COVID-19: Why is the “J08” monoclonal antibody so powerful?

The La Jolla team analyzed the blood of 14 COVID-19 survivors to identify the strongest antibodies once morest the SARS-CoV-2 virus. One of the main emerging molecules is the “J08” antibody, which appears capable of both preventing and treating COVID-19. J08 is undergoing stage II/III trials in Italy.

The antibody identified as the most potent once morest SARS-CoV-2

With this research, the team of virologists visualizes exactly how J08 binds to different variants of SARS-CoV-2 and explains what makes the monoclonal antibody so powerful. The study suggests that the J08 antibody, due to its flexibility, is likely to remain effective once morest future variants of COVID-19. Lead author Dr. Andrew Ward, professor of structural and integrative biology at Scripps Research, comments on the work: “While we can’t predict which variants of COVID-19 will emerge, understanding how J08 works once morest the virus may allow us to engineer even more potent antibodies.”

Exposures and Antibodies: when a person is exposed to a virus like SARS-CoV-2, their body generates a whole variety of antibodies that bind to different sections of the virus to eliminate it from the body. Scientists designing vaccines and treatments for COVID-19 are interested in some of these naturally produced antibodies, like J08, because of their effectiveness or “universality.” J08 appears to possess both of these characteristics, as it is found to be quite potent once morest a variety of COVID-19 variants.

The three-dimensional structure of J08 and its binding to the SARS-CoV-2 spike protein is deciphered here. The study confirms that J08 successfully binds Alpha, Beta, Gamma and Delta variants and manages to neutralize viruses and prevent them from replicating;

  • however, J08 binds the Omicron variant approximately 7 times slower,
  • and detaches very quickly…Thus, 4,000 times more J08 are needed to completely neutralize Omicron vs the other variants;
  • with Omicron, the antibody still binds, but it “falls off” very quickly.

2 structural changes involved in his weaknesses once morest Omicron: for all variants, J08 binds to a very small section of the virus, a section that usually remains unchanged, even when the virus mutates. J08 can also be fixed in 2 completely different orientations, like a key that manages to unlock a door, by turning it upside down or upside down. This small, flexible footprint is part of why J08 is resistant to so many mutations, however, in the case of Omicron, 2 mutations (called E484A and Q493H) modify this small area of ​​the virus which interfaces directly with J08. If only 1 of these mutations is present, J08 still manages to bind and strongly neutralize the virus, but if both mutations are present, then J08 is much less effective once morest Omicron. Which is unlikely, add the authors.

Despite these possible weaknesses, J08 is here confirmed as a potent monoclonal antibody once morest the different variants of SARS-CoV-2 and clinical trials are ongoing.

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