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Clinical grade ACE2 as a universal agent to block SARS-CoV-2 variants

  1. Author:
    Monteil, Vanessa [ORCID]
    Eaton, Brett
    Postnikova, Elena
    Murphy, Michael
    Braunsfeld, Benedict [ORCID]
    Crozier,Ian
    Kricek, Franz
    Niederhöfer, Janine
    Schwarzböck, Alice
    Breid, Helene
    Devignot, Stephanie [ORCID]
    Klingström, Jonas [ORCID]
    Thålin, Charlotte
    Kellner, Max J
    Christ, Wanda
    Havervall, Sebastian
    Mereiter, Stefan [ORCID]
    Knapp, Sylvia [ORCID]
    Sanchez Jimenez, Anna
    Bugajska-Schretter, Agnes [ORCID]
    Dohnal, Alexander [ORCID]
    Ruf, Christine
    Gugenberger, Romana
    Hagelkruys, Astrid [ORCID]
    Montserrat, Nuria [ORCID]
    Kozieradzki, Ivona [ORCID]
    Hasan Ali, Omar [ORCID]
    Stadlmann, Johannes [ORCID]
    Holbrook, Michael R [ORCID]
    Schmaljohn, Connie
    Oostenbrink, Chris [ORCID]
    Shoemaker, Robert H [ORCID]
    Mirazimi, Ali [ORCID]
    Wirnsberger, Gerald [ORCID]
    Penninger, Josef M [ORCID]

  2. Author Address

    Unit of Clinical Microbiology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden., NIAID Integrated Research Facility at Fort Detrick (IRF-Frederick), Frederick, Maryland, USA., Institute for Molecular Modeling and Simulation, University of Natural Resources and Life Sciences (BOKU), Vienna, Austria., Clinical Research Monitoring Program Directorate, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA., NBS-C BioScience & Consulting GmbH, Vienna, Austria., invIOs, Vienna, Austria., Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden., Department of Clinical Sciences, Karolinska Institute Danderyd Hospital, Stockholm, Sweden., Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria., Vienna BioCenter PhD Program, Doctoral School of the University at Vienna and Medical, University of Vienna, Vienna, Austria., Department of Medicine 1, Laboratory of Infection Biology, Medical University of Vienna, Vienna, Austria., Pluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain., Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain., Department of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver, Canada., Institute of Biochemistry, Department of Chemistry, University of Natural resources and Life, Sciences (BOKU), Vienna, Austria., Chemopreventive Agent Development Research Group, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.,
    1. Year: 2022
    2. Date: Jul 04
    3. Epub Date: 2022 07 04
  2. Journal: EMBO Molecular Medicine
    1. Pages: e15230
  4. Type of Article: Article
  5. Article Number: e15230
  1. Abstract:

    The recent emergence of multiple SARS-CoV-2 variants has caused considerable concern due to both reduced vaccine efficacy and escape from neutralizing antibody therapeutics. It is, therefore, paramount to develop therapeutic strategies that inhibit all known and future SARS-CoV-2 variants. Here, we report that all SARS-CoV-2 variants analyzed, including variants of concern (VOC) Alpha, Beta, Gamma, Delta, and Omicron, exhibit enhanced binding affinity to clinical grade and phase 2 tested recombinant human soluble ACE2 (APN01). Importantly, soluble ACE2 neutralized infection of VeroE6 cells and human lung epithelial cells by all current VOC strains with markedly enhanced potency when compared to reference SARS-CoV-2 isolates. Effective inhibition of infections with SARS-CoV-2 variants was validated and confirmed in two independent laboratories. These data show that SARS-CoV-2 variants that have emerged around the world, including current VOC and several variants of interest, can be inhibited by soluble ACE2, providing proof of principle of a pan-SARS-CoV-2 therapeutic. ©2022 The Authors. Published under the terms of the CC BY 4.0 license.

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External Sources

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  2. DOI: 10.15252/emmm.202115230
  3. PMID: 35781796

Library Notes

  1. Fiscal Year: FY2021-2022
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