A team led by Stanford has found two antibodies that can work together to defeat all the SARS-COV-2 variants. Additional research is necessary, but the approach could help develop treatments to keep up with the pace of evolving viruses.
The virus that causes the COVVI -19 was very good to mutate to continue to infect people – so good that most antibody treatments have developed during the pandemic are no longer effective. Now, a team led by researchers from the University of Stanford may have found a way to determine the virus constantly evolving and developing sustainable treatments.
The researchers discovered a method to use two antibodies, one to serve as an anchor type by focusing on an area of the virus that does not change much and another to inhibit the virus capacity to infect cells. This pairing of antibodies has proven to be effective against the initial SARS-COV-2 virus which caused the pandemic and all its variants by omicron in laboratory tests. The results are detailed in the newspaper Translational scientific medicine.
“Faced with a constantly evolving virus, we have designed a new generation of therapies that have the capacity to be resistant to viral evolution, which could be useful for many years later for the treatment of people infected with the SARS-COV-2,” said Christopher O. Barnes, main author of the study, Deputy Professor of Biology at the Stanford School of Humanities and the Sciences of Stanford.
A neglected option
The team led by Barnes and the first author Adonis Rubio, a doctoral student from the Stanford School of Medicine, conducted this survey using given antibodies of patients who had returned to COVID-19. Analyzing how these antibodies interacted with the virus, they found one that attaches to a region of the virus which does not often mutate.
This area, in the N-Terminal field, or NTD, had been neglected because it was not directly useful for treatment. However, when a specific antibody attaches to this area, it remains stuck to the virus. This is useful when designing new therapies that allow another type of antibodies to gain a foothold and get attached to the receptor link, or RBD, of the virus, essentially blocking the virus from the virus to receptors in human cells.
The researchers have designed a series of these double or “bispecific” antibodies, called COV2-Birn, and in laboratory tests, they showed a high neutralization of all the variants of SAR-COV-2 known to cause a disease in humans. Antibodies have also considerably reduced the viral load in the lungs of the mice exposed to a version of the Omicron variant.
Additional research, including clinical trials, should be carried out before this discovery could be used as treatment in human patients, but the approach is promising – and not only for the virus that causes COVID -19.
Then, the researchers will endeavor to conceive of bispecific antibodies which would be effective against all coronavirus, the family of viruses, including those which cause colds, the seas and the covid-19. This approach could potentially be also effective against flu and HIV, the authors said.
“Viruses are constantly evolving to maintain the ability to infect the population,” said Barnes. “To counter this, the antibodies that we develop must also evolve continuously to remain effective.”
Stanford’s additional authors include the first cycle in Megan Parada biology; Scientist of the Morgan Abernathy biology staff; The researcher in life sciences Yu E. Lee; The technician in the biology laboratory Michael Eso; The doctoral student in biophysics Gina El Nesr; And the former Israel Ramos, Teresia Chen and Jennie Phung laboratory technicians. Barnes is also affiliated with Chan Zuckerberg Biohub.
Rubio, BS ’21, is also affiliated with the Biology Department of the Human Sciences and Sciences School.
This work also includes co-authors from Rockefeller University, Fred Hutchinson Cancer Center in Seattle and Howard Hughes Medical Institute.
This research received the support of Chan Zuckerberg Biohub, the Howard Hughes Medical Institute, the National Institutes of Health, the National Science Foundation, the Pew Biomedical Scholars Program and the Rita Allen Foundation.
Rockefeller University has filed a provisional patent application in relation to monoclonal antibodies described in this work on which the Zijun Wang and Michel C. Nussenzweig co-authors from the University of Rockefeller are inventors (American patent 17/575,246). The co-authors Jesse D. Bloom by Fred Hutchinson Cancer Center consult for invivyd, apririri organic, the vaccine company, gsk and modernna. Bernadeta Dadononite, also from Fred Hutchinson Cancer Center, consults Moderna. Bloom and Dadononite are inventors of patents related to Fred Hutchinson Cancer Center linked to a deep viral mutational scan.
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