EMBO Molecular Medicine (Jul 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
- Brett Eaton
- NIAID Integrated Research Facility at Fort Detrick (IRF‐Frederick)
- Elena Postnikova
- NIAID Integrated Research Facility at Fort Detrick (IRF‐Frederick)
- Michael Murphy
- NIAID Integrated Research Facility at Fort Detrick (IRF‐Frederick)
- Benedict Braunsfeld
- Institute for Molecular Modeling and Simulation, University of Natural Resources and Life Sciences (BOKU)
- Ian Crozier
- Clinical Research Monitoring Program Directorate, Frederick National Laboratory for Cancer Research
- Franz Kricek
- NBS‐C BioScience & Consulting GmbH
- Janine Niederhöfer
- invIOs
- Alice Schwarzböck
- invIOs
- Helene Breid
- invIOs
- Stephanie Devignot
- Unit of Clinical Microbiology, Karolinska Institutet and Karolinska University Hospital
- Jonas Klingström
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet
- Charlotte Thålin
- Department of Clinical Sciences, Karolinska Institute Danderyd Hospital
- Max J Kellner
- Institute of Molecular Biotechnology of the Austrian Academy of Sciences
- Wanda Christ
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet
- Sebastian Havervall
- Department of Clinical Sciences, Karolinska Institute Danderyd Hospital
- Stefan Mereiter
- Institute of Molecular Biotechnology of the Austrian Academy of Sciences
- Sylvia Knapp
- Department of Medicine 1, Laboratory of Infection Biology, Medical University of Vienna
- Anna Sanchez Jimenez
- invIOs
- Agnes Bugajska‐Schretter
- invIOs
- Alexander Dohnal
- invIOs
- Christine Ruf
- NBS‐C BioScience & Consulting GmbH
- Romana Gugenberger
- invIOs
- Astrid Hagelkruys
- Institute of Molecular Biotechnology of the Austrian Academy of Sciences
- Nuria Montserrat
- Pluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST)
- Ivona Kozieradzki
- Department of Medical Genetics, Life Sciences Institute, University of British Columbia
- Omar Hasan Ali
- Department of Medical Genetics, Life Sciences Institute, University of British Columbia
- Johannes Stadlmann
- Institute of Biochemistry, Department of Chemistry, University of Natural resources and Life, Sciences (BOKU)
- Michael R Holbrook
- NIAID Integrated Research Facility at Fort Detrick (IRF‐Frederick)
- Connie Schmaljohn
- NIAID Integrated Research Facility at Fort Detrick (IRF‐Frederick)
- Chris Oostenbrink
- Institute for Molecular Modeling and Simulation, University of Natural Resources and Life Sciences (BOKU)
- Robert H Shoemaker
- Chemopreventive Agent Development Research Group, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health
- Ali Mirazimi
- Unit of Clinical Microbiology, Karolinska Institutet and Karolinska University Hospital
- Gerald Wirnsberger
- invIOs
- Josef M Penninger
- Institute of Molecular Biotechnology of the Austrian Academy of Sciences
- DOI
- https://doi.org/10.15252/emmm.202115230
- Journal volume & issue
-
Vol. 14,
no. 8
pp. 1 – 13
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
