Biomimetic SARS-CoV-2 Spike Protein Nanoparticles.
Alvin PhanHugo AvilaJohn Andrew MacKayPublished in: Biomacromolecules (2023)
COVID-19 is an infectious respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus contains a crucial coat protein that engages with target cells via a receptor binding domain (RBD) on its spike protein. To better study the RBD and its therapeutic opportunities, we genetically engineered a simple fusion with a thermo-responsive elastin-like polypeptide (ELP). These fusions express in Escherichia coli at a high yield in the soluble fraction and were easily purified using ELP-mediated phase separation (79 mg/L culture). Interestingly, they assembled peptide-based nanoparticles ( R h = 71.4 nm), which was attributed to oligomerization of RBDs (25.3 kDa) counterbalanced by steric stabilization by a soluble ELP (73.4 kDa). To investigate their biophysical properties, we explored the size, shape, and binding affinity for the human angiotensin-converting enzyme 2 (hACE2) and cellular uptake. Biomimetic nanoparticles such as these may enable future strategies to target the same cells, tissues, and cell-surface receptors as those harnessed by SARS-CoV-2.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- induced apoptosis
- binding protein
- escherichia coli
- coronavirus disease
- angiotensin converting enzyme
- cell cycle arrest
- cell surface
- protein protein
- amino acid
- endothelial cells
- cell death
- heat shock protein
- signaling pathway
- endoplasmic reticulum stress
- staphylococcus aureus
- walled carbon nanotubes
- mass spectrometry
- cancer therapy
- induced pluripotent stem cells
- pseudomonas aeruginosa
- cystic fibrosis
- klebsiella pneumoniae
- biofilm formation
- transcription factor
- drug delivery