A team led by Stanford has found two antibodies that can work together to defeat all SARS-COV-2 variants. More research is needed, but the approach could help in the development of treatments to maintain the rhythm of evolving viruses.
The virus caused by COVID-19 has been very good to mutate to continue infecting people, so well that most antibody treatments developed during the pandemic are no longer effective. Now, a team led by researchers at Stanford University may have found a way to specify the virus constantly evolving and develop more durable treatments.
The researchers discovered a method to use two antibodies, one to serve as a type of anchor when joining an area of the virus that does not change much and another to inhibit the virus’s ability to infect cells. It was shown that this antibody pairing is effective against the initial SARS-COV-2 virus that caused the pandemic and all its variants through OMICRON in laboratory tests. The findings are detailed in the newspaper Translational Medicine.
“Before a virus in constant change, we design a new generation of therapeutics that have the ability to be resistant to viral evolution, which could be useful for many years in the future for the treatment of people infected with SARS-COV-2,” said Christopher O. Barnes, leading author of the study, assistant professor of biology in Stanford schools of humanities of humanities and sciences and Sciences and Scholar at Stanford’s.
A pass overlooked
The team led by Barnes and the first author Adonis Rubio, a doctoral candidate at the Stanford Medicine School, conducted this research using donated antibodies from patients who had recovered from COVID-19. Analyzing how these antibodies interacted with the virus, they found one that adheres to a region of the virus that does not mutate often.
This area, within the n-terminal domain Spike, or NTD, had been overlooked because it was not directly useful for treatment. However, when a specific antibody adheres to this area, it remains attached to the virus. This is useful when designing new therapies that allow another type of antibody to obtain a support point and join the domain of union to the receiver, or RBD, of the virus, essentially blocking the virus of the union to the receptors in the human cells.
The researchers designed a series of these dual or “biespecific” antibodies, called COV2-BIRN, and in the laboratory tests they showed high neutralization of all SARS-COV-2 variants that are known to cause diseases in humans. The antibodies also significantly reduced the viral load in the lungs of the mice exposed to a version of the Omicron variant.
More investigations should be done, including clinical trials, before this discovery could be used as treatment in human patients, but the approach is promising, and not only for the virus caused by COVID-19.
Next, the researchers will work to design biespecific antibodies that would be effective against all coronavirus, the virus family, including those that cause common cold, Mers and Covid-19. Potentially, this approach could also be effective against influenza and HIV, the authors said.
“Viruses constantly evolve to maintain the ability to infect the population,” Barnes said. “To counteract this, the antibodies we develop must continually evolve to remain effective.”
The additional authors of Stanford include the University of Biology Megan Parada; Biology Staff scientist Morgan Abernathy; Yu E. Lee Life Science Researcher; Michael Biology Laboratory Technician; Biophysics Doctoral Student Gina el Nesr; and former Laboratory technicians Israel Ramos, Teresia Chen and Jennie Phung. Barnes is also affiliated with the Biohub by Chan Zuckerberg.
Rubio, BS ’21, is also affiliated with the Department of Biology of the School of Humanities and Sciences.
This work also includes co -authors from Rockefeller University, the Fred Hutchinson Cancer Center in Seattle and the Howard Hughes Medical Institute.
This research was supported by Chan Zuckerberg Biohub, the Howard Hughes Medical Institute, the National Health Institutes, the National Foundation of Sciences, the Pew Biomedical Scholars program and the Rita Allen Foundation.
The University of Rockefeller has submitted a provisional patent application in relation to monoclonal antibodies described in this work in which the co -authors Zijun Wang and Michel C. Nussenzweig of the Rockefeller University are inventors (US patent. 17/575,246). The Co -authors Jesse D. Bloom by Fred Hutchinson Cancer Center consultation for Invivyd, apriori bio, The Vaccine Company, GSK and modern. Bernadeta Dadonaite, also by Fred Hutchinson Cancer Center, consultation for modern. Bloom and Dadonaite are licensed patent inventors of the Fred Hutchinson Cancer Center related to deep viral mutational scan.