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

Autor: Wirnsberger G; Apeiron Biologics, Vienna, Austria., Monteil V; Karolinska Institutet and Karolinska University Hospital, Unit of Clinical Microbiology, SE-17182, Stockholm, Sweden., Eaton B; NIAID Integrated Research Facility at Fort Detrick (IRF-Frederick), Frederick, MD 21702, USA., Postnikova E; NIAID Integrated Research Facility at Fort Detrick (IRF-Frederick), Frederick, MD 21702, USA., Murphy M; NIAID Integrated Research Facility at Fort Detrick (IRF-Frederick), Frederick, MD 21702, USA., Braunsfeld B; Institute for Molecular Modeling and Simulation, University of Natural Resources and Life Sciences (BOKU), Austria., Crozier I; NIAID Integrated Research Facility at Fort Detrick (IRF-Frederick), Frederick, MD 21702, USA., Kricek F; NBS-C BioScience & Consulting GmbH, Vienna, Austria., Niederhöfer J; Apeiron Biologics, Vienna, Austria., Schwarzböck A; Apeiron Biologics, Vienna, Austria., Breid H; Apeiron Biologics, Vienna, Austria., Jimenez AS; Apeiron Biologics, Vienna, Austria., Bugajska-Schretter A; Apeiron Biologics, Vienna, Austria., Dohnal A; Apeiron Biologics, Vienna, Austria., Ruf C; NBS-C BioScience & Consulting GmbH, Vienna, Austria., Gugenberger R; Apeiron Biologics, Vienna, Austria., Hagelkruys A; Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria., Montserrat N; 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., Holbrook MR; NIAID Integrated Research Facility at Fort Detrick (IRF-Frederick), Frederick, MD 21702, USA., Oostenbrink C; Institute for Molecular Modeling and Simulation, University of Natural Resources and Life Sciences (BOKU), Austria., Shoemaker RH; Chemopreventive Agent Development Research Group, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892., Mirazimi A; Karolinska Institutet and Karolinska University Hospital, Unit of Clinical Microbiology, SE-17182, Stockholm, Sweden., Penninger JM; Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria.; Department of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver, Canada.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2021 Sep 10. Date of Electronic Publication: 2021 Sep 10.
DOI: 10.1101/2021.09.10.459744
Abstrakt: The recent emergence of multiple SARS-CoV-2 variants has caused considerable concern due to 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, and Delta, 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 multiple 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.
Databáze: MEDLINE