tetano
Editor, Senior Moderator
Commun Biol
. 2022 Nov 12;5(1):1237.
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[SUP] 1 2 [/SUP], Romina Bester[SUP] 3 [/SUP], Julia Sacherl[SUP] 3 [/SUP], Ramona Absmeier[SUP] 4 [/SUP], Carsten Peters[SUP] 4 [/SUP], Ulrike Protzer[SUP] 3 5 [/SUP], Carsten Brockmeyer[SUP] 6 7 [/SUP], Johannes Buchner[SUP] 8 [/SUP]
Affiliations
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.
. 2022 Nov 12;5(1):1237.
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[SUP] 1 2 [/SUP], Romina Bester[SUP] 3 [/SUP], Julia Sacherl[SUP] 3 [/SUP], Ramona Absmeier[SUP] 4 [/SUP], Carsten Peters[SUP] 4 [/SUP], Ulrike Protzer[SUP] 3 5 [/SUP], Carsten Brockmeyer[SUP] 6 7 [/SUP], Johannes Buchner[SUP] 8 [/SUP]
Affiliations
- PMID: 36371561
- DOI: 10.1038/s42003-022-04193-z
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.