PMID- 37001147 OWN - NLM STAT- MEDLINE DCOM- 20230509 LR - 20240210 IS - 1526-4602 (Electronic) IS - 1525-7797 (Linking) VI - 24 IP - 5 DP - 2023 May 8 TI - Biomimetic SARS-CoV-2 Spike Protein Nanoparticles. PG - 2030-2041 LID - 10.1021/acs.biomac.2c01465 [doi] AB - 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. FAU - Phan, Alvin AU - Phan A AD - Department of Pharmacology and Pharmaceutical Sciences, USC Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, 1985 Zonal Avenue, Los Angeles, California 90089, United States. FAU - Avila, Hugo AU - Avila H AUID- ORCID: 0000-0003-3742-589X AD - Department of Pharmacology and Pharmaceutical Sciences, USC Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, 1985 Zonal Avenue, Los Angeles, California 90089, United States. FAU - MacKay, J Andrew AU - MacKay JA AUID- ORCID: 0000-0002-3626-1654 AD - Department of Pharmacology and Pharmaceutical Sciences, USC Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, 1985 Zonal Avenue, Los Angeles, California 90089, United States. AD - Department of Ophthalmology, Keck School of Medicine of USC, University of Southern California, 1450 San Pablo Street, Los Angeles, California 90033, United States. AD - Alfred E. Mann Department of Biomedical Engineering, USC Viterbi School of Engineering, University of Southern California, 1042 Downey Way, Los Angeles, California 90089, United States. LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20230331 PL - United States TA - Biomacromolecules JT - Biomacromolecules JID - 100892849 RN - 0 (spike protein, SARS-CoV-2) RN - 0 (Spike Glycoprotein, Coronavirus) RN - 0 (Receptors, Virus) SB - IM MH - Humans MH - *COVID-19 MH - Spike Glycoprotein, Coronavirus/genetics/metabolism MH - SARS-CoV-2 MH - Receptors, Virus/chemistry/metabolism MH - Biomimetics MH - Protein Binding MH - *Nanoparticles EDAT- 2023/04/01 06:00 MHDA- 2023/05/09 10:16 CRDT- 2023/03/31 17:23 PHST- 2023/05/09 10:16 [medline] PHST- 2023/04/01 06:00 [pubmed] PHST- 2023/03/31 17:23 [entrez] AID - 10.1021/acs.biomac.2c01465 [doi] PST - ppublish SO - Biomacromolecules. 2023 May 8;24(5):2030-2041. doi: 10.1021/acs.biomac.2c01465. Epub 2023 Mar 31.