Delivered as a nasal spray, newly engineered proteins called DARPins can prevent or treat COVID-19

In a study published in the journal Nature Chemical Biology, the lab of Zhilei Chen at Texas A&M University School of Medicine engineered two small and specifically targeted proteins that could be administered as a nasal spray to protect against and treat COVID-19.

The proteins were templated on the designed ankyrin repeat protein (DARPin), a synthetic scaffold inspired by a class of binding proteins commonly found in nature. Compared to conventional antibody-based drugs, DARPins are less prone to “go bad” during prolonged storage at moderate-to-high temperatures and can be made in large quantities at low cost.

In this study, the researchers created two DARPin molecules that assemble in groups of three and block the interaction between the primary protein used by the COVID-19 virus to enter cells and its partner on host cells, thus stopping the virus in its tracks. When delivered into the nose of animal models with the COVID-causing virus, the DARPins reduced the amount of virus that accumulate in the airways by up to 100-fold and significantly reduced disease progression. What’s more, the DARPins were effective not only against the original variant, but also all of the newer COVID-causing variants, including the omicron strain.

“This study offers the possibility of an on-demand nasal spray able to tackle COVID either before or after virus exposure,” Chen said. The team’s discovery provides another, potentially lower-cost therapeutic option for those who cannot receive traditional vaccines or are considered high risk.

The DARPin molecules were engineered by Vikas Chonira, with assistance from Rudo Simeon, both postdoctoral fellows in the Chen lab. This research is part of a larger collaborative effort that included Michael S. Diamond from Washington University; Peter D. Kwong from the National Institutes of Health; and Zhiqiang An from University of Texas Health Houston. Funding for the Chen lab is provided by the NIH New Innovator Award.