France – World | Mutation of an animal virus or laboratory accident: what do we know today about the origin of Covid-19?

2023-04-18 15:36:30

Etienne Decroly, among the very first, had lifted the hare, or rather the pangolin. In November 2020, when this funny scaly mammal was considered the number 1 suspect in the spread of Sars-Cov2 to humans, this new virus setting fire to the planet, this Marseille virologist, CNRS research director ( 1), made another assumption. The debate on the origins of Covid-19 was (already) polluted by conspiracy theses, such as the fable disseminated by Professor Luc Montagnier according to which SARS-CoV-2 would have been “made” from the AIDS virus. In the great scientific and media confusion of the beginnings of the Covid, Etienne Decroly, absent from TV sets, invisible on social networks, stuck to the only “scientific facts”. And they are disturbing.

In a collaborative study with bioinformaticians and phylogeny specialists published on October 27 in the CNRS Journal, the Marseille virologist undertook to read the history of the epidemic in the evolution of the virus genome, “a bit like questioning a family tree”, he explained to La Provence. Sars-CoV-2 belongs to the family of coronaviruses that infect many species of bats,”tanks” of these viruses. The genomic sequences of viral samples from patients infected at the start of the epidemic revealed an identity rate of 99.98%. Confirming that this viral strain transmissible between humans emerged very recently. But d where does it come from? The trail of RaTG13, a coronavirus collected in 2013 from bat excrement was ruled out by Decroly. “Its genome is 96% identical to that of Sars-CoV-2. But it remains too different to be directly at the origin of the pandemic”.

We must therefore look for a closer virus, in an intermediate host, a species in which the coronavirus could have evolved until it became capable of infecting humans. That’s why all eyes were on the pangolin, commonly sold in the market in Wuhan, where the outbreak began. In the genome of a coronavirus infecting these animals, the researchers discovered a virus, related to Sars-CoV-2, which contains a short genetic sequence very close, in a domain playing a key role in the entry of the virus into the human cells. But there again, “the rest of its genome is too different from that of Sars-CoV2 to be able to be a direct ancestor”, was able to determine the Marseille virologist. The innocent pangolin, there is therefore “a missing link”: “The bat and pangolin viruses are sort of the grandparents of Sars-CoV-2. But where is the direct parent?” In the absence of an identified intermediate host, or proof of a direct transfer in nature from bats to humans, the hypothesis of a laboratory accident must be “seen seriously” concluded Etienne Decroly.

“A puzzle with missing pieces”

Animal virus transmitted to humans or accidental laboratory leak? Three and a half years after the appearance of Covid-19, the enigma remains intact. And the opacity that the Chinese authorities oppose to the scientific community slows down the progress of knowledge. “It’s a puzzle with a lot of missing pieces” summarizes virologist Marc Eloit, head of the Pathogen Discovery laboratory at the Institut Pasteur and professor of virology at the National Veterinary School of Alfort, who today took part in a session of the National Academy of Medicine open to the press on the question of the origins of Sars-Cov2. A subject that remains essential to protect us from the emergence of a new epidemic.

As bats know no borders, the Institut Pasteur has worked in northern Laos, Vietnam and Cambodia, managing to identify the precursors of Sars-Cov2 in animals sampled in these areas and in bat excrement. “These are the closest viruses to Sars-Cov2 ever discovered, sometimes down to an amino acid”, explains Marc Eloit. Can these strains infect human populations in contact and evolve silently? Serological tests carried out on local populations gave no positive results. This species of bat studied by the Pasteur Institute is therefore officially exonerated.

Enough to revive the trail of the lab accident. With a first mystery: the appearance of Sars-Cov2 on the Wuhan market. “No outbreak has been declared before. If animals sold on this market were carriers of the virus, did they still transit, over hundreds of kms, without making any case elsewhere?”, asks microbiologist Patrick Berche. The low genetic diversity of Sars-Cov2 at the start of the epidemic also suggests an absence of prior circulation in animals.

Another disturbing fact: the sudden emergence of Sars-Cov 2 occurred a few kilometers from the Wuhan research center, which works in particular on coronaviruses, “with a bank that contains 15,000 bat samples”. Biosecurity issues are “unmistakable”, believes Patrick Berche, who recalls the precedent of the Russian H1N1 flu epidemic “caused by man, by a laboratory leak of a wild virus or a badly attenuated vaccine”.

And “70% of human epidemics come from zoonoses”with a natural crossing of barriers between species by random mutation or by co-infection and recombination between two viruses, so-called “gain of function” experiments are carried out in the laboratory, in order to identify virulence genes, predict the emergence of new viruses and drug design. “But the risk of accidents is significant”, alert Patrick Berche. In China, 8 institutions are working on coronaviruses, “with sometimes average levels of security”.

1. Luminy Architecture and Function of Biological Macromolecules Laboratory.

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