Modeling the Molecular Impact of SARS-CoV-2 Infection on the Renin-Angiotensin System

Figures

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  Figure 1. Schematic representation of RAS. In the unperturbed system, soluble proteins that are explicitly considered in the model are in blue grey, the peptides in light blue, and the peptide-bound membrane proteins in medium blue. The activities and enzymes considered only through reaction rates are in green. The feedback loop is indicated in blue. In the perturbed system, the drugs are in orange and SARS-CoV-2 in dark red.

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  Figure 2. Dynamical response of RAS to ACE-I (enalapril) administration. Comparison between the computational prediction (green) and the experimental data (brown) of normalized AngI (a) and AngII (b) as a function of time (in hours) after the single dose administration. Continuous lines are obtained through data interpolation. (c) Measured DBP averaged over more than ten ACE-I types as a function of the normalized dosage ξACE−I (dosage divided by maximal dosage) (brown points) and predicted DBP as a function of ξACE−I values considering γACE−I=0.5ξACE−I (continuous green line) and γACE−I=0.4ξACE−I1/4 (dashed green line). (d) Predicted effect of the combination of ACE-I and ARB on DPB values as a function of the normalized drug dosages ξACE−I and ξARB, considering γACE−I=0.5ξACE−I and γARB=0.5ξARB.

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  Figure 3. Simulated response of RAS to viral infection. (a) The γCoV function used to model the effect of the infection as a function of Ct, the cycle threshold of the virus. (b–d) Predictions obtained from our model for the normalized levels of AngII and Ang1-7 and for the physiological PaO2/FiO2 value, as a function of Ct, for normotensive (blue) and hypertensive (red) individuals.

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  Figure 4. Impact of different RAS-blocking drugs in normotensive (blue) and hypertensive (red) SARS-CoV-2 patients. Predicted PAO2/FIO2 value as a function of the cycle threshold value Ct and (a) γACE−I, (b) γARB, and (c) γDRI functions that model the administration of the corresponding drugs.

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  Figure 5. Impact on the PAO2/FIO2 value of the administration of rhACE2 and Ang1-7 in normotensive (blue) and hypertensive (red) SARS-CoV-2 patients. (a) Predicted PAO2/FIO2 values as a function of Ct and γrhACE2. (b) Predicted PAO2/FIO2 values as a function of Ct and ηAng17.