Open AccessClinical grade ACE2 as a universal agent to block SARS‐CoV ‐2 variants
Author(s) -
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,
BugajskaSchretter 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
Publication year - 2022
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.202115230
Subject(s) - covid-19 , recombinant dna , potency , virology , antibody , neutralizing antibody , chemistry , microbiology and biotechnology , biology , immunology , virus , medicine , gene , biochemistry , in vitro , disease , pathology , infectious disease (medical specialty) , outbreak
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.