Enhanced binding and inhibition of SARS-CoV-2 by a plant-derived ACE2 protein containing a fused mu tailpiece

Sohee Lim, Hyung Jun Kwon, Dae Gwin Jeong, Hualin Nie, Sanghee Lee, Seo Rin Ko, Kyu Sun Lee, Young Bae Ryu, Hugh S. Mason, Hyun Soon Kim, Ah Young Shin, Suk Yoon Kwon

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Infectious diseases such as Coronavirus disease 2019 (COVID-19) and Middle East respiratory syndrome (MERS) present an increasingly persistent crisis in many parts of the world. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The angiotensin-converting enzyme 2 (ACE2) is a crucial cellular receptor for SARS-CoV-2 infection. Inhibition of the interaction between SARS-CoV-2 and ACE2 has been proposed as a target for the prevention and treatment of COVID-19. We produced four recombinant plant-derived ACE2 isoforms with or without the mu tailpiece (μ-tp) of immunoglobulin M (IgM) and the KDEL endoplasmic reticulum retention motif in a plant expression system. The plant-derived ACE2 isoforms bound whole SARS-CoV-2 virus and the isolated receptor binding domains of SARS-CoV-2 Alpha, Beta, Gamma, Delta, and Omicron variants. Fusion of μ-tp and KDEL to the ACE2 protein (ACE2 μK) had enhanced binding activity with SARS-CoV-2 in comparison with unmodified ACE2 protein derived from CHO cells. Furthermore, the plant-derived ACE2 μK protein exhibited no cytotoxic effects on Vero E6 cells and effectively inhibited SARS-CoV-2 infection. The efficient and rapid scalability of plant-derived ACE2 μK protein offers potential for the development of preventive and therapeutic agents in the early response to future viral outbreaks.

Original languageEnglish (US)
Article number2300319
JournalBiotechnology Journal
Issue number1
StatePublished - Jan 2024


  • ACE2
  • COVID-19
  • IgM mu tailpiece
  • SARS-CoV-2
  • plant expression system
  • plant molecular farming
  • recombinant protein

ASJC Scopus subject areas

  • Applied Microbiology and Biotechnology
  • Molecular Medicine


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