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Mathematical Modeling of Severe Acute Respiratory Syndrome Coronavirus 2 Infection Network with Cytokine Storm, Oxidative Stress, Thrombosis, Insulin Resistance, and Nitric Oxide Pathways.
Sasidharakurup, Hemalatha; Kumar, Geetha; Nair, Bipin; Diwakar, Shyam.
  • Sasidharakurup H; Amrita Mind Brain Center and Amrita Vishwa Vidyapeetham, Kollam, India.
  • Kumar G; School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam, India.
  • Nair B; School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam, India.
  • Diwakar S; Tata Institute for Genetics and Society, Kodigehalli, Bengaluru, India.
OMICS ; 25(12): 770-781, 2021 12.
Article in English | MEDLINE | ID: covidwho-1528153
ABSTRACT
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a systemic disease affecting not only the lungs but also multiple organ systems. Clinical studies implicate that SARS-CoV-2 infection causes imbalance of cellular homeostasis and immune response that trigger cytokine storm, oxidative stress, thrombosis, and insulin resistance. Mathematical modeling can offer in-depth understanding of the SARS-CoV-2 infection and illuminate how subcellular mechanisms and feedback loops underpin disease progression and multiorgan failure. We report here a mathematical model of SARS-CoV-2 infection pathway network with cytokine storm, oxidative stress, thrombosis, insulin resistance, and nitric oxide (NO) pathways. The biochemical systems theory model shows autocrine loops with positive feedback enabling excessive immune response, cytokines, transcription factors, and interferons, which can imbalance homeostasis of the system. The simulations suggest that changes in immune response led to uncontrolled release of cytokines and chemokines, including interleukin (IL)-1ß, IL-6, and tumor necrosis factor α (TNFα), and affect insulin, coagulation, and NO signaling pathways. Increased production of NETs (neutrophil extracellular traps), thrombin, PAI-1 (plasminogen activator inhibitor-1), and other procoagulant factors led to thrombosis. By analyzing complex biochemical reactions, this model forecasts the key intermediates, potential biomarkers, and risk factors at different stages of COVID-19. These insights can be useful for drug discovery and development, as well as precision treatment of multiorgan implications of COVID-19 as seen in systems medicine.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Thrombosis / Insulin Resistance / Oxidative Stress / Cytokine Release Syndrome / SARS-CoV-2 / COVID-19 / Nitric Oxide Type of study: Prognostic study Limits: Humans Language: English Journal: OMICS Journal subject: Molecular Biology Year: 2021 Document Type: Article Affiliation country: Omi.2021.0155

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Thrombosis / Insulin Resistance / Oxidative Stress / Cytokine Release Syndrome / SARS-CoV-2 / COVID-19 / Nitric Oxide Type of study: Prognostic study Limits: Humans Language: English Journal: OMICS Journal subject: Molecular Biology Year: 2021 Document Type: Article Affiliation country: Omi.2021.0155