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

Monteil V, Eaton B, Postnikova E, Murphy M, Braunsfeld B, Crozier I, Kricek F, Niederhöfer J, Schwarzböck A, Breid H, Devignot S, Klingström J, Thålin C, Kellner MJ, Christ W, Havervall S, Mereiter S, Knapp S, Sanchez Jimenez A, Bugajska-Schretter A, Dohnal A, Ruf C, Gugenberger R, Hagelkruys A, Montserrat N, Kozieradzki I, Hasan Ali O, Stadlmann J, Holbrook MR, Schmaljohn C, Oostenbrink C, Shoemaker RH, Mirazimi A, Wirnsberger G, Penninger JM

EMBO Mol Med 14 (8) e15230 [2022-08-08; online 2022-07-04]

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.

Category: Biochemistry

Category: Health

Type: Journal article

PubMed 35781796

DOI 10.15252/emmm.202115230

Crossref 10.15252/emmm.202115230

pmc: PMC9350269

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