论文标题
建模SARS-COV-2感染对肾素 - 血管紧张素系统的分子影响
Modeling the molecular impact of SARS-CoV-2 infection on the renin-angiotensin system
论文作者
论文摘要
SARS-COV-2冠状病毒感染是由其峰值蛋白与血管紧张素转换酶2（ACE2）的结合介导的，该酶在肾素 - 血管紧张素系统（RAS）中起关键作用。 SARS-COV-2感染引起的RAS失调的研究对于更好地理解与Covid-19冠状病毒疾病相关的致病机制和危险因素以及设计有效的治疗策略至关重要。在这种情况下，我们基于有关蛋白质和肽浓度的数据开发了RAS的数学模型。该模型对来自健康正常和高血压个体的临床数据进行了测试。然后，我们使用我们的模型来分析SARS-COV-2感染对RA的影响，我们通过ACE2的下调作为病毒载荷的函数进行了建模。我们还使用它来预测靶向RAS靶向药物的影响，例如RAS-BLOCKER，人重组ACE2和血管紧张素1-7肽对Covid-19患者的影响；该模型预测了某些药物的临床结果会有所改善，而其他药物则会恶化。
SARS-CoV-2 coronavirus infection is mediated by the binding of its spike protein to the angiotensin-converting enzyme 2 (ACE2), which plays a pivotal role in the renin-angiotensin system (RAS). The study of RAS dysregulation due to SARS-CoV-2 infection is fundamentally important for a better understanding of the pathogenic mechanisms and risk factors associated with COVID-19 coronavirus disease, and to design effective therapeutic strategies. In this context, we developed a mathematical model of RAS based on data regarding protein and peptide concentrations; the model was tested on clinical data from healthy normotensive and hypertensive individuals. We then used our model to analyze the impact of SARS-CoV-2 infection on RAS, which we modeled through a down-regulation of ACE2 as a function of viral load. We also used it to predict the effect of RAS-targeting drugs, such as RAS-blockers, human recombinant ACE2, and angiotensin 1-7 peptide, on COVID-19 patients; the model predicted an improvement of the clinical outcome for some drugs and a worsening for others.
