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

Hristo L. Svilenov; Romina Bester; Julia Sacherl; Ramona Absmeier; Carsten Peters; Ulrike Protzer; Carsten Brockmeyer; Johannes Buchner

doi:10.1038/s42003-022-04193-z

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

Hristo L. Svilenov, Romina Bester, Julia Sacherl, Ramona Absmeier, Carsten Peters, Ulrike Protzer, Carsten Brockmeyer, Johannes Buchner

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

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.

Original language	English
Article number	1237
Journal	Communications Biology
Volume	5
Issue number	1
DOIs	https://doi.org/10.1038/s42003-022-04193-z
State	Published - Dec 2022

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abstract = "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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AU - Svilenov, Hristo L.

AU - Bester, Romina

AU - Sacherl, Julia

AU - Absmeier, Ramona

AU - Peters, Carsten

AU - Protzer, Ulrike

AU - Brockmeyer, Carsten

AU - Buchner, Johannes

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

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