Boston University’s coronavirus experiment reveals a new weakness in omicronThank you for reading this post, don't forget to subscribe!
The reportpublished 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 whether it warranted greater government oversight.
In a laboratory experiment, the researchers combined the spike protein from an early omicron lineage with the backbone of the original strain that emerged in Wuhan, China. The work, although not significantly different from many other experiments, attracted media attention and raised concerns that such manipulation of the coronavirus could unleash a more dangerous variant.
Supporters of the work counter that this experiment is fairly routine for pathogen research, which often involves creating “recombinant” viruses that mimic what happens in nature. The experiment was conducted by researchers wearing multi-layered protective gear in a biosafety level 3 laboratory at the university’s ultra-secure National Laboratory for Emerging Infectious Diseases.
The purpose of creating such a “chimeric” virus, which the scientists named Omi-S, was to try to figure out which of the mutations in omicron might be responsible for making it seemingly less pathogenic—that is, less likely to cause severe disease – than the original strain.
The chimeric virus grows just like an omicron in cell cultures. Omi-S turned out to be only slightly less pathogenic in mice than the parent strain, with 80 percent mortality instead of 100 percent. It was still deadlier than an omicron.
The study showed that the highly mutated omicron spike protein played a role in making the variant less pathogenic than the parent strain. But Omi-S’s behavior 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 continued to experiment 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 dotted 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 instead interact with the host in ways that are often mysterious.
“The reason the paper is important is that for the first time there is another gene that is encoded by the SARS-CoV-2 virus that has been shown to be involved in pathogenicity,” said Ronald Corley, chair of microbiology at Boston University’s Chobanian & Avedisian School of Medicine.
“This represents a protein target for therapy,” said Corley, who did not co-author the paper but until recently was director of the lab.
The research gained widespread attention in October after Said published early version of the study on the preprint server bioRxiv, where scientists have placed thousands of early drafts of their coronavirus research prior to 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 is seen as an example of “gain-of-function” research, where a virus is manipulated in a way that can make it more transmissible or more pathogenic.
Corley and other defenders of the experiment countered that it actually made the ancestral strain less lethal in mice.
The debate was complicated by uncertainty over whether the National Institutes of Health funded the experiment. The initial preprint version cited the NIH as one of the funding sources, but the university said the research was done independently. An NIH spokesman later confirmed that the agency did not fund the work.
Robert F. Garry, a Tulane University virologist who was not involved in the study, said in an email that more research needs to be done on nsp6 to understand its significance. He also dismissed concerns that such research is too dangerous.
“The mere fact that it has passed peer review should alert everyone to the fact that previous ‘concerns’ are exaggerated and alarming,” Gary said.
The National Institutes of Health blamed a biosafety review board early last year with a review of all guidelines and protocols for research into potential pandemic pathogens, as well as what is known as “dual-use research of concern,” in which research intended to benefit human health can also be armed.
The Biosafety Board 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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