More than two years after the appearance of the virus responsible for the Covid-19 pandemic, the search for the origins of SARS-CoV-2 continues. A study published this Wednesday in the scientific journal Nature identifies, in 46 species of bats (from six bat families) living in an area of northern Laos, three viruses very similar genetically to SARS-CoV-2, capable of infecting human cells. One of these strains could also be cultivated. A discovery that confirms a study by the Institut Pasteur published in the journal Research Square last September. Marc Eloit, head of the “Discovery of pathogens” laboratory at the Institut Pasteur (Paris), led the study and returns for L’Express to the main results. Interview.
L’Express: What are the main results of your latest study?
Marc Eliot: The first point: in bats that live in a very large limestone relief, shared between southern China, northern Laos and Vietnam, viruses extremely close to SARS-CoV-2 have been found and which are capable of infecting human cells. And in particular a 98% identical precursor, which recognizes human cells and attaches to them even better than the first isolates of Sars-CoV-2.
Second point: these viruses lack, in order to totally resemble Sars-CoV-2, a small site called “furin cleavage site”. This does not determine the infective capacity of cells, but determines the pathogenicity for humans. This therefore makes the hypothesis of a bat virus capable of infecting humans credible. Perhaps silently at first, before a more pathogenic strain appears.
What are we being told about knowing the origins of SARS-CoV-2?
The direct transmission of viruses from bats to humans – therefore without an intermediate animal – is quite possible. However, this virus did not appear where the bats live but in a megalopolis located much further, in Wuhan, 2,500 km from this limestone relief. This therefore raises the question of how it was transported.
Can we henceforth favor the hypothesis of zoonosis over that of a laboratory accident, which has not yet been ruled out?
No, we cannot prioritize it. There were several points about the laboratory, I would like to clarify them. Among the hypotheses, there was that of a virus entirely resulting from recombinations made in the laboratory. However, we realized that this virus present in nature could directly infect human cells, without prior manipulation. In other words, there is no need to postulate, for this part, any human intervention. Other viruses are also known for which multiplication in a host is sufficient to acquire a “furin site”. The fact that it is not found does not rule out the thesis that it was created in the laboratory, but there are also natural possibilities to explain its appearance.
What we do not explain for the moment is the transport several thousand kilometers away. The fact that this virus emerges in a city that hosts one of the few laboratories in the world working on bat coronaviruses may be pure coincidence, as it is. But it is an argument that suggests there may be a link to the activity of the Wuhan Virology Laboratory (WIV). Here again, this link can be direct: a virus is multiplied, the manipulator becomes contaminated and then it spreads in the population. Or it can come from people in the laboratory who have gone to collect samples in caves and who have returned home, with their families, contaminated.
Is there still the possibility of one or more intermediate hosts, relays between bats and humans?
Our research proves that there is no need to postulate the existence of such intermediate animals. Also, we haven’t found any yet. I also recall that with regard to MERS-CoV (Middle East respiratory syndrome) or SARS-CoV-1, the two coronaviruses having emerged in the last ten years, the intermediate host had very quickly been found . Which is currently not the case. Maybe that intermediate host just doesn’t exist.
Does this mean that a strain of the virus was able to circulate quietly, for a time, without being pathogenic?
To have this information, we would have to do retrospective surveys to see when the antibodies first appeared in a population. This is a usual approach for all emerging diseases. This is how, for example, it was discovered that the AIDS virus was circulating for more than ten years before it was identified. However, this data, a retrospective serological survey on a large scale, of a city like Wuhan for example, has never been done. Anyway, never published.
What do you have left to figure out?
Investigative efforts are continuing to see if there are viruses in bats that have a “furin site” directly. This remains an open hypothesis. We are also studying the phenotype of one of these strains, which we have succeeded in cultivating. We are looking at whether the virus can be transmitted from individual to individual, how its genome evolves, and if there are grounds for presupposing silent circulation.