PuSH - Publikationsserver des Helmholtz Zentrums München: Multimeric ACE2-IgM fusions as broadly active antivirals that potently neutralize SARS-CoV-2 variants.

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Svilenov, H.L.* ; Bester, R. ; Sacherl, J. ; Absmeier, R.* ; Peters, C.* ; Protzer, U. ; Brockmeyer, C.* ; Buchner, J.*

Multimeric ACE2-IgM fusions as broadly active antivirals that potently neutralize SARS-CoV-2 variants.

Comm. Biol. 5:1237 (2022)

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Coronavirus infections are a world-wide threat to human health. A promising strategy to develop a broadly active antiviral is the use of fusion proteins consisting of an antibody IgG Fc region and a human ACE2 domain to which the viral spike proteins bind. Here we create antiviral fusion proteins based on IgM scaffolds. The hexameric ACE2-IgM-Fc fusions can be efficiently produced in mammalian cells and they neutralize the infectious virus with picomolar affinity thus surpassing monomeric ACE2-IgM-Fc by up to 96-fold in potency. In addition, the ACE2-IgM fusion shows increased neutralization efficiency for the highly infectious SARS-CoV-2 omicron variant in comparison to prototypic SARS-CoV-2. Taken together, these multimeric IgM fusions proteins are a powerful weapon to fight coronavirus infections.

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