Pramanik Avijit, Mayer Justin, Sinha Sudarson Sekhar, Sharma Poonam C, Patibandla Shamily, Gao Ye, Corby Lauren R, Bates John T, Bierdeman Michael A, Tandon Ritesh, Seshadri Ram, Ray Paresh Chandra
Department of Chemistry and Biochemistry, Jackson State University, Jackson, Mississippi 39217, United States.
Materials Department, University of California, Santa Barbara, California 93106-5121, United States.
ACS Appl Bio Mater. 2022 Sep 2. doi: 10.1021/acsabm.2c00573.
The emergence of Alpha, Beta, Gamma, Delta, and Omicron variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for several million deaths up to now. Because of the huge amount of vaccine escape mutations in the spike (S) protein for different variants, the design of material for combating SARS-CoV-2 is very important for our society. Herein, we report on the design of a human angiotensin converting enzyme 2 (ACE2) peptide-conjugated plasmonic-magnetic heterostructure, which has the capability for magnetic separation, identification via surface enhanced Raman spectroscopy (SERS), and inhibition of different variant SARS-CoV-2 infections. In this work, plasmonic-magnetic heterostructures were developed using the initial synthesis of polyethylenimine (PEI)-coated FeO-based magnetic nanoparticles, and then gold nanoparticles (GNPs) were grown onto the surface of the magnetic nanoparticles. Experimental binding data between ACE2-conjugated plasmonic-magnetic heterostructures and spike-receptor-binding domain (RBD) show that the Omicron variant has maximum binding ability, and it follows Alpha < Beta < Gamma < Delta < Omicron. Our finding shows that, due to the high magnetic moment (specific magnetization 40 emu/g), bioconjugated heterostructures are capable of effective magnetic separation of pseudotyped SARS-CoV-2 bearing the Delta variant spike from an infected artificial nasal mucus fluid sample using a simple bar magnet. Experimental data show that due to the formation of huge "hot spots" in the presence of SARS-CoV-2, Raman intensity for the 4-aminothiolphenol (4-ATP) Raman reporter was enhanced sharply, which has been used for the identification of separated virus. Theoretical calculations using finite-difference time-domain (FDTD) simulation indicate that, due to the "hot spots" formation, a six orders of magnitude Raman enhancement can be observed. A concentration-dependent inhibition efficiency investigation using a HEK293T-human cell line indicates that ACE2 peptide-conjugated plasmonic-magnetic heterostructures have the capability of complete inhibition of entry of different variants and original SARS-CoV-2 pseudovirions into host cells.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的阿尔法、贝塔、伽马、德尔塔和奥密克戎变体的出现，迄今已导致数百万人死亡。由于不同变体的刺突（S）蛋白中存在大量疫苗逃逸突变，设计对抗SARS-CoV-2的材料对我们的社会非常重要。在此，我们报告了一种人血管紧张素转换酶2（ACE2）肽共轭的等离子体-磁性异质结构的设计，该结构具有磁分离能力、通过表面增强拉曼光谱（SERS）进行识别以及抑制不同变体SARS-CoV-2感染的能力。在这项工作中，通过最初合成聚乙烯亚胺（PEI）包覆的基于FeO的磁性纳米颗粒来制备等离子体-磁性异质结构，然后在磁性纳米颗粒表面生长金纳米颗粒（GNP）。ACE2共轭等离子体-磁性异质结构与刺突受体结合域（RBD）之间的实验结合数据表明，奥密克戎变体具有最大结合能力，其次序为阿尔法<贝塔<伽马<德尔塔<奥密克戎。我们的研究结果表明，由于高磁矩（比磁化强度为40 emu/g），生物共轭异质结构能够使用简单的条形磁铁从感染的人工鼻粘液样本中有效地磁分离携带德尔塔变体刺突的假型SARS-CoV-2。实验数据表明，由于在存在SARS-CoV-2的情况下形成了巨大的“热点”，4-氨基硫酚（4-ATP）拉曼报告分子的拉曼强度急剧增强，这已被用于识别分离出的病毒。使用时域有限差分（FDTD）模拟的理论计算表明，由于“热点”的形成，可以观察到六个数量级的拉曼增强。使用HEK293T人细胞系进行的浓度依赖性抑制效率研究表明，ACE2肽共轭的等离子体-磁性异质结构具有完全抑制不同变体和原始SARS-CoV-2假病毒颗粒进入宿主细胞的能力。
