New insights into pharmacologic inhibition of pyroptotic cell death by necrosulfonamide: A PDE model

Pyroptosis is a highly inflammatory form of cell death, which uses intracellularly generated pores to destroy electrolyte homeostasis and perform cell death. Gasdermin D, the pore-forming effector protein of pyroptosis, plays a critical role in coordinating membrane lysis and the release of highly inflammatory molecules. Recently, necrosulfonamide as a direct chemical inhibitor of gasdermin D has been confirmed to bind gasdermin D to inhibit pyroptotic cell death. To provide a more effective theoretical guidance for the influence of gasdermin D inhibitors on pyroptosis, we derive a novel PDE model from the genetic level, and study its threshold dynamics in terms of the basic reproduction number $R_0$. It turns out that threshold dynamics is determined by the sign of $R_0-1$. Under some suitable parameters, our numerical simulations show that environmental heterogeneity may increase transmission risk $R_0$ in time periodic environments. We may underestimate $R_0$ if the time average system is used. Based on some published experimental data, the administration of necrosulfonamide maybe strengthen the health condition of patients rapidly, which may become a new strategy to maintain CD4+ T cell counts at a safe level.