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

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

SARS-CoV-2*/drug effects ; SARS-CoV-2*/immunology ; Angiotensin-Converting Enzyme 2*/genetics ; Angiotensin-Converting Enzyme 2*/metabolism ; COVID-19*/virology ; COVID-19 Drug Treatment* ; Immunoglobulin Fc Fragments*/genetics ; Antiviral Agents*/pharmacology; Animals ; Cricetinae ; Mesocricetus ; Humans ; Disease Models, Animal ; Plants, Genetically Modified/metabolism ; Plants, Genetically Modified/genetics ; Spike Glycoprotein, Coronavirus ; Virus Replication/drug effects

Competing Interests: Declarations. Competing interests: K.Z. is co-founder and CEO of Zatloukal Innovations GmbH. The other authors declare no conflict of interest.
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.
(© 2025. The Author(s).)

Nat Commun. 2022 Jul 4;13(1):3840. (PMID: 35787633)
Cell Rep. 2022 Sep 13;40(11):111359. (PMID: 36075211)
Sci Adv. 2022 Dec 9;8(49):eabq6527. (PMID: 36475798)
Nat Rev Microbiol. 2024 Feb;22(2):75-88. (PMID: 38114838)
Plant Biotechnol J. 2008 May;6(4):392-402. (PMID: 18346095)
J Comput Chem. 2023 Feb 5;44(4):594-601. (PMID: 36398990)
EMBO Mol Med. 2022 Aug 8;14(8):e15230. (PMID: 35781796)
Emerg Infect Dis. 2020 Aug;26(8):. (PMID: 32396505)
BioDrugs. 2015 Aug;29(4):215-39. (PMID: 26177629)
Kidney Int. 2018 Jul;94(1):114-125. (PMID: 29691064)
Front Microbiol. 2022 May 04;13:840757. (PMID: 35602059)
Nat Commun. 2022 Feb 15;13(1):871. (PMID: 35169135)
Nat Commun. 2022 Feb 15;13(1):719. (PMID: 35169114)
J Virol. 2020 Oct 27;94(22):. (PMID: 32847856)
Nat Rev Immunol. 2023 Jun;23(6):381-396. (PMID: 36536068)
Biotechnol J. 2022 May;17(5):e2100422. (PMID: 35078277)
J Biol Chem. 2018 Apr 27;293(17):6363-6373. (PMID: 29523681)
EMBO Mol Med. 2012 Oct;4(10):1015-28. (PMID: 22837174)
Sci Transl Med. 2022 Jun 22;14(650):eabn7737. (PMID: 35471044)
J Sep Sci. 2021 Jan;44(1):35-62. (PMID: 32914936)
Front Bioeng Biotechnol. 2023 May 03;11:1180044. (PMID: 37207124)
Commun Biol. 2022 Nov 12;5(1):1237. (PMID: 36371561)
Immunology. 2022 Jul;166(3):380-407. (PMID: 35416297)
Lancet Infect Dis. 2022 Nov;22(11):e311-e326. (PMID: 35803289)
Front Plant Sci. 2021 Dec 06;12:742875. (PMID: 34938305)
iScience. 2022 Sep 16;25(9):104926. (PMID: 35992303)
Viruses. 2023 Apr 14;15(4):. (PMID: 37112944)
J Biol Chem. 2002 Apr 26;277(17):14838-43. (PMID: 11815627)
Trends Immunol. 2020 Dec;41(12):1100-1115. (PMID: 33132005)
J Virol. 2021 Sep 9;95(19):e0068521. (PMID: 34287040)
Biotechnol Adv. 2023 Oct;67:108197. (PMID: 37315875)
Nature. 2020 Jul;583(7818):834-838. (PMID: 32408338)
Biotechnol Adv. 2024 Oct;75:108403. (PMID: 38986726)
Virol Sin. 2021 Feb;36(1):141-144. (PMID: 32458296)
Nat Commun. 2021 Jun 21;12(1):3802. (PMID: 34155214)
Proc Natl Acad Sci U S A. 2020 Jul 14;117(28):16587-16595. (PMID: 32571934)
Cell Rep. 2023 Jan 31;42(1):111903. (PMID: 36586406)
Virol J. 2021 Jun 9;18(1):123. (PMID: 34107996)
Nat Methods. 2022 Apr;19(4):392-394. (PMID: 35396468)
Emerg Microbes Infect. 2021 Dec;10(1):797-809. (PMID: 33825619)
Nat Commun. 2023 Aug 25;14(1):5191. (PMID: 37626079)
Mol Syst Biol. 2020 Jul;16(7):e9610. (PMID: 32715618)
Front Plant Sci. 2021 Jan 07;11:604663. (PMID: 33584747)
Nat Commun. 2020 Nov 17;11(1):5838. (PMID: 33203860)
Biotechnol J. 2021 Jun;16(6):e2000566. (PMID: 33481336)
Cell Rep. 2021 Jul 20;36(3):109400. (PMID: 34245672)
Nat Rev Microbiol. 2023 Mar;21(3):162-177. (PMID: 36653446)
Curr Opin Virol. 2023 Oct;62:101349. (PMID: 37647851)
Biotechnol J. 2024 Jan;19(1):e2300319. (PMID: 37853601)
Front Chem. 2022 Apr 13;10:863118. (PMID: 35494652)
Elife. 2021 Dec 20;10:. (PMID: 34927585)
Pathog Immun. 2022 Aug 23;7(1):104-121. (PMID: 36072571)
Med. 2022 Apr 8;3(4):262-268.e4. (PMID: 35313451)
Commun Biol. 2023 May 12;6(1):513. (PMID: 37173421)
Molecules. 2023 Mar 13;28(6):. (PMID: 36985582)
Cell Discov. 2022 Jul 12;8(1):65. (PMID: 35821014)

P 35292 Austrian Science Fund; W 1224 Austrian Science Fund; P 31920 Austrian Science Fund; 101046133 ISIDORe

Keywords: ACE2; Antiviral; Plant-based expression platform; SARS-CoV-2

EC 3.4.17.23 (Angiotensin-Converting Enzyme 2)
EC 3.4.17.23 (ACE2 protein, human)
0 (Immunoglobulin Fc Fragments)
0 (Spike Glycoprotein, Coronavirus)
0 (Antiviral Agents)

SARS-CoV-2 variants

Date Created: 20250402 Date Completed: 20250403 Latest Revision: 20250405

20250407

PMC11965572

10.1038/s41598-025-95494-w

40175560