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

Abstract

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 R0. It turns out that threshold dynamics is determined by the sign of R0−1. Under some suitable parameters, our numerical simulations show that environmental heterogeneity may increase transmission risk R0 in time periodic environments. We may underestimate R0 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.