Development of Plant-Produced Recombinant ACE2-Fc Fusion Protein as a Potential Therapeutic Agent Against SARS-CoV-2

Konlavat Siriwattananon, Suwimon Manopwisedjaroen, Phongthon Kanjanasirirat, Priyo Budi Purwono, Kaewta Rattanapisit, Balamurugan Shanmugaraj, Duncan R. Smith, Suparerk Borwornpinyo, Arunee Thitithanyanont, Waranyoo Phoolcharoen

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease (COVID-19) which has recently emerged as a potential threat to global public health. SARS-CoV-2 is the third known human coronavirus that has huge impact on the human population after SARS-CoV and MERS-CoV. Although some vaccines and therapeutic drugs are currently in clinical trials, none of them are approved for commercial use yet. As with SARS-CoV, SARS-CoV-2 utilizes angiotensin-converting enzyme 2 (ACE2) as the cell entry receptor to enter into the host cell. In this study, we have transiently produced human ACE2 fused with the Fc region of human IgG1 in Nicotiana benthamiana and the in vitro neutralization efficacy of the plant-produced ACE2-Fc fusion protein was assessed. The recombinant ACE2-Fc fusion protein was expressed in N. benthamiana at 100 μg/g leaf fresh weight on day 6 post-infiltration. The recombinant fusion protein showed potent binding to receptor binding domain (RBD) of SARS-CoV-2. Importantly, the plant-produced fusion protein exhibited potent anti-SARS-CoV-2 activity in vitro. Treatment with ACE2-Fc fusion protein after viral infection dramatically inhibit SARS-CoV-2 infectivity in Vero cells with an IC50 value of 0.84 μg/ml. Moreover, treatment with ACE2-Fc fusion protein at the pre-entry stage suppressed SARS-CoV-2 infection with an IC50 of 94.66 μg/ml. These findings put a spotlight on the plant-produced ACE2-Fc fusion protein as a potential therapeutic candidate against SARS-CoV-2.

Original languageEnglish
Article number604663
JournalFrontiers in Plant Science
Volume11
DOIs
Publication statusPublished - 7 Jan 2021

Keywords

  • ACE2-Fc fusion protein
  • COVID-19
  • Nicotiana benthamiana
  • SARS-CoV-2
  • molecular farming
  • plant-produced recombinant protein

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