关键词: COVID-19 SARS-CoV-2 cell membrane vesicle cytokine storm nanodecoy

Mesh : Angiotensin-Converting Enzyme 2 Animals Betacoronavirus COVID-19 Cell Membrane / chemistry Coronavirus Infections / therapy Cytokines / antagonists & inhibitors Granulocyte-Macrophage Colony-Stimulating Factor / antagonists & inhibitors HEK293 Cells Humans Interleukin-6 / antagonists & inhibitors Mice Mice, Inbred ICR Monocytes Nanoparticles / chemistry therapeutic use Pandemics Peptidyl-Dipeptidase A / metabolism Pneumonia, Viral / therapy Receptors, Cytokine / metabolism SARS-CoV-2 THP-1 Cells Virus Internalization / drug effects

来  源:   DOI:10.1073/pnas.2014352117   PDF(Sci-hub)   PDF(Pubmed)

Abstract:
The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has highlighted the urgent need to rapidly develop therapeutic strategies for such emerging viruses without effective vaccines or drugs. Here, we report a decoy nanoparticle against COVID-19 through a powerful two-step neutralization approach: virus neutralization in the first step followed by cytokine neutralization in the second step. The nanodecoy, made by fusing cellular membrane nanovesicles derived from human monocytes and genetically engineered cells stably expressing angiotensin converting enzyme II (ACE2) receptors, possesses an antigenic exterior the same as source cells. By competing with host cells for virus binding, these nanodecoys effectively protect host cells from the infection of pseudoviruses and authentic SARS-CoV-2. Moreover, relying on abundant cytokine receptors on the surface, the nanodecoys efficiently bind and neutralize inflammatory cytokines including interleukin 6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF), and significantly suppress immune disorder and lung injury in an acute pneumonia mouse model. Our work presents a simple, safe, and robust antiviral nanotechnology for ongoing COVID-19 and future potential epidemics.
摘要:
COVID-19大流行,由严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引起,强调迫切需要在没有有效疫苗或药物的情况下迅速开发针对此类新兴病毒的治疗策略。这里,我们报道了一种针对COVID-19的诱骗纳米颗粒,该纳米颗粒通过强大的两步中和方法:第一步中和病毒,然后第二步中和细胞因子.纳米诱饵,通过融合来自人单核细胞的细胞膜纳米囊泡和稳定表达血管紧张素转换酶II(ACE2)受体的基因工程细胞,具有与来源细胞相同的抗原外观。通过与宿主细胞竞争病毒结合,这些纳米诱饵有效地保护宿主细胞免受假病毒和真正的SARS-CoV-2的感染。此外,依赖于表面上丰富的细胞因子受体,纳米诱饵有效地结合和中和炎症细胞因子,包括白细胞介素6(IL-6)和粒细胞-巨噬细胞集落刺激因子(GM-CSF),并显著抑制急性肺炎小鼠模型的免疫紊乱和肺损伤。我们的工作提出了一个简单的,安全,以及针对正在进行的COVID-19和未来潜在流行病的强大抗病毒纳米技术。
公众号