SARS-CoV-2 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 used our model to analyze the impact of SARS-CoV-2 infection on RAS, which we modeled through a downregulation 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. Our model and its predictions constitute a valuable framework for in silico testing of hypotheses about the COVID-19 pathogenic mechanisms and the effect of drugs aiming to restore RAS functionality.
【저자키워드】 SARS-CoV-2, acute respiratory distress syndrome, mathematical modeling, renin angiotensin system, RAS-blockers, 【초록키워드】 COVID-19, coronavirus disease, ACE2, coronavirus, Risk factors, SARS-COV-2 infection, peptide, drugs, drug, in silico, risk factor, angiotensin-converting enzyme 2, RAS, Spike protein, Clinical outcome, renin-angiotensin system, Protein, Viral, Viral load, mathematical model, Therapeutic strategies, pathogenic mechanism, predict, COVID-19 patients, binding, Angiotensin-converting enzyme, angiotensin, dysregulation, Renin, Clinical data, worsening, hypertensive, downregulation, hypotheses, recombinant ACE2, pathogenic mechanisms, effective, predicted, healthy, individuals, hypothese, mathematical, normotensive, was tested, with COVID-19, 【제목키워드】 Impact, modeling, System,