Modeling the molecular impact of SARS-CoV-2 infection on the renin-angiotensin system

TL;DR

This paper presents a mathematical model of the renin-angiotensin system to understand how SARS-CoV-2 infection impacts it, predicting effects of drugs and aiding therapeutic strategy development.

Contribution

It introduces a novel mathematical model of RAS incorporating SARS-CoV-2 effects, tested on clinical data, and predicts drug impacts on COVID-19 outcomes.

Findings

Model predicts RAS dysregulation due to SARS-CoV-2

Certain RAS-targeting drugs may improve or worsen outcomes

Model validated with data from healthy and hypertensive individuals

Abstract

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.