Novel coronavirus-like particles targeting cells lining the respiratory tract

PLoS One. 2018 Sep 5;13(9):e0203489. doi: 10.1371/journal.pone.0203489. eCollection 2018.

Abstract

Virus like particles (VLPs) produced by the expression of viral structural proteins can serve as versatile nanovectors or potential vaccine candidates. In this study we describe for the first time the generation of HCoV-NL63 VLPs using baculovirus system. Major structural proteins of HCoV-NL63 have been expressed in tagged or native form, and their assembly to form VLPs was evaluated. Additionally, a novel procedure for chromatography purification of HCoV-NL63 VLPs was developed. Interestingly, we show that these nanoparticles may deliver cargo and selectively transduce cells expressing the ACE2 protein such as ciliated cells of the respiratory tract. Production of a specific delivery vector is a major challenge for research concerning targeting molecules. The obtained results show that HCoV-NL63 VLPs may be efficiently produced, purified, modified and serve as a delivery platform. This study constitutes an important basis for further development of a promising viral vector displaying narrow tissue tropism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Animals
  • Cell Line
  • Coronavirus NL63, Human*
  • Drug Delivery Systems / methods*
  • Humans
  • Macaca mulatta
  • Nanoparticles / chemistry*
  • Peptidyl-Dipeptidase A / pharmacology*
  • Respiratory Mucosa / cytology
  • Respiratory Mucosa / metabolism*
  • Spodoptera
  • Vaccines, Virus-Like Particle* / chemistry
  • Vaccines, Virus-Like Particle* / isolation & purification
  • Vaccines, Virus-Like Particle* / pharmacology

Substances

  • Vaccines, Virus-Like Particle
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2

Grants and funding

This work was supported by the National Science Center in Poland within the FUGA grant (UMO-2013/08/S/NZ6/00730) and Sonata Bis grant (UMO-2012/07/E/NZ6/01712), https://www.ncn.gov.pl/. Part of the work was also supported by the National Centre for Research and Development, Poland (Lider/27/55/L-2/10/2011), http://www.ncbr.gov.pl/. The Faculty of Biochemistry, Biophysics and Biotechnology of the Jagiellonian University is a beneficiary of the structural funds from the European Union (grant No: POIG.02.01.00-12-064/08—“Molecular biotechnology for health”). Faculty of Biochemistry, Biophysics and Biotechnology of the Jagiellonian University is a partner of the Leading National Research Center supported by the Ministry of Science and Higher Education of the Republic of Poland. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.