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Boston University coronavirus experiment reveals new weakness in omicron

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A controversial coronavirus experiment at Boston University has identified a mutation in the omicron variant that may help explain why it doesn’t seem as likely to sicken or kill as the original strain that emerged in China. The discovery could offer scientists a new target for designing therapies that limit the severity of covid.

The report, published on Wednesday in the journal Nature, comes three months after the researchers published an early version of the study that sparked a media firestorm, as well as confusion over who, exactly, funded the work and whether greater government oversight was required. .

In a laboratory experiment, the researchers combined the spike protein from an early omicron strain with the backbone of the original strain that emerged in Wuhan, China. The work, while not significantly different from several other experiments, has drawn media attention and raised fears that such manipulation of the coronavirus could trigger a more dangerous variant.

Proponents of the work claim that this experiment was pretty routine for pathogen research, which usually involves creating “recombinant” viruses that mimic what happens in nature. The experiment was conducted by researchers wearing multiple layers of protective gear inside a biosafety level 3 laboratory at the university’s ultra-secure National Laboratory for Emerging Infectious Diseases.

The goal of creating this “chimeric” virus, which the scientists dubbed Omi-S, was to try to understand which of the mutations in the omicron could be responsible for making it apparently less pathogenic – that is, less likely to create serious diseases – than the original strain.

The chimeric virus grew as omicron in cell cultures. Omi-S turned out to be just slightly less pathogenic in mice than the ancestral strain, with 80% mortality instead of 100%. It was even deadlier than the omicron.

Research has shown that the highly mutated omicron spike protein plays a role in making the variant less pathogenic than the ancestral strain. But the behavior of Omi-S suggested to lead researcher Mohsan Saeed, an assistant professor of biochemistry at Boston University, and other study co-authors that there must be something else contributing to the phenomenon.

The researchers kept experimenting and now claim to have found at least one missing piece of the puzzle: a mutation involving a protein called nsp6.

Unlike the spike protein studded on the surface of the coronavirus, nsp6 is a “nonstructural” protein, as its name suggests. The researchers point out that many proteins encoded by SARS-CoV-2 are not part of the mainframe of the coronavirus, but interact with the host in often mysterious ways.

“The reason why the role is important is the first time that there is another gene encoded by the SARS-CoV-2 virus that is involved in pathogenicity,” said Ronald Corley, chair of microbiology at Boston University Chobanian & Avedisian School of Medicine. .

“This represents a target protein for therapeutics,” said Corley, who is not a co-author of the paper but until recently was director of the lab.

The research attracted widespread attention in October after Saeed posted an early version of the study on the bioRxiv preprint server, where scientists have posted thousands of early drafts of their coronavirus research before formal peer review.

Critics of Pathogen Research have long argued that the field lacks adequate safety reviews and oversight, and that some experiments are too risky to justify any potential increase in knowledge. The Boston University experiment was seen as an example of “gain-of-function” research, in which a virus is manipulated to make it more transmissible or more pathogenic.

Corley and other supporters of the experiment argued that it actually made the ancestral strain less deadly in mice.

Complicating the debate was the uncertainty over whether the National Institutes of Health had funded the experiment. The original pre-printed version cited the NIH as one of the funding sources, but the university said the research was done independently. An NIH spokesperson later confirmed that the agency did not fund the work.

Robert F. Garry, a virologist at Tulane University who was not part of the study, said in an email that more research on nsp6 must be done to understand its significance. He also dismissed fears that such research was too dangerous.

“The very fact that it went through peer review should alert everyone to the fact that previous ‘concerns’ were exaggerated and alarmist,” Garry said.

The National Institutes of Health tasked a biosafety review board early last year to review all guidelines and protocols for research on potential pandemic pathogens, as well as what is known as “concerning dual-use research,” in which the research designed to benefit human health can also be weaponized.

The biosafety board has signaled that it will recommend broadening the definition of experiments that require special review. The board will release its report in the coming weeks, according to the NIH.