Science

Origins of Covid-19: What the Latest Findings Tell Us (or Not)

The search for the origins of SARS-CoV-2 continues. Almost two years after the appearance of the virus responsible for the Covid-19 pandemic, scientists from the Institut Pasteur, in Paris and Laos, as well as from the University of Laos, discovered new coronaviruses very close to SARS-CoV-2. In an article published Sept. 17 on Research Square, the pre-publication site for the Nature group’s journals, the researchers presented a “breakthrough” thanks to samples taken from several hundred bats in northern Laos, near the border. with China. “This important discovery does not close the questions, but it shows that by multiplying the analyzes we can eliminate the shadows that remain in this crucial question of the origins of Covid-19,” Etienne Decroly, a virologist at the University of Aix, told L’Express -Marseilles.

Zoonotic origin or laboratory accident? The question remains unanswered, but this study demonstrates once again that the virus responsible for Covid-19 shares a genetic proximity with coronaviruses housed in insectivorous bats, those of the Rhinolophus group. Researchers at the Institut Pasteur were therefore interested in a region that is part of an immense karst relief, geological formations formed mainly by limestone, which is home to huge colonies of bats. “Laos shares this common territory with southern China, including many caves where these animals live, hence the idea of ​​studying the viruses they harbor,” explains Marc Eloit, director of the laboratory for “pathogen discovery” of the Institut Pasteur in Paris, whose teams analyzed the various samples collected. Because what happens there is representative of this common ecosystem with Yunnan.

Conclusions from the Institut Pasteur analyzes: The virus sequences found in bats are very close to those of SARS-CoV-2 and the researchers were able to demonstrate their ability to allow viruses to enter human cells. The genome of one of these viruses, called BANAL-52, even has 96.85% identity with SARS-CoV-2. Therefore, he is not his direct parent, but a cousin. So far, the closest coronavirus to this has been a strain called RaTG13, whose entire genetic sequence shows 96.2% identity to SARS-CoV-2. It was isolated in 2013 in a copper mine in Yunnan, southwest China, by researchers from the Wuhan Institute of Virology (WIV), the city where the Covid-19 pandemic broke out. Late 2019. Problem: RaTG13 differs from SARS-CoV -2 in a crucial point. It does not have the characteristics that give the virus responsible for the epidemic its ability to bind to human cells. This is a part of the Spike protein. The binding of this protein to the ACE2 receptor present on the surface of human cells is the first step in the infectious process. The subregion of the Spike protein that comes into contact with the ACE2 receptor is called the “RBD” (receptor-binding domain). However, three of the viruses that we discovered in Laos have an RBD capable of binding to the ACE2 receptor with a high affinity, similar to that of the first SARS-CoV-2 strains isolated at the beginning of the epidemic ”, explains Marc Eloit.

“Therefore, there may be viruses even closer to SARS-CoV-2 in this region, some of which may have this furin site.”

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What does this all mean? Simply put, these BANAL viruses can infect humans without an intermediate host. However, a crucial point remains to be elucidated. The genome of the viruses identified in Laos is missing a sequence called the “furin cleavage site,” which SARS-CoV-2 possesses, on the other hand. This element plays an important role in the fusion between the membrane of the virus and that of human cells. In other words, it allows the virus to better enter human cells and its existence conditions the pathogenicity of the virus. In summary, this discovery proves that coronaviruses capable of infecting humans, without being pathogens, exist in this geographical area – between southern China and the north of the Indochina peninsula. “Therefore, viruses even closer to SARS-CoV-2, some of which may have this furin site, may exist in this region. This may also have been acquired during an initial circulation, unidentifiable because asymptomatic, in the ‘ Man or other species, ‘says Marc Eloit.

“More complex than expected”

Clearly, the hypothesis of a natural origin of the virus is reinforced, but this discovery cannot definitively exclude the clue that leads to the Wuhan Institute of Virology. “This proves that the virus has the ability to cross the species barrier, passing directly from bats to humans. It would then have quietly circulated for several years in southwest China before mutating. And spread to Wuhan, which would then be just the place of superpropagation, “Jean-François Julien, ecologist and bat specialist at the Natural History Museum in Paris, told L’Express. All this being, of course, in the conditional. Because the path that leads SARS-CoV-2 from this limestone region to the Wuhan market stretches is still unknown.

There are still several hypotheses on the table. Despite these discoveries, the virus was able to traverse a species intermediate between bats and humans. But it has not yet been identified, despite numerous samples. Direct contamination may be at the source of the pandemic, far from Wuhan. According to a recent study previously published on the MedXriv server, approximately 400,000 people are infected each year with a SARS-CoV-type coronavirus, directly by a bat. Especially since, in this region, the inhabitants use bat droppings as fertilizer. These animals are also hunted for food. “Imagine that men enter these caves, to collect guano, for example, says Jean-François Julien. Horseshoe bats have the peculiarity of emitting ultrasound through their nostrils. Seeing these intruders, 20,000 individuals panic they start screaming and vaporizing a phenomenal amount of virus. ” . Cases of contamination of bats by Marburg fever have already been seen when humans simply stood under the colony, inhaling viruses exhaled by small mammals.

“These source viruses can have different histories, making it difficult to trace their origins.”

Another lesson from the Pasteur researchers’ discovery: In light of the complete genomes of five identified BANAL coronaviruses, that of SARS-CoV-2 turns out to be a real mosaic. In fact, it is the result of the recombination of at least five coronavirus genomes housed by different species of bats. Therefore, it could have arisen from several viruses and not from a single ancestor. “These source viruses can have a different history, which makes it difficult to trace the origin,” specifies Marc Eloit. “To continue with this research, we need more animal samples, but also serological analyzes of the inhabitants of these geographic areas prior to the start of the epidemic”, explains the researcher. If it were found that these viruses were already circulating before December 2019, the hypothesis of natural contamination would be confirmed. But to write the whole story, one would have to study the vast limestone reliefs on the other side of the border from Laos. Despite sampling, no virus has yet been found this close in Yunnan.

The thesis of a laboratory leak not ruled out

Meanwhile, the thesis of an accidental leak from a laboratory cannot be definitively ruled out. Therefore, a scientist could have been contaminated on site during a sample, or even in a laboratory before spreading the disease. “Proponents of animal transmission see in Pasteur’s study evidence of repeated direct contaminations between bats and humans. Proponents of the laboratory theory say, for their part, that it in no way explains how this virus reached Wuhan in a at a time when bats hibernate thousands of kilometers away, especially since BANAL viruses do not have a furin site, “explains Etienne Decroly. Shortly after the outbreak of the epidemic, virologists hypothesized that the presence of the furin site in SARS-CoV-2, which has never been found in a close bat coronavirus, ci, could indicate that it has been genetically modified.

This thesis is accentuated by the presence of the WIV in Wuhan. “It is a disturbing coincidence, that’s for sure, but this city is huge and is very connected to southern China. And the sale of exotic animals is very developed there,” tempera Jean-François Julien. Still, the elements question. In particular, the secrets surrounding the work done at WIV in the years before the outbreak of the pandemic. Sometimes according to the United States. According to an article published Sept. 7 in The Intercept, the US federal grant-funded NGO EcoHealth had the Wuhan Institute of Virology conduct a series of studies on bat coronaviruses. However, these funds would have allowed so-called “gain of function” experiments with these coronaviruses, although the US National Institutes of Health (NIH) has always denied funding such studies. In fact, it was necessary to make these viruses more virulent in order to study them and prevent the occurrence of a possible pandemic. If none of the viruses cited in these documents is genetically close to SARS-CoV-2, this proves that such experiments were carried out in Wuhan. And the veil has yet to be fully lifted on the scope of the research that took place there, which also fueled suspicions about this lab.

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Almost two years after the appearance of Covid-19, the puzzle that led to the outbreak of the pandemic is struggling to get the truth out. Because this research is at the same time: scientific, political and geopolitical.

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