Modeling the Molecular Impact of SARS-CoV-2 Infection on the Renin-Angiotensin System
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 th...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-11-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/12/12/1367 |
| _version_ | 1827701128401256448 |
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| author | Fabrizio Pucci Philippe Bogaerts Marianne Rooman |
| author_facet | Fabrizio Pucci Philippe Bogaerts Marianne Rooman |
| author_sort | Fabrizio Pucci |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T14:26:25Z |
| format | Article |
| id | doaj.art-a04ae6538a054b9f96e6843cc4a99f04 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T14:26:25Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-a04ae6538a054b9f96e6843cc4a99f042023-11-20T22:55:56ZengMDPI AGViruses1999-49152020-11-011212136710.3390/v12121367Modeling the Molecular Impact of SARS-CoV-2 Infection on the Renin-Angiotensin SystemFabrizio Pucci0Philippe Bogaerts1Marianne Rooman2Computational Biology and Bioinformatics, Université Libre de Bruxelles, CP 165/61, Roosevelt Ave. 50, 1050 Brussels, BelgiumBiosystems Modeling and Control, Université Libre de Bruxelles, CP 165/61, Roosevelt Ave. 50, 1050 Brussels, BelgiumComputational Biology and Bioinformatics, Université Libre de Bruxelles, CP 165/61, Roosevelt Ave. 50, 1050 Brussels, BelgiumSARS-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.https://www.mdpi.com/1999-4915/12/12/1367SARS-CoV-2renin angiotensin systemmathematical modelingRAS-blockersacute respiratory distress syndrome |
| spellingShingle | Fabrizio Pucci Philippe Bogaerts Marianne Rooman Modeling the Molecular Impact of SARS-CoV-2 Infection on the Renin-Angiotensin System Viruses SARS-CoV-2 renin angiotensin system mathematical modeling RAS-blockers acute respiratory distress syndrome |
| title | Modeling the Molecular Impact of SARS-CoV-2 Infection on the Renin-Angiotensin System |
| title_full | Modeling the Molecular Impact of SARS-CoV-2 Infection on the Renin-Angiotensin System |
| title_fullStr | Modeling the Molecular Impact of SARS-CoV-2 Infection on the Renin-Angiotensin System |
| title_full_unstemmed | Modeling the Molecular Impact of SARS-CoV-2 Infection on the Renin-Angiotensin System |
| title_short | Modeling the Molecular Impact of SARS-CoV-2 Infection on the Renin-Angiotensin System |
| title_sort | modeling the molecular impact of sars cov 2 infection on the renin angiotensin system |
| topic | SARS-CoV-2 renin angiotensin system mathematical modeling RAS-blockers acute respiratory distress syndrome |
| url | https://www.mdpi.com/1999-4915/12/12/1367 |
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