An ACE2-Fc decoy produced in glycoengineered plants neutralizes ancestral and newly emerging SARS-CoV-2 variants and demonstrates therapeutic efficacy in hamsters.

Newly emerging SARS-CoV-2 variants of concern (VOCs) continue to drive COVID-19 waves and are typically associated with immune escape and increased resistance to current therapeutics including monoclonal antibodies. By contrast, VOCs still display strong binding to the host cell receptor ACE2. Consistent with these properties, we have now found that a soluble ACE2-Fc decoy produced in glycoengineered plants effectively neutralizes different SARS-CoV-2 isolates and exhibits even increased potency against VOCs as compared to an ancestral virus strain. In a golden Syrian hamster model, therapeutic intranasal delivery of ACE2-Fc effectively reduced weight loss and SARS-CoV-2 replication in the lungs when administered 24 h post-inoculation. This protective effect was not observed upon treatment of the infected animals with a non-binding ACE2-Fc mutant, demonstrating that the plant-derived ACE2-Fc decoy interferes specifically with the attachment of the virus to host cells. The results obtained provide support for further development of decoy-based antiviral approaches by plant molecular pharming.