journal article·2021Open access

Bacteriophage PRD1 as a nanoscaffold for drug loading

Helen M. E. Duyvesteyn, Isaac Santos-Pérez, Francesca Peccati, Ane Martinez-Castillo, Thomas S. Walter, David Reguera, Felix M. Goñi, Gonzalo Jiménez-Osés, Hanna M. Oksanen, David I. Stuart, Nicola G. A. Abrescia

Nanoscale· Volume 13· Issue 47

Abstract

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.
Source: openalex_inverted_index · Quality: candidate unverified · Source record ↗

Research context

OpenAlex topics: Bacteriophages and microbial interactions · RNA and protein synthesis mechanisms · Bacterial Genetics and Biotechnology

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Division of Structural Biology, University of Oxford, The Henry Wellcome Building for Genomic Medicine, Headington, Oxford, UK

Diamond Light Source, Harwell Science and Innovation Campus, Didcot, UK

Structure and Cell Biology of Viruses Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, Spain

Computational Chemistry Lab, CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Derio, Spain

Departament de Física de la Matèria Condensada, Facultat de Física, Universitat de Barcelona, Barcelona, Spain

Departamento de Bioquímica, University of the Basque Country (UPV/EHU) and Instituto Biofisika (CSIC, UPV/EHU), Leioa, Spain

IKERBASQUE, Basque Foundation for Science, Bilbao, Spain

Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, Viikki Biocenter, University of Helsinki, Helsinki, Finland

Instruct-ERIC, Oxford House, Parkway Court, John Smith Drive, Oxford, UK

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain

Funding

Hezkuntza, Hizkuntza Politika Eta Kultura Saila, Eusko Jaurlaritza · NIHR Oxford Biomedical Research Centre · Helsingin Yliopisto · Academy of Finland · Wellcome Trust · Medical Research Council · Ministerio de Economía y Competitividad

References (39)

Show source-provided references
1. Chung · Adv. Drug Delivery Rev. · 2020 · 156 · 21410.1016/j.addr.2020.06.024 ↗
2. Li · Nat. Rev. Genet. · 2020 · 21 · 25510.1038/s41576-019-0205-4 ↗
3. Yanez-Munoz · Nat. Med. · 2006 · 12 · 34810.1038/nm1365 ↗
4. Steinmetz · Nanomedicine · 2011 · 6 · 35110.2217/nnm.10.136 ↗
5. de la Escosura · J. Mater. Chem. · 2009 · 19 · 227410.1039/b815274h ↗
6. Ma · Adv. Drug Delivery Rev. · 2012 · 64 · 81110.1016/j.addr.2012.01.005 ↗
7. Karimi · Adv. Drug Delivery Rev. · 2016 · 106 · 4510.1016/j.addr.2016.03.003 ↗
8. Young · Annu. Rev. Phytopathol. · 2008 · 46 · 36110.1146/annurev.phyto.032508.131939 ↗
9. Sunderland · Angew. Chem., Int. Ed. · 2017 · 56 · 196410.1002/anie.201606181 ↗
10. Berardi · Nanoscale · 2018 · 10 · 166710.1039/C7NR07182E ↗
11. Abrescia · Annu. Rev. Biochem. · 2012 · 81 · 79510.1146/annurev-biochem-060910-095130 ↗
12. Oksanen · Adv. Exp. Med. Biol. · 2019 · 1215 · 8510.1007/978-3-030-14741-9_5 ↗
13. Abrescia · Nature · 2004 · 432 · 6810.1038/nature03056 ↗
14. Cockburn · Nature · 2004 · 432 · 12210.1038/nature03053 ↗
15. Peralta · PLos Biol. · 2013 · 11 · e100166710.1371/journal.pbio.1001667 ↗
16. Hong · PLos Biol. · 2014 · 12 · e100202410.1371/journal.pbio.1002024 ↗
17. Santos-Pérez · Biochim. Biophys. Acta, Gen. Subj. · 2017 · 1861 · 66410.1016/j.bbagen.2016.12.013 ↗
18. Ahyayauch · J. Liposome Res. · 2003 · 13 · 14710.1081/LPR-120020317 ↗
19. Ahyayauch · Therapie · 1999 · 54 · 585
20. Jutila · Chem. Phys. Lipids · 2001 · 112 · 15110.1016/S0009-3084(01)00175-X ↗
21. Wajnberg · Biochim. Biophys. Acta · 1988 · 944 · 18510.1016/0005-2736(88)90431-2 ↗
22. Saito · Langmuir · 2000 · 16 · 639110.1021/la991297l ↗
23. Li · Curr. Top. Med. Chem. · 2016 · 16 · 338510.2174/1568026616666160608084834 ↗
24. Morgan · Biomed. Pharmacother. · 2019 · 111 · 140810.1016/j.biopha.2019.01.020 ↗
25. Mosnaim · Am. J. Ther. · 2006 · 13 · 26110.1097/01.mjt.0000212897.20458.63 ↗
26. Benson · Cell · 1999 · 98 · 82510.1016/S0092-8674(00)81516-0 ↗
27. Wilder · Int. J. High Throughput Screening · 2010 · 2010 · 109
28. Nishi · J. Biol. Chem. · 2011 · 286 · 1442710.1074/jbc.M110.208926 ↗
29. Nys · Proc. Natl. Acad. Sci. U. S. A. · 2016 · 113 · E669610.1073/pnas.1603101113 ↗
30. McDowell · Acta Crystallogr., Sect. B: Struct. Crystallogr. Cryst. Chem. · 1969 · B25 · 217510.1107/S0567740869005437 ↗
31. Obata · Acta Crystallogr., Sect. C: Cryst. Struct. Commun. · 1984 · C40 · 4510.1107/S0108270184002961 ↗
32. Attwood · Magn. Reson. Chem. · 1994 · 32 · 46810.1002/mrc.1260320807 ↗
33. Benson · Acta Crystallogr., Sect. D: Biol. Crystallogr. · 2002 · 58 · 3910.1107/S0907444901017279 ↗
34. Rub · J. Ind. Eng. Chem. · 2014 · 20 · 202310.1016/j.jiec.2013.09.027 ↗
35. Azinas · Nanoscale · 2018 · 10 · 776910.1039/C8NR00196K ↗
36. Loo · J. Am. Chem. Soc. · 2017 · 129 · 1111110.1021/ja071896b ↗
37. Yildiz · J. Controlled Release · 2013 · 172 · 56810.1016/j.jconrel.2013.04.023 ↗
38. Ravantti · Viruses · 2020 · 12 · 114610.3390/v12101146 ↗
39. Pettersen · J. Comput. Chem. · 2004 · 25 · 160510.1002/jcc.20084 ↗