CORONAVIRUS – After two years of the pandemic and as our understanding of the Covid-19 grows every day, one question remains open: what is theorigin of the Sars-Cov2 coronavirus? Does it come from a wild animal or is it possible that it has leaked from a lab?
Researchers from the Institut Pasteur have brought an important stone to the building following studying 645 bats living in caves in Laos. There they discovered three coronaviruses very similar to the one we know so well, including one of the most similar ever analyzed.
Above all, these viruses are capable of infecting human cells, like Sars-Cov2. Never had such a capacity been observed in a coronavirus present in bats in Asia. This work was carried out in partnership with the Institut Pasteur in Laos and the country’s National University. The resultsunveiled early in September 2021, have just been reviewed and officially published this Wednesday, February 16 in Nature.
A coronavirus capable of infecting us
“These three coronaviruses close to Sars-Cov2 have a domain called RBD, located on the Spike protein, which allows it to bind to human cells. Of the 17 functionally important amino acids of this domain, there are only one or two that differ from those of Sars-Cov2”, explained in September to the HuffPost Professor Marc Eloit, Head of the Pathogen Discovery Laboratory at the Institut Pasteur.
After identifying the genome of these coronaviruses, the researchers synthesized this famous RBD protein, which allows Sars-Cov2 to infect us. In vitro, the researchers confirmed that it is able to bind to human cells. “We then grafted the entire spike onto harmless pseudoviruses which managed to enter human cells”, continued Marc Eloit.
Better: the researchers managed to keep these viruses alive. “Which should allow us to test whether it can cause disease,” said the professor. For this, the researchers plan to infect modified mice with these three coronaviruses that are contaminated in the same way as humans and see if this makes them sick. Because if these coronaviruses are capable of infecting humans, it is not said that they can harm us.
Indeed, Sars-Cov2 has two very surprising properties, which have never been found on a coronavirus of this type. First, this RBD domain, which makes it possible to infect human cells. But also a “furin cleavage site”, a feature that makes the virus much more contagious by improving its ability to penetrate our cells. Without this feature, it is possible that discovered coronaviruses might infect humans, but not enough to cause disease.
“It is possible that these viruses are low pathogenic, circulating and infecting populations in contact with bats, preventing superinfection by more pathogenic viruses, as a vaccine would. It is also possible that by dint of circulating in humans silently, such a virus acquired, at some point, a furin site and became more pathogenic”, detailed Marc Eloit.
The researcher is working precisely on these tracks and hopes to be able to carry out serological tests of the inhabitants living near these caves in Laos to verify this hypothesis.
The origin of Covid-19 remains a mystery
These studies, if confirmed, do not directly answer the question of the origin of Sars-Cov2. In particular because these viruses do not have this famous furin site. How did the coronavirus that we know manage to acquire this functionality?
Marc Eloit thinks of three hypotheses: either there are many coronaviruses that incubate in bats in Asia that have not yet been discovered, or one of these coronaviruses has acquired the right mutation by silently circulating in humans or a other terrestrial animal, or it is an acquisition that took place in the laboratory.
This last thesis notably came back to the fore in early 2021 when researchers asked China to allow real and in-depth investigations into the origins of Covid-19 (more details in our dedicated articles, here and to be).
The discovery by researchers from the Institut Pasteur, on the other hand, dismisses certain bundles of clues which made it possible to go back to the famous laboratory specializing in coronaviruses located in Wuhan, epicenter of the Covid-19 pandemic.
The pangolin, collateral victim
Thus, the closest known relative of Sars-Cov2 so far, RATG13, came from a cave in Yunnan. It had been studied in 2013 in the Wuhan laboratory. But this coronavirus had a very different RBD, so it doesn’t seem capable of easily infecting humans. However, the work of Marc Eloit demonstrates that the acquisition of this characteristic is possible naturally, without the need for human intervention.
“The argument that the RBD of Sars-Cov2 is too well adapted to humans and might only have been created in the laboratory no longer really holds up with our work, because we see that coronaviruses with such an RBD exist in naturally occurring bats. On the other hand, our work does not provide any information as to the origin of the furin site, which is important for the pathogenicity of SARS-CoV-2,” explained the professor.
On the other hand, there is an animal that these works whiten: the pangolin. In the early months of the pandemic, this small mammal was suspected of being the intermediate host in which a coronavirus succeeded in developing the characteristics allowing it to infect humans (in particular the RBD and the furin site). But this new release changes that.
“The pangolin may have appeared as a crucible, because coronaviruses were found in this animal with an RBD closest to Sars-Cov2. With the viruses that have been found, the Pangolin no longer appears as a possible intermediary. But more likely a collateral victim, infected by bats”, detailed Marc Eloit. The question of the origin of the coronavirus remains open, but at least the pangolin seems bleached.
See also on The HuffPost: Variant Deltacron, multiple mutations… when to worry?