McColman Sarah, Shkalla Klaidi, Sidhu Pavleen, Liang Jady, Osman Selena, Kovacs Norbert, Bokhari Zainab, Forjaz Marques Ana Carolina, Li Yuchong, Lin Qiwen, Zhang Haibo, Cramb David T
Department of Chemistry and Biology, Faculty of Science, Toronto Metropolitan University Toronto ON Canada
Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Unity Health Toronto Toronto ON Canada.
Nanoscale Adv. 2023 Jul 14;5(16):4167-4181. doi: 10.1039/d3na00190c. eCollection 2023 Aug 8.
The SARS-CoV-2 virus, implicated in the COVID-19 pandemic, recognizes and binds host cells using its spike glycoprotein through an angiotensin converting enzyme 2 (ACE-2) receptor-mediated pathway. Recent research suggests that spatial distributions of the spike protein may influence viral interactions with target cells and immune systems. The goal of this study has been to develop a liposome-based virus-like particle (VLP) by reconstituting the SARS-CoV-2 spike glycoprotein within a synthetic nanoparticle membrane, aiming to eventually establish tunability in spike protein presentation on the nanoparticle surface. Here we report on first steps to this goal, wherein liposomal SARS-CoV-2 VLPs were successfully produced detergent mediated spike protein reconstitution. The resultant VLPs are shown to successfully co-localize with the ACE-2 receptor on lung epithelial cell surfaces, followed by internalization into these cells. These VLPs are the first step toward the overall goal of this research which is to form an understanding of the relationship between spike protein surface density and cell-level immune response, eventually toward creating better vaccines and anti-viral therapeutics.
引发新冠疫情的严重急性呼吸综合征冠状病毒2(SARS-CoV-2)病毒,通过血管紧张素转换酶2(ACE-2)受体介导的途径,利用其刺突糖蛋白识别并结合宿主细胞。近期研究表明,刺突蛋白的空间分布可能会影响病毒与靶细胞及免疫系统的相互作用。本研究的目标是通过在合成纳米颗粒膜内重组SARS-CoV-2刺突糖蛋白,开发一种基于脂质体的病毒样颗粒(VLP),最终目标是在纳米颗粒表面实现刺突蛋白呈现的可调控性。在此,我们报告实现这一目标的初步步骤,即通过去污剂介导的刺突蛋白重组成功制备了脂质体SARS-CoV-2病毒样颗粒。结果表明,所得病毒样颗粒成功地与肺上皮细胞表面的ACE-2受体共定位,随后被这些细胞内化。这些病毒样颗粒是本研究总体目标的第一步,该目标是了解刺突蛋白表面密度与细胞水平免疫反应之间的关系,最终开发出更好的疫苗和抗病毒疗法。