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Clinical grade ACE2 as a universal agent to block SARS-CoV-2 variants.
Monteil, Vanessa; Eaton, Brett; Postnikova, Elena; Murphy, Michael; Braunsfeld, Benedict; Crozier, Ian; Kricek, Franz; Niederhöfer, Janine; Schwarzböck, Alice; Breid, Helene; Devignot, Stephanie; Klingström, Jonas; Thålin, Charlotte; Kellner, Max J; Christ, Wanda; Havervall, Sebastian; Mereiter, Stefan; Knapp, Sylvia; Sanchez Jimenez, Anna; Bugajska-Schretter, Agnes; Dohnal, Alexander; Ruf, Christine; Gugenberger, Romana; Hagelkruys, Astrid; Montserrat, Nuria; Kozieradzki, Ivona; Hasan Ali, Omar; Stadlmann, Johannes; Holbrook, Michael R; Schmaljohn, Connie; Oostenbrink, Chris; Shoemaker, Robert H; Mirazimi, Ali; Wirnsberger, Gerald; Penninger, Josef M.
  • Monteil V; Unit of Clinical Microbiology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
  • Eaton B; NIAID Integrated Research Facility at Fort Detrick (IRF-Frederick), Frederick, Maryland, USA.
  • Postnikova E; NIAID Integrated Research Facility at Fort Detrick (IRF-Frederick), Frederick, Maryland, USA.
  • Murphy M; NIAID Integrated Research Facility at Fort Detrick (IRF-Frederick), Frederick, Maryland, USA.
  • Braunsfeld B; Institute for Molecular Modeling and Simulation, University of Natural Resources and Life Sciences (BOKU), Vienna, Austria.
  • Crozier I; Clinical Research Monitoring Program Directorate, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
  • Kricek F; NBS-C BioScience & Consulting GmbH, Vienna, Austria.
  • Niederhöfer J; invIOs, Vienna, Austria.
  • Schwarzböck A; invIOs, Vienna, Austria.
  • Breid H; invIOs, Vienna, Austria.
  • Devignot S; Unit of Clinical Microbiology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
  • Klingström J; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
  • Thålin C; Department of Clinical Sciences, Karolinska Institute Danderyd Hospital, Stockholm, Sweden.
  • Kellner MJ; Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria.
  • Christ W; Vienna BioCenter PhD Program, Doctoral School of the University at Vienna and Medical, University of Vienna, Vienna, Austria.
  • Havervall S; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
  • Mereiter S; Department of Clinical Sciences, Karolinska Institute Danderyd Hospital, Stockholm, Sweden.
  • Knapp S; Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria.
  • Sanchez Jimenez A; Department of Medicine 1, Laboratory of Infection Biology, Medical University of Vienna, Vienna, Austria.
  • Bugajska-Schretter A; invIOs, Vienna, Austria.
  • Dohnal A; invIOs, Vienna, Austria.
  • Ruf C; invIOs, Vienna, Austria.
  • Gugenberger R; NBS-C BioScience & Consulting GmbH, Vienna, Austria.
  • Hagelkruys A; invIOs, Vienna, Austria.
  • Montserrat N; Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria.
  • Kozieradzki I; Pluripotency for Organ Regeneration, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
  • Hasan Ali O; Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain.
  • Stadlmann J; Department of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver, Canada.
  • Holbrook MR; Department of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver, Canada.
  • Schmaljohn C; Institute of Biochemistry, Department of Chemistry, University of Natural resources and Life, Sciences (BOKU), Vienna, Austria.
  • Oostenbrink C; NIAID Integrated Research Facility at Fort Detrick (IRF-Frederick), Frederick, Maryland, USA.
  • Shoemaker RH; NIAID Integrated Research Facility at Fort Detrick (IRF-Frederick), Frederick, Maryland, USA.
  • Mirazimi A; Institute for Molecular Modeling and Simulation, University of Natural Resources and Life Sciences (BOKU), Vienna, Austria.
  • Wirnsberger G; Chemopreventive Agent Development Research Group, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
  • Penninger JM; Unit of Clinical Microbiology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
EMBO Mol Med ; 14(8): e15230, 2022 08 08.
Article in English | MEDLINE | ID: covidwho-1918173
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Angiotensin-Converting Enzyme 2 / COVID-19 Drug Treatment Type of study: Prognostic study Topics: Vaccines / Variants Limits: Humans Language: English Journal: EMBO Mol Med Journal subject: Molecular Biology Year: 2022 Document Type: Article Affiliation country: Emmm.202115230

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Angiotensin-Converting Enzyme 2 / COVID-19 Drug Treatment Type of study: Prognostic study Topics: Vaccines / Variants Limits: Humans Language: English Journal: EMBO Mol Med Journal subject: Molecular Biology Year: 2022 Document Type: Article Affiliation country: Emmm.202115230