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Rev Med Virol ; 30(5): e2140, 2020 09.
Article in English | MEDLINE | ID: covidwho-848179

ABSTRACT

A knowledge-based cybernetic framework model representing the dynamics of SARS-CoV-2 inside the human body has been studied analytically and in silico to explore the pathophysiologic regulations. The following modeling methodology was developed as a platform to introduce a predictive tool supporting a therapeutic approach to Covid-19 disease. A time-dependent nonlinear system of ordinary differential equations model was constructed involving type-I cells, type-II cells, SARS-CoV-2 virus, inflammatory mediators, interleukins along with host pulmonary gas exchange rate, thermostat control, and mean pressure difference. This formalism introduced about 17 unknown parameters. Estimating these unknown parameters requires a mathematical association with the in vivo sparse data and the dynamic sensitivities of the model. The cybernetic model can simulate a dynamic response to the reduced pulmonary alveolar gas exchange rate, thermostat control, and mean pressure difference under a very critical condition based on equilibrium (steady state) values of the inflammatory mediators and system parameters. In silico analysis of the current cybernetical approach with system dynamical modeling can provide an intellectual framework to help experimentalists identify more active therapeutic approaches.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/immunology , Host-Pathogen Interactions/immunology , Lung/immunology , Nonlinear Dynamics , Pneumonia, Viral/immunology , Acute-Phase Proteins/antagonists & inhibitors , Acute-Phase Proteins/genetics , Acute-Phase Proteins/immunology , Angiotensin-Converting Enzyme 2 , Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/therapeutic use , Betacoronavirus/drug effects , Betacoronavirus/growth & development , Body Temperature , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/pathology , Coronavirus Infections/virology , Cytokines/antagonists & inhibitors , Cytokines/genetics , Cytokines/immunology , Epithelial Cells/drug effects , Epithelial Cells/immunology , Epithelial Cells/virology , Gene Expression Regulation , Host-Pathogen Interactions/drug effects , Host-Pathogen Interactions/genetics , Humans , Lung/drug effects , Lung/virology , Macrophages, Alveolar/drug effects , Macrophages, Alveolar/immunology , Macrophages, Alveolar/virology , Pandemics , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/immunology , Pneumonia, Viral/drug therapy , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Pulmonary Gas Exchange/drug effects , Pulmonary Gas Exchange/immunology , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology
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