Publication Type : Journal Article
Thematic Areas : Medical Sciences, Biotech
Publisher : International Journal of Integrative Biology
Source : OMICS A Journal of Integrative Biology, Volume 25, Number 12, 2021
Url : https://www.liebertpub.com/doi/10.1089/omi.2021.0155
Keywords : COVID-19, biochemical systems theory, biomarker, scytokine storm, thrombosis, insulin resistance
Campus : Amritapuri
School : School of Biotechnology
Center : Amrita Mind Brain Center, Biotechnology
Department : biotechnology
Year : 2021
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)-1β, 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.
Cite this Research Publication : Sasidharakurup H, Kumar G, Nair B, Diwakar S., Mathematical modeling of SARS-CoV-2 infection network with cytokine storm, oxidative stress, thrombosis, insulin resistance and nitric oxide pathways, OMICS A Journal of Integrative Biology, Volume 25, Number 12, 2021 https://doi.org/10.1089/omi.2021.0155.