Issue 47, 2021

Bacteriophage PRD1 as a nanoscaffold for drug loading


Viruses are very attractive biomaterials owing to their capability as nanocarriers of genetic material. Efforts have been made to functionalize self-assembling viral protein capsids on their exterior or interior to selectively take up different payloads. PRD1 is a double-stranded DNA bacteriophage comprising an icosahedral protein outer capsid and an inner lipidic vesicle. Here, we report the three-dimensional structure of PRD1 in complex with the antipsychotic drug chlorpromazine (CPZ) by cryo-electron microscopy. We show that the jellyrolls of the viral major capsid protein P3, protruding outwards from the capsid shell, serve as scaffolds for loading heterocyclic CPZ molecules. Additional X-ray studies and molecular dynamics simulations show the binding modes and organization of CPZ molecules when complexed with P3 only and onto the virion surface. Collectively, we provide a proof of concept for the possible use of the lattice-like organisation and the quasi-symmetric morphology of virus capsomers for loading heterocyclic drugs with defined properties.

Graphical abstract: Bacteriophage PRD1 as a nanoscaffold for drug loading

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Article information

Article type
27 Jun 2021
06 Nov 2021
First published
01 Dec 2021
This article is Open Access
Creative Commons BY license

Nanoscale, 2021,13, 19875-19883

Bacteriophage PRD1 as a nanoscaffold for drug loading

H. M. E. Duyvesteyn, I. Santos-Pérez, F. Peccati, A. Martinez-Castillo, T. S. Walter, D. Reguera, F. M. Goñi, G. Jiménez-Osés, H. M. Oksanen, D. I. Stuart and N. G. A. Abrescia, Nanoscale, 2021, 13, 19875 DOI: 10.1039/D1NR04153C

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