Scientists from Scripps Research found an antibody dubbed J08 that seemed to be capable of both preventing and treating COVID-19.
They examined the blood of 14 COVID-19 survivors to find the most potent antibodies against the SARS-CoV-2 virus.
They then visualized exactly how J08 binds to different SARS-CoV-2 variants in different conformations, explaining what makes the monoclonal antibody so potent.
The findings suggest that the J08 antibody, because of its flexibility, will likely remain effective against future variants of COVID-19.
The research is published in the Proceedings of the National Academy of Sciences and was conducted by Andrew Ward et al.
In the study, the researchers determined the three-dimensional structure of J08 as it bound to the spike protein of SARS-CoV-2.
They confirmed that J08 successfully attached to the Alpha, Beta, Gamma and Delta variants and neutralized the viruses—preventing them from replicating.
However, J08 attached to the Omicron variant about 7 times more slowly, and then rapidly came off. About 4,000 times more J08 was needed to fully neutralize Omicron SARS-CoV-2 compared to the other variants.
The team says with variants other than Omicron, this antibody binds quickly and doesn’t come off for hours and hours.
With Omicron, the researchers were initially happy to find that it still binds, but it falls off very quickly. They identified the two structural changes that cause this.
The team showed that, for all the variants, J08 binds to a very small section of the virus—a section that generally stays the same even as the virus mutates.
Moreover, J08 could attach in two completely different orientations, like a key that manages to unlock a door whether it is right-side up or upside down.
The Omicron variant of SARS-CoV-2, however, had two mutations (known as E484A and Q493H) that changed the small area of the virus that directly interfaces with J08, anchoring it in place.
The team found that if just one of these mutations is present, J08 still manages to bind and neutralize the virus strongly, but mutations in both are what makes it less effective against the Omicron variant.
The researchers say the new results support the continued clinical trials of the monoclonal antibody-based on J08.
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