Generation of enzymatically competent SARS-CoV-2 decoy receptor ACE2-Fc in glycoengineered Nicotiana benthamiana

Biotechnol J. 2021 Jun;16(6):e2000566. doi: 10.1002/biot.202000566. Epub 2021 Feb 12.

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.

Keywords: COVID-19; SARS-CoV-2; glycosylation; posttranslational modification; recombinant protein expression.

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • COVID-19*
  • Humans
  • Nicotiana / genetics
  • Nicotiana / metabolism
  • Peptidyl-Dipeptidase A / genetics
  • Peptidyl-Dipeptidase A / metabolism
  • Protein Binding
  • SARS-CoV-2*
  • Spike Glycoprotein, Coronavirus

Substances

  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Peptidyl-Dipeptidase A
  • Angiotensin-Converting Enzyme 2