Engineering human ACE2 to optimize binding to the spike protein of SARS coronavirus 2. 2021-08-06. Jorma Jyrkkanen

Engineering human ACE2 to optimize binding to the spike protein of SARS coronavirus 2 View ORCID ProfileKui K. Chan1, View ORCID ProfileDanielle Dorosky2, View ORCID ProfilePreeti Sharma3, View ORCID ProfileShawn A. Abbasi2, View ORCID ProfileJohn M. Dye2, David M. Kranz3, View ORCID ProfileAndrew S. Herbert2,4, View ORCID ProfileErik Procko3,* See all authors and affiliations Science 04 Sep 2020: Vol. 369, Issue 6508, pp. 1261-1265 DOI: 10.1126/science.abc0870 Article Figures & Data Info & Metrics eLetters PDF A decoy receptor for SARS-CoV-2 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. Science, this issue p. 1261; see also p. 1167