Biomimetic SARS-CoV-2 Spike Protein Nanoparticles

被引：4

作者：

Phan, Alvin ^{[1
]}

Avila, Hugo ^{[1
]}

MacKay, J. Andrew ^{[1
,2
,3
]}

机构：

[1] Univ Southern Calif, USC Alfred E Mann Sch Pharm & Pharmaceut Sci, Dept Pharmacol & Pharmaceut Sci, Los Angeles, CA 90089 USA

[2] Univ Southern Calif, Keck Sch Med USC, Dept Ophthalmol, Los Angeles, CA 90033 USA

[3] Univ Southern Calif, USC Viterbi Sch Engn, Alfred E Mann Dept Biomed Engn, Los Angeles, CA 90089 USA

来源：

BIOMACROMOLECULES | 2023年 / 24卷 / 05期

基金：

美国国家卫生研究院;

关键词：

ENTRY; ACE2; MECHANISMS; EXPRESSION; TMPRSS2; DESIGN; FUSION; CELLS;

D O I：

10.1021/acs.biomac.2c01465

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：2030 / 2041

页数：12

共 54 条

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