My research has been focused on developing cutting-edge mass spec/proteomics technologies and protein bioengineering. Recently, we developed a robust proteomics pipeline to revolutionize nanobody (Nb)-drug discovery, and identified a large repertoire (> 8,000) of high-affinity, multi-epitope Nbs that target SARS-CoV-2 glycoprotein. Critically, we have demonstrated the outstanding preclinical efficacy of a stable, ultrapotent Nb for novel inhalation therapy of SARS-CoV-2 infection in a sensitive COVID-19 disease model. High-resolution cryoEM determination of Nb-bound structures reveals multiple potent neutralizing epitopes that target cryptic and conserved sites. Comparisons of neutralizing antibodies and Nbs provide insights into how Nbs target the spike to achieve high-affinity and broad activity. Structure-function analysis of Nbs indicates a variety of antiviral mechanisms. Our technologies will find broad utility in other devastating diseases including infectious diseases and cancer.
Inhalation COVID Therapy by Ultrapotent Nanobodies
The COVID-19 pandemic is driving the unprecedented transformation of the global medical research ecosystem through the search for effective new therapeutics that can help ease symptoms and prevent death among COVID-19 patients.