tetano
Editor, Senior Moderator
Viruses
. 2020 Nov 30;12(12):E1367.
doi: 10.3390/v12121367.
Modeling the Molecular Impact of SARS-CoV-2 Infection on the Renin-Angiotensin System
Fabrizio Pucci[SUP] 1 [/SUP], Philippe Bogaerts[SUP] 2 [/SUP], Marianne Rooman[SUP] 1 [/SUP]
Affiliations
Abstract
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.
Keywords: RAS-blockers; SARS-CoV-2; acute respiratory distress syndrome; mathematical modeling; renin angiotensin system.
. 2020 Nov 30;12(12):E1367.
doi: 10.3390/v12121367.
Modeling the Molecular Impact of SARS-CoV-2 Infection on the Renin-Angiotensin System
Fabrizio Pucci[SUP] 1 [/SUP], Philippe Bogaerts[SUP] 2 [/SUP], Marianne Rooman[SUP] 1 [/SUP]
Affiliations
- PMID: 33265982
- DOI: 10.3390/v12121367
Abstract
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.
Keywords: RAS-blockers; SARS-CoV-2; acute respiratory distress syndrome; mathematical modeling; renin angiotensin system.