A single-cell mathematical model of SARS-CoV-2 induced pyroptosis and the effects of anti-inflammatory intervention
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Pyroptosis is an inflammatory mode of cell death that can contribute to the cytokine storm associated with severe cases of coronavirus disease 2019 (COVID-19). The formation of the NLRP3 inflammasome is central to pyroptosis, which may be induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Inflammasome formation, and by extension pyroptosis, may be inhibited by certain anti-inflammatory drugs. In this study, we present a single-cell mathematical model that captures the formation of the NLRP3 inflammasome, pyroptotic cell death and responses to anti-inflammatory intervention that hinder the formation of the NLRP3 inflammasome. The model is formulated in terms of a system of ordinary differential equations (ODEs) that describe the dynamics of the key biological components involved in pyroptosis. Our results demonstrate that an anti-inflammatory drug can delay the formation of the NLRP3 inflammasome, and thus may alter the mode of cell death from inflammatory (pyroptosis) to non-inflammatory (e.g., apoptosis). The single-cell model is implemented within a SARS-CoV-2 tissue simulator, in collaboration with a multidisciplinary coalition investigating within host-dynamics of COVID-19. In this paper, we additionally provide an overview of the SARS-CoV-2 tissue simulator and highlight the effects of pyroptosis on a cellular level.
Hamis , S J & Macfarlane , F R 2021 , ' A single-cell mathematical model of SARS-CoV-2 induced pyroptosis and the effects of anti-inflammatory intervention ' , AIMS Mathematics , vol. 6 , no. 6 , pp. 6050-6086 . https://doi.org/10.3934/math.2021356
Copyright © 2021 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0).
DescriptionSJH is supported by the Medical Research Council grant MR/R017506/1. The authors would like to thank the SARS-CoV-2 Tissue Simulation Coalition for ongoing collaboration and feedback on model development. Further, this work is part of the RAMP (Rapid Assistance in Modelling the Pandemic) initiative, coordinated by the Royal Society, UK. The authors would like to thank Prof. Mark A.J. Chaplain (University of St Andrews) for coordinating our RAMP Task Team modelling within-host dynamics. SARS-CoV-2 Tissue Simulation Coalition: http://physicell.org/covid19/. RAMP: https://royalsociety.org/topics-policy/health-and-wellbeing/ramp/.
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