论文标题
SARS-COV-2诱导的凋亡的单细胞数学模型和抗炎干预的影响
A single-cell mathematical model of SARS-CoV-2 induced pyroptosis and the effects of anti-inflammatory intervention
论文作者
论文摘要
凋亡是一种细胞死亡的炎症模式，可以导致与2019年冠状病毒病例有关的细胞因子风暴（Covid-19）。 NLRP3炎性体的形成是凋亡的核心，可能是由严重的急性呼吸综合症冠状病毒2（SARS-COV-2）诱导的。某些抗炎药可以抑制炎性体的形成和扩展的凋亡。在这项研究中，我们提出了一种单细胞数学模型，该模型捕获了NLRP3炎性体，凋亡细胞死亡的形成以及对抗炎干预的反应，从而阻碍了NLRP3炎症体的形成。该模型是根据一个普通微分方程（ODE）的系统制定的，该系统描述了涉及流凋亡的生物成分的动力学。我们的结果表明，抗炎药可以延迟NLRP3炎症体的形成，因此可能会改变细胞死亡的模式，从炎症（凋亡）变为非炎症，例如凋亡）。单细胞模型正在SARS-COV-2组织模拟器中实施，并与COVID-19的宿主 - 动力学中的多学科联盟合作。在本文中，我们提供了SARS-COV-2组织模拟器的概述，并强调了凋亡对细胞水平的影响。
Pyroptosis is an inflammatory mode of cell death that can contribute to the cytokine storm associated with severe cases of coronavirus disease 2019 (COVID-19). The formation of the NLRP3 inflammasome is central to pyroptosis, which may be induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Inflammasome formation, and by extension pyroptosis, may be inhibited by certain anti-inflammatory drugs. In this study, we present a single-cell mathematical model that captures the formation of the NLRP3 inflammasome, pyroptotic cell death and responses to anti-inflammatory intervention that hinder the formation of the NLRP3 inflammasome. The model is formulated in terms of a system of ordinary differential equations (ODEs) that describe the dynamics of the biological components involved in pyroptosis. Our results demonstrate that an anti-inflammatory drug can delay the formation of the NLRP3 inflammasome, and thus may alter the mode of cell death from inflammatory (pyroptosis) to non-inflammatory e.g., apoptosis). The single-cell model is being implemented in a SARS-CoV-2 Tissue Simulator, in collaboration with a multidisciplinary coalition investigating within host-dynamics of COVID-19. In this paper, we provide an overview of the SARS-CoV-2 Tissue Simulator and highlight the effects of pyroptosis on a cellular level.
