Engineering human ACE2 to optimize binding to the spike protein of SARS coronavirus 2
Abstract
For severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to enter human cells, the spike protein on the surface of the virus must bind to the host receptor protein, angiotensin-converting enzyme 2 (ACE2). A soluble version of the receptor is being explored as a therapeutic. Chan et al. used deep mutagenesis to identify ACE2 mutants that bind more tightly to the spike protein and combined mutations to further increase binding affinity (see the Perspective by DeKosky). A promising variant was engineered to be a stable dimer that has a binding affinity for the spike protein; it is comparable with neutralizing antibodies and neutralized both SARS-CoV-2 and SARS-CoV-1 in a cell-based assay. In addition, the similarity to the natural receptor may limit the possibility for viral escape.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 04, 2020
- Source ID
- 10.1126/science.abc0870
Entities
People
- Andrew S Herbert
- Danielle Dorosky
- David M. Kranz
- Erik Procko
- John M Dye
- Kui K Chan
- Preeti Sharma
- Shawn A Abbasi
Organizations
- Geneva Foundation
- National Institute of Allergy and Infectious Diseases
- United States Army Medical Research Institute of Infectious Diseases
- University of Illinois Urbana–Champaign