This Project Grant award from the National Institute of Allergy and Infectious Diseases, under the Allergy and Infectious Diseases Research program (CFDA 93.855), provides $867,563 to Rockefeller University to develop a pioneering class of nanobodies (engineered from llama immune systems) that can provide comprehensive protection against all beta-coronaviruses, including SARS-CoV-1, MERS-CoV, and SARS-CoV-2. The key objectives are to strategically expand the repertoire of highly neutralizing nanobodies, identify synergistic nanobody pairs that are resistant to viral mutations, and optimize the nanobodies for human use as both prophylactics and therapeutics administered intranasally or directly to the lungs. Deploying these nanobody combinations at the onset of a beta-coronavirus outbreak has the potential to protect first responders, limit transmission, and provide crucial support for immunocompromised individuals while new vaccines are developed. The award runs from February 2025 through January 2030.