems discredited. A year later, the situation has changed. The zoonotic origin of the epidemic remains the privileged track, but it is no longer taboo to speak of a possible laboratory accident. Like detectives, certain scientists have thus taken to the game, tracking down the slightest clue, the smallest trace left by the Chinese authorities on this mysterious Wuhan building classified P4.

On Twitter, a motley team called Drastic was formed to unearth certain elements on the institute of virology.

In France, the “Paris group” was formed in the fall of 2020 around the virologist Etienne Decroly, research director at the CNRS and at the University of Aix-Marseille. It brings together a few researchers who refuse to allow this track to be completely ruled out.

The least that can be said is that their findings are puzzling. If an animal origin of the epidemic deemed “probable to very probable” by the WHO investigation report, all is not settled. The much sought-after intermediate animal has still not been identified. A time presented as the pangolin, the latter now seems to be out of the question. If traces of the virus have been found in some specimens in China, everything now indicates that they have been contaminated by humans, and not the other way around. During the SARS-CoV-1 epidemic in 2002, the intermediate host – palm civet – was identified in just a few months.

Gilles Demaneuf, data analyst member of Drastic, estimates with L’Express that “the chances of an accident linked to a collection of viruses or an accidental exit from the P4 laboratory in Wuhan are around 70%”.

Why does such a theory attract so many researchers in a quest that has all of a good thriller?

The secret story of the famous “RaTG13”

To conduct the investigation, a step back is necessary. In 2012, six men were hospitalized in Kunming hospital, a large city in Yunnan province, some 1,500 km from Wuhan. All share more or less the same symptoms of severe pneumonia. They have in common to have worked in an abandoned mine in Tongguan, in the township of Mojiang. This mine is populated by colonies of “horseshoe” bats, or horseshoe bats. The six men spent up to two weeks extracting guano from the flying mammals on the floor of the galleries. This story, long forgotten, is disturbing since the symptoms of these six men resemble those of COVID-19.

Another interesting element: SARS-CoV-2 would come from this species of bat, according to the overwhelming majority of researchers. But how did this virus end up in Wuhan, a developed megalopolis that does not have colonies of these mammals?

As of January 23, 2020, researchers from the Wuhan Institute of Virology (WIV) are posting on a pre-publication site an article mentioning the discovery of the virus genetically closest to SARS-CoV-2. They baptize it “RaTG13”.

The genome of the newcomer is 96.2% identical to the virus responsible for COVID mystery thickens when Austrian biologist Rossana Segreto investigates the newcomer’s genetic matches with already known viruses.

Not without surprise, she realizes that RaTG13 has a twin known for a long time, and present in GenBank, the main public database of genetic sequences.

This twin, called “RaBtCoV / 4991” had been published by WIV researchers in the journal Virologica Sinica in 2016. The publication indicates another element: it had been taken during a sampling campaign carried out in 2013 in a mine disused town in Mojiang County.

Troubling coincidence. In July 2020, in an interview with the journal Science, Shi Zengli, patron of the P4 virology laboratory in Wuhan, confirms that RaTG13 is none other than RaBTCoV / 4991.

The virus was indeed taken from a horseshoe bat in the disused mine of Yunnan, the same one where the six men fell ill. Shi Zengli will however indicate in another interview with Scientific American that the juvenile pneumonia was due to a fungal infection.

“Nobody knew that at the time”

Pressed to answer questions from the scientific community, WIV researchers published in Nature on November 17, 2020 – almost a year after the start of the pandemic – details of the conditions for collecting RaTG13.

“Between 2012 and 2015, our group sampled bats once or twice a year in this cave and collected a total of 1,322 samples,” they write.

“In these samples, we found 293 very diverse coronaviruses, (…) of which 9 were classified as betacoronavirus (…), the latter all being related to SARS-type coronaviruses”.

It is one of these nine viruses, they add, which has been renamed RaTG13. The latter, they conclude, was sequenced in 2018.

After this publication, some scientists were moved to discover, in November 2020 therefore, that the WIV had nine unpublished coronaviruses in its fridges.

“Unless I am mistaken, nobody knew it at that time!”, Affirmed at the time in L’Express Etienne Decroly. So much mystery intrigues within the scientific community. To the point of wondering if an accident involving one of these coronaviruses could not have happened.

Coronavirus handling from 2013

If some consider these theories “fanciful”, others, like Etienne Decroly or Gilles Demaneuf, data-analayst member of Drastic, ask for “more advanced expertise in the matter”. Hervé Fleury, professor emeritus of virology at the CNRS and the University of Bordeaux, agrees. “We can not close this hypothesis, and some elements are disturbing,” he told L’Express. The researcher was interested in the literature of previous years, and found some interesting elements.

As early as 2013, a year after the illness of the Yunnan miners, Shi Zengli reported in a publication in Nature bat coronavirus “having a potential for passage to humans because it has the ability to bind to the human cell receptor ACE2”.

Of these viruses named W1V1, 3367 and SHCO14, W1V1 is cultured in cells and has the potential to “pass directly to humans without an intermediate host”, it is written.

“We are in 2013!” Exclaims Hervé Fleury.

In 2015, another publication in Nature Medicine (fruit of a collaboration between the same Chinese team from Wuhan and an American team from North Carolina) highlights the creation of “chimeras”, in particular from a SARS-type virus adapted to mice, and in which they introduced the Spike gene (or spicule) of SHC014.

Finally, in 2016, the American team launched the alert on bat viruses such as W1V1 which could pass directly to humans.

“As early as 2016, American and Chinese teams knew that viruses had the potential to infect human cells. W1V1 was therefore, four years ago, considered to be an immediate danger for humans,” the researcher warns.

Some of the experiments conducted at the Wuhan laboratory have even received funding from the US National Institutes of Health (NIH).

Because, thanks to the Spike protein, SARS-CoV-2 fits perfectly into human cells, despite a safety catch on the latter. The COVID-19 is therefore ideally suited to our mechanisms. This virus therefore acts like a burglar who would have the keys to a house.

What push some scientists to wonder: are these strange characteristics not the result of so-called “gain of function” experiments?

These experiments aim to force the evolution of a virus by repeating infections in laboratory animals or cell cultures. The idea is thus to better understand the nature of the molecular modifications which increase the transmissibility or the pathogenicity of viruses.

“It is very dangerous to handle such viruses, and accidents of this kind have already happened”, recalls Hervé Fleury.

In the years following the SARS outbreak of 2003, at least four laboratory leaks were detected.

Influenza A (H1N1) of 1977 was also caused by an error in human handling of a virus which would have circulated in the 1950s and which would have been preserved in the laboratory.

For the Bordeaux virologist, the hypothesis of such an accident “is not null”. “On the other hand,” he continues, “the presence of an intermediate host is not necessary, if we take the example of W1V1, and its quest could be a dead end, opportunely indicated by the Chinese regime. The experts would thus look elsewhere, far from the laboratory P4 of Wuhan “.

According to Washington Post, the United States Embassy in Beijing, after visits to the institute, alerted the American authorities in 2018 to security measures they considered insufficient.

Allegations refuted by Beijing, which denies that these laboratories are the source of the coronavirus. Regardless, the researchers, transformed into the Sherlock Holmes of the pandemic, still have their work cut out for them.