Structural Biology, Alpacas, and Phages Join Forces to Combat the Evolving COVID-19 Virus

fang li, stanley perlman, michael farzan, lanying du

MINNEAPOLIS/ST. PAUL (09/26/2024) – Scientists at the University of Minnesota and the Midwest Antiviral Drug Discovery (AViDD) Center have developed a new strategy to keep antibody treatments effective against rapidly changing COVID-19 variants like Omicron. As the virus evolves, older treatments lose their potency. To address this, the team is using nanobodies – tiny antibodies from alpacas and llamas – and phages, which are viruses that attack bacteria, to stay ahead of the virus’s mutations.

Initially, the team had discovered a nanobody that worked well against early Omicron variants, but as the virus continued to evolve, its effectiveness dropped. By analyzing the structure of both the nanobody and the virus’s spike protein, the researchers introduced random changes to the nanobody, targeting areas close to the spike protein’s new mutations. Using phages to rapidly select the best-performing nanobodies, they developed one that is effective against the latest Omicron variants – all within just two weeks.

The study, published in PLOS Pathogens, was led by Dr. Fang Li, co-director of the Midwest AViDD Center and professor at the University of Minnesota Medical School, in collaboration with associate professor Dr. Bin Liu from the Hormel Institute, research scientist Dr. Gang Ye, and graduate student Fan Bu from the Department of Pharmacology.

“Our research shows that combining structural biology, nanobodies, and phages offers a powerful way to keep antibody therapies up to date with the evolving COVID-19 virus,” said Dr. Li. “This method could also be used to create treatments for other viruses.”

The research was funded by the NIH through several grants (R01AI089728, R01AI157975, and U19AI171954).

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