The report, published Wednesday in the journal Nature, comes three months after researchers published an early version of the study that sparked a media firestorm, as well as confusion over who, exactly, funded the work and it required greater government oversight.
In a lab experiment, researchers combined the spike protein from an early omicron line with the backbone of the original strain that emerged in Wuhan, China. The work, while little different from many other experiments, has attracted media attention and raised concerns that such manipulation of the coronavirus could trigger a more dangerous variant.
Proponents of the work counter that this experiment was quite common for pathogen research, which often involves creating “recombinant” viruses that mimic what happens in nature. The experiment was conducted by researchers wearing many layers of protective gear inside a biosafety level 3 lab at the university’s National Ultra-Secure Laboratory for Emerging Infectious Diseases.
The purpose of creating such a “chimeric” virus, which the scientists dubbed Omi-S, was to try to figure out which of the omicron mutations might be responsible for making it apparently less pathogenic – that is- ie less likely to create serious illness – than the original strain.
The chimeric virus grew like the omicron in cell cultures. Omi-S turned out to be only 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 omicron’s highly mutated spike protein plays a role in making the variant less pathogenic than the ancestral strain. But Omi-S’s behavior suggested to lead researcher Mohsan Saeed, 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 they 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 “non-structural” protein, as indicated by his name. The researchers point out that many proteins encoded by SARS-CoV-2 are not part of the central computer of the coronavirus but rather interact with the host in often mysterious ways.
“The reason the paper is important is that it’s the first time there’s been another gene encoded by the SARS-CoV-2 virus that’s been shown to be involved in pathogenicity,” said Ronald Corley, holder of the Boston University Chobanian Chair of Microbiology & Avedisian School of Medicine.
“This represents a target protein for therapeutics,” said Corley, who is not a co-author of the paper but was until recently director of the lab.
The research attracted widespread attention in October after Saeed posted an early draft of the study on preprint server bioRxiv, where scientists put thousands of early drafts of their coronavirus research ahead of formal review by pairs.
Criticisms of pathogen research have long argued that the field lacks adequate security reviews and oversight, and that some experiments are far too risky to warrant a potential increase in knowledge. The Boston University experiment has been seen as an example of “gain-of-function” research, in which a virus is manipulated in a way that could make it either more transmissible or more pathogenic.
Corley and other defenders of the experiment countered that it actually made the ancestral strain less lethal in mice.
Uncertainty about whether the National Institutes of Health funded the experiment complicated the debate. The original preprint version listed 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 had not funded 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 needs to be done to understand its significance. He also dismissed fears that such research is too dangerous.
“The mere fact that it passed peer review should alert everyone that the earlier ‘concerns’ were overblown and alarmist,” Garry said.
The National Institutes of Health appointed a biosafety review board early last year to review all research guidelines and protocols for potential pandemic pathogens, as well as what is known as the “dual-use research of concern”, in which research intended to benefit human health could also be weaponised.
The biosafety council has signaled that it will recommend expanding the definition of experiments requiring special review. The board will release its report in the coming weeks, according to the NIH.
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