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Nat Nanotechnol. Phage capsid nanoparticles with defined ligand arrangement block influenza virus entry

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  • Nat Nanotechnol. Phage capsid nanoparticles with defined ligand arrangement block influenza virus entry


    Nat Nanotechnol. 2020 Mar 30. doi: 10.1038/s41565-020-0660-2. [Epub ahead of print]
    Phage capsid nanoparticles with defined ligand arrangement block influenza virus entry.


    Lauster D1,2, Klenk S3,4, Ludwig K5, Nojoumi S6,7, Behren S3,4, Adam L3,4, Stadtm?ller M8, Saenger S8, Zimmler S8, H?nzke K9, Yao L9, Hoffmann U10, Bardua M10, Hamann A10, Witzenrath M9, Sander LE9, Wolff T8, Hocke AC9, Hippenstiel S9, De Carlo S11, Neudecker J12, Osterrieder K13, Budisa N6,7, Netz RR14, B?ttcher C5, Liese S15,16, Herrmann A17, Hackenberger CPR18,19.

    Author information




    Abstract

    Multivalent interactions at biological interfaces occur frequently in nature and mediate recognition and interactions in essential physiological processes such as cell-to-cell adhesion. Multivalency is also a key principle that allows tight binding between pathogens and host cells during the initial stages of infection. One promising approach to prevent infection is the design of synthetic or semisynthetic multivalent binders that interfere with pathogen adhesion1-4. Here, we present a multivalent binder that is based on a spatially defined arrangement of ligands for the viral spike protein haemagglutinin of the influenza A virus. Complementary experimental and theoretical approaches demonstrate that bacteriophage capsids, which carry host cell haemagglutinin ligands in an arrangement matching the geometry of binding sites of the spike protein, can bind to viruses in a defined multivalent mode. These capsids cover the entire virus envelope, thus preventing its binding to the host cell as visualized by cryo-electron tomography. As a consequence, virus infection can be inhibited in vitro, ex vivo and in vivo. Such highly functionalized capsids present an alternative to strategies that target virus entry by spike-inhibiting antibodies5 and peptides6 or that address late steps of the viral replication cycle7.



    PMID:32231271DOI:10.1038/s41565-020-0660-2


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