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

Autor: 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
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: EMBO Molecular Medicine, Vol 14, Iss 8, Pp 1-13 (2022)
Druh dokumentu: article
ISSN: 1757-4676
1757-4684
DOI: 10.15252/emmm.202115230
Popis: 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.
Databáze: Directory of Open Access Journals
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