Phage capsid nanoparticles with defined ligand arrangement block influenza virus entry

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

27 Scopus Citations
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Author(s)

  • Daniel Lauster
  • Simon Klenk
  • Kai Ludwig
  • Saba Nojoumi
  • Sandra Behren
  • Lutz Adam
  • Marlena Stadtmüller
  • Sandra Saenger
  • Stephanie Zimmler
  • Katja Hönzke
  • Ling Yao
  • Ute Hoffmann
  • Markus Bardua
  • Alf Hamann
  • Martin Witzenrath
  • Leif E. Sander
  • Thorsten Wolff
  • Andreas C. Hocke
  • Stefan Hippenstiel
  • Sacha De Carlo
  • Jens Neudecker
  • Nediljko Budisa
  • Roland R. Netz
  • Christoph Böttcher
  • Susanne Liese
  • Andreas Herrmann
  • Christian P. R. Hackenberger

Detail(s)

Original languageEnglish
Pages (from-to)373-379
Journal / PublicationNature Nanotechnology
Volume15
Issue number5
Online published30 Mar 2020
Publication statusPublished - May 2020
Externally publishedYes

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.

Citation Format(s)

Phage capsid nanoparticles with defined ligand arrangement block influenza virus entry. / Lauster, Daniel; Klenk, Simon; Ludwig, Kai; Nojoumi, Saba; Behren, Sandra; Adam, Lutz; Stadtmüller, Marlena; Saenger, Sandra; Zimmler, Stephanie; Hönzke, Katja; Yao, Ling; Hoffmann, Ute; Bardua, Markus; Hamann, Alf; Witzenrath, Martin; Sander, Leif E.; Wolff, Thorsten; Hocke, Andreas C.; Hippenstiel, Stefan; De Carlo, Sacha; Neudecker, Jens; Osterrieder, Klaus; Budisa, Nediljko; Netz, Roland R.; Böttcher, Christoph; Liese, Susanne; Herrmann, Andreas; Hackenberger, Christian P. R.

In: Nature Nanotechnology, Vol. 15, No. 5, 05.2020, p. 373-379.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review