1. Generation of enzymatically competent SARS-CoV-2 decoy receptor ACE2-Fc in glycoengineered Nicotiana benthamiana.
- Author
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Castilho A, Schwestka J, Kienzl NF, Vavra U, Grünwald-Gruber C, Izadi S, Hiremath C, Niederhöfer J, Laurent E, Monteil V, Mirazimi A, Wirnsberger G, Stadlmann J, Stöger E, Mach L, and Strasser R
- Subjects
- Angiotensin-Converting Enzyme 2, Humans, Peptidyl-Dipeptidase A genetics, Peptidyl-Dipeptidase A metabolism, Protein Binding, Spike Glycoprotein, Coronavirus, Nicotiana genetics, Nicotiana metabolism, COVID-19, SARS-CoV-2
- Abstract
Human angiotensin-converting enzyme 2 (ACE2) is the primary host cell receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binding and cell entry. Administration of high concentrations of soluble ACE2 can be utilized as a decoy to block the interaction of the virus with cellular ACE2 receptors and potentially be used as a strategy for treatment or prevention of coronavirus disease 2019. Human ACE2 is heavily glycosylated and its glycans impact on binding to the SARS-CoV-2 spike protein and virus infectivity. Here, we describe the production of a recombinant soluble ACE2-fragment crystallizable (Fc) variant in glycoengineered Nicotiana benthamiana. Our data reveal that the produced dimeric ACE2-Fc variant is glycosylated with mainly complex human-type N-glycans and functional with regard to enzyme activity, affinity to the SARS-CoV-2 receptor-binding domain, and wild-type virus neutralization., (© 2021 The Authors. Biotechnology Journal published by Wiley-VCH GmbH.)
- Published
- 2021
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