EMBO Molecular Medicine (Aug 2022)
Clinical grade ACE2 as a universal agent to block SARS‐CoV‐2 variants
- Vanessa Monteil,
- Brett Eaton,
- Elena Postnikova,
- Michael Murphy,
- Benedict Braunsfeld,
- Ian Crozier,
- Franz Kricek,
- Janine Niederhöfer,
- Alice Schwarzböck,
- Helene Breid,
- Stephanie Devignot,
- Jonas Klingström,
- Charlotte Thålin,
- Max J Kellner,
- Wanda Christ,
- Sebastian Havervall,
- Stefan Mereiter,
- Sylvia Knapp,
- Anna Sanchez Jimenez,
- Agnes Bugajska‐Schretter,
- Alexander Dohnal,
- Christine Ruf,
- Romana Gugenberger,
- Astrid Hagelkruys,
- Nuria Montserrat,
- Ivona Kozieradzki,
- Omar Hasan Ali,
- Johannes Stadlmann,
- Michael R Holbrook,
- Connie Schmaljohn,
- Chris Oostenbrink,
- Robert H Shoemaker,
- Ali Mirazimi,
- Gerald Wirnsberger,
- Josef M Penninger
Affiliations
- Vanessa Monteil
- Unit of Clinical Microbiology Karolinska Institutet and Karolinska University Hospital Stockholm Sweden
- Brett Eaton
- NIAID Integrated Research Facility at Fort Detrick (IRF‐Frederick) Frederick Maryland USA
- Elena Postnikova
- NIAID Integrated Research Facility at Fort Detrick (IRF‐Frederick) Frederick Maryland USA
- Michael Murphy
- NIAID Integrated Research Facility at Fort Detrick (IRF‐Frederick) Frederick Maryland USA
- Benedict Braunsfeld
- Institute for Molecular Modeling and Simulation University of Natural Resources and Life Sciences (BOKU) Vienna Austria
- Ian Crozier
- Clinical Research Monitoring Program Directorate Frederick National Laboratory for Cancer Research Frederick Maryland USA
- Franz Kricek
- NBS‐C BioScience & Consulting GmbH Vienna Austria
- Janine Niederhöfer
- invIOs Vienna Austria
- Alice Schwarzböck
- invIOs Vienna Austria
- Helene Breid
- invIOs Vienna Austria
- Stephanie Devignot
- Unit of Clinical Microbiology Karolinska Institutet and Karolinska University Hospital Stockholm Sweden
- Jonas Klingström
- Center for Infectious Medicine Department of Medicine Huddinge Karolinska Institutet Stockholm Sweden
- Charlotte Thålin
- Department of Clinical Sciences Karolinska Institute Danderyd Hospital Stockholm Sweden
- Max J Kellner
- Institute of Molecular Biotechnology of the Austrian Academy of Sciences Vienna Austria
- Wanda Christ
- Center for Infectious Medicine Department of Medicine Huddinge Karolinska Institutet Stockholm Sweden
- Sebastian Havervall
- Department of Clinical Sciences Karolinska Institute Danderyd Hospital Stockholm Sweden
- Stefan Mereiter
- Institute of Molecular Biotechnology of the Austrian Academy of Sciences Vienna Austria
- Sylvia Knapp
- Department of Medicine 1, Laboratory of Infection Biology Medical University of Vienna Vienna Austria
- Anna Sanchez Jimenez
- invIOs Vienna Austria
- Agnes Bugajska‐Schretter
- invIOs Vienna Austria
- Alexander Dohnal
- invIOs Vienna Austria
- Christine Ruf
- NBS‐C BioScience & Consulting GmbH Vienna Austria
- Romana Gugenberger
- invIOs Vienna Austria
- Astrid Hagelkruys
- Institute of Molecular Biotechnology of the Austrian Academy of Sciences Vienna Austria
- Nuria Montserrat
- Pluripotency for Organ Regeneration Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST) Barcelona Spain
- Ivona Kozieradzki
- Department of Medical Genetics, Life Sciences Institute University of British Columbia Vancouver Canada
- Omar Hasan Ali
- Department of Medical Genetics, Life Sciences Institute University of British Columbia Vancouver Canada
- Johannes Stadlmann
- Institute of Biochemistry, Department of Chemistry University of Natural resources and Life, Sciences (BOKU) Vienna Austria
- Michael R Holbrook
- NIAID Integrated Research Facility at Fort Detrick (IRF‐Frederick) Frederick Maryland USA
- Connie Schmaljohn
- NIAID Integrated Research Facility at Fort Detrick (IRF‐Frederick) Frederick Maryland USA
- Chris Oostenbrink
- Institute for Molecular Modeling and Simulation University of Natural Resources and Life Sciences (BOKU) Vienna Austria
- Robert H Shoemaker
- Chemopreventive Agent Development Research Group, Division of Cancer Prevention National Cancer Institute, National Institutes of Health Bethesda Maryland USA
- Ali Mirazimi
- Unit of Clinical Microbiology Karolinska Institutet and Karolinska University Hospital Stockholm Sweden
- Gerald Wirnsberger
- invIOs Vienna Austria
- Josef M Penninger
- Institute of Molecular Biotechnology of the Austrian Academy of Sciences Vienna Austria
- DOI
- https://doi.org/10.15252/emmm.202115230
- Journal volume & issue
-
Vol. 14,
no. 8
pp. n/a – n/a
Abstract
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.
Keywords