Engineered ACE2 receptor traps potently neutralize SARS-CoV-2
Anum Glasgow, Jeff Glasgow, Daniel Limonta, Paige Solomon, Irene Lui, Yang Zhang, Matthew A. Nix, Nicholas J. Rettko, Shoshana Zha, Rachel Yamin, Kevin Kao, Oren S. Rosenberg, Jeffrey V. Ravetch, Arun P. Wiita, Kevin K. Leung, Shion A. Lim, Xin X. Zhou, Tom C. Hobman, Tanja Kortemme, James A. Wells
Proceedings of the National Academy of Sciences Oct 2020, 202016093; DOI: 10.1073/pnas.2016093117
Significance
During the ongoing COVID-19 pandemic, protein engineering offers a rapid and powerful approach for building therapeutics to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. We use computational design, affinity maturation, and fusion to dimerization domains to engineer “receptor traps” based on wild-type angiotensin-converting enzyme II (ACE2), the target for viral spike-mediated SARS-CoV-2 entry into cells. The optimized ACE2 receptor traps neutralize authentic SARS-CoV-2 infections as effectively as high-affinity antibodies isolated from convalescent patients and also bind viral spike proteins from other coronaviruses known to cause respiratory diseases. ACE2 receptor traps have large binding interfaces and block the entire receptor binding interface, limiting the potential impact of viral escape mutations.
