Modeling the Molecular Impact of SARS-CoV-2 Infection on the Renin-Angiotensin System.
Viruses
; 12(12)2020 11 30.
Artículo
en Inglés
| MEDLINE | ID: covidwho-948866
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.
Palabras clave
Texto completo:
Disponible
Colección:
Bases de datos internacionales
Base de datos:
MEDLINE
Asunto principal:
Sistema Renina-Angiotensina
/
COVID-19
/
Modelos Teóricos
Tipo de estudio:
Estudio experimental
/
Estudio pronóstico
Límite:
Humanos
Idioma:
Inglés
Año:
2020
Tipo del documento:
Artículo
País de afiliación:
V12121367
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