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Multivalent Peptide–Nanoparticle Conjugates for Influenza-Virus Inhibition |
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| Authors: | Daniel Lauster Maria Glanz Markus Bardua Dr Kai Ludwig Dr Markus Hellmund Dr Ute Hoffmann Prof?Dr Alf Hamann Dr Christoph Böttcher Prof?Dr Rainer Haag Prof?Dr Christian P R Hackenberger Prof?Dr Andreas Herrmann |
| Institution: | 1. Institut für Biologie, Molekulare Biophysik, IRI Life Sciences, Humboldt-Universität zu Berlin, Invalidenstrasse 42, 10115 Berlin, Germany
These authors contributed equally to this work.;2. Leibniz-Institut für Molekulare Pharmakologie (FMP), Robert-Rössle-Strasse-10, 13125 Berlin, Germany Humboldt Universität zu Berlin, Institut für Chemie, Brook-Taylor-Strasse 2, 12489 Berlin, Germany These authors contributed equally to this work.;3. Therapeutische Genregulation und Experimentelle Rheumatologie, Deutsches Rheuma-Forschungszentrum Berlin, Charité 14, Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany;4. Forschungszentrum für Elektronenmikroskopie and Core Facility BioSupraMol, Institut für Chemie und Biochemie, Freie Universität Berlin, Fabeckstrasse 36a, 14195 Berlin, Germany;5. Institut für Chemie und Biochemie—Organische Chemie, Freie Universität Berlin, Takustrasse 3, 14195 Berlin, Germany;6. Leibniz-Institut für Molekulare Pharmakologie (FMP), Robert-Rössle-Strasse-10, 13125 Berlin, Germany;7. Institut für Biologie, Molekulare Biophysik, IRI Life Sciences, Humboldt-Universität zu Berlin, Invalidenstrasse 42, 10115 Berlin, Germany |
| Abstract: | To inhibit binding of the influenza A virus to the host cell glycocalyx, we generate multivalent peptide–polymer nanoparticles binding with nanomolar affinity to the virus via its spike protein hemagglutinin. The chosen dendritic polyglycerol scaffolds are highly biocompatible and well suited for a multivalent presentation. We could demonstrate in vitro that by increasing the size of the polymer scaffold and adjusting the peptide density, viral infection is drastically reduced. Such a peptide–polymer conjugate qualified also in an in vivo infection scenario. With this study we introduce the first non-carbohydrate-based, covalently linked, multivalent virus inhibitor in the nano- to picomolar range by ensuring low peptide-ligand density on a larger dendritic scaffold. |
| Keywords: | antiviral agents in vivo studies influenza virus multivalency peptides |