French laboratory scientists could not mutate the bat virus to resemble SARS-CoV-2. why it matters

New Delhi: In a study that yielded potentially important clues about the origins of the COVID-19 pandemic, scientists at the Pasteur Institute in France experimented with a bat virus similar to SARS-CoV-2 and found a mutation to promote the evolution. Tried it causes human cells to adapt.

While the virus, named BANAL-236, was able to bind to human cells in Petri dishes, it failed to develop a key characteristic associated with transmission. This, the scientists said, indicated that it was likely that this trait of SARS-CoV-2 evolved in bats and not through a process of “silent circulation” among humans.

For their research, scientists isolated a strain of coronavirus – similar to SARS-CoV-2 – from bats in Laotian caves in mid-2020. Then he subjected it to various experiments.

one in February paper published in NatureResearchers said the virus can infect human cells by binding tightly to the same protein that SARS-CoV-2 uses to gain entry. However, it lacked the furin cleavage site, a feature that makes SARS-CoV-2 so easily transmissible.

Furin is an enzyme found in human cells. The amino acid in the spike protein of the SARS-CoV-2 virus has a unique orientation, and splits in two at the site when exposed to the enzyme. The furin cleavage site makes the virus uniquely suited to infect human cells and is believed to make it more permeable than its relatives.

the scientists then informed of In a June research paper (which has yet to be reviewed) that BANAL-236 had a very mild effect in laboratory animals. They found that while SARS-CoV-2 replicated rapidly in the lungs of mice, as seen in humans, BANAL-236 was unable to do so. Similarly, when two macaques were exposed to BANAL-236 via nasal spray, the effect was even milder, with the virus replicating in the intestines rather than in the lungs.

While evolutionary experiments with viruses can provide important scientific insights into pandemics, they have raised questions about safety and ethics.

Last year, experts debated the possibility of the spread of the Covid-19 pandemic following a laboratory leak. It was suggested that the Wuhan Institute of Virology is often Advantages of Function ExperimentsFrom where the virus might have leaked by mistake.

‘Gain of function’ is an area of ​​research focused on increasing generations of microorganisms, under conditions that cause mutations in viruses. Such experiments allow scientists to better predict emerging infectious diseases and develop vaccines and therapeutics.

Benefit of work research can use genetic engineering or serial passing. Genetic engineering involves ‘editing’ the genetic code by scientists to modify viruses in a predetermined way. Serial passing, meanwhile, involves allowing the pathogen to grow under different conditions and then observing the changes – which is what the team did in France.


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What do the findings reveal about Covid-19

The team at the Pasteur Institute wanted to investigate the possibility that SARS-CoV-2 entered the human population as a strain, like BANAL-236, that does not cause severe disease and is not highly contagious.

Scientists speculated that before the first clinical COVID-19 cases were detected in late 2019, the virus was circulating among humans until it developed a furin cleavage site and became fatal.

Taking advantage of the fact that BANAL-236 is unlikely to be fatal and causes only mild illness, the team conducted serial passage experiments.

The team removed lung tissue from mice infected with BANAL-236 and used the tissue to infect healthy animals. Then they repeated the cycle, transferring the virus from mouse to mouse.

In another experiment, they infected a dish of human intestinal cells with BANAL-236, then used the new virus produced by the cells to infect new dishes.

For both experiments, the team limited itself to six such transfers, To avoid the risk of creating a virus that can adapt to humans.

The team was unable to introduce the furin cleavage site of the BANAL-236 virus into any of the experiments. While the virus acquired new mutations, it did not get better at infecting mouse lungs or human cells.

The team suggests that their experiments show that the SARS-CoV-2 lineage acquired the furin site in bats before “spillover” into humans.

Arguing that the emergence of the furin site during “silent circulation” in humans was “unlikely”, the researchers noted: “Based on our work, it appears that the most likely hypothesis about the natural origin of the virus is the existence of a bat virus harboring a furin site that can infect humans directly or through other animal species. Is.”

The research team is now conducting further investigations to understand the origin of furin cleavage sites in caves located in China and its neighboring countries.

However, the researchers accepted the alternative hypothesis that “human infection may have occurred during experimental virus isolation in the laboratory”.

The implications of the Wuhan ‘lab leak’ theory

Experts have suggested that if BANAL-236 researchers cannot induce the virus to develop furin sites during serial pass experiments, it is unlikely that scientists in the Wuhan lab deliberately did this with SARS-CoV-2. could, as some of its supporters did. The “lab leak” theory has suggested.

“This is another nail in the coffin of the laboratory leak theory that by now should have been firmly sealed in the crypt,” was Edward Holmes, a virologist at the University of Sydney. Cited as saying new York Times,

However, other experts have recognized that the experiments in question were too small to reach any comprehensive conclusions.

(Edited by Asawari Singh)


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