Pyroptosis is an inflammatory mode of cell death that contributes to the cytokine storm associated with severe cases of coronavirus disease 2019 (COVID-19). Central to pyroptosis induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the formation of the NLRP3 inflammasome . Inflammasome formation, and by extension pyroptosis, may be inhibited by certain anti-inflammatory drugs. One such drug, tranilast, is currently being evaluated as a COVID-19 treatment target in a clinical trial. In this study, we present a single-cell mathematical model that captures the formation of the NLRP3 inflammasome, pyroptotic cell death and drug-responses to tranilast . The model is formulated in terms of a system of ordinary differential equations (ODEs) that describe the dynamics of proteins involved in pyroptosis. The model demonstrates that tranilast delays the formation of the NLRP3 inflammasome, and thus may alter the mode of cell death from inflammatory (pyroptosis) to non-inflammatory ( e.g., apoptosis)  .
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 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 being implemented in a SARS-CoV-2 Tissue Simulator, in collaboration with a multidisciplinary coalition investigating within host-dynamics of COVID-19. In this paper, we provide an overview of the SARS-CoV-2 Tissue Simulator and highlight the effects of pyroptosis on a cellular level .
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contributes
can contribute
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Central to pyroptosis
The formation of the NLRP3 inflammasome is central to pyroptosis, which may be
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is the formation of the NLRP3 inflammasome
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One such drug, tranilast, is currently being evaluated as a COVID-19 treatment target in a clinical trial.
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drug-responses to tranilast
responses to anti-inflammatory intervention that hinder the formation of the NLRP3 inflammasome
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proteins
the biological components
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The model demonstrates that tranilast delays
Our results demonstrate that an anti-inflammatory drug can delay
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. The single-cell model is being implemented in a SARS-CoV-2 Tissue Simulator, in collaboration with a multidisciplinary coalition investigating within host-dynamics of COVID-19. In this paper, we provide an overview of the SARS-CoV-2 Tissue Simulator and highlight the effects of pyroptosis on a cellular level