Pyroptosis and Its Role in SARS-CoV-2 Infection

The pore-forming inflammatory cell death pathway, pyroptosis, was first described in the early 1990s and its role in health and disease has been intensively studied since. The effector molecule GSDMD is cleaved by activated caspases, mainly Caspase 1 or 11 (Caspase 4/5 in humans), downstream of inflammasome formation. In this review, we describe the molecular events related to GSDMD-mediated pore formation. Furthermore, we summarize the so far elucidated ways of SARS-CoV-2 induced NLRP3 inflammasome formation leading to pyroptosis, which strongly contributes to COVID-19 pathology. We also explore the potential of NLRP3 and GSDMD inhibitors as therapeutics to counter excessive inflammation.

Automated summary

This article mainly introduces the discovery of the pore-forming inflammatory cell death pathway, pyroptosis, and its role in health and disease. The molecular events related to GSDMD-mediated pore formation are emphasized, and the ways of SARS-CoV-2 induced NLRP3 inflammasome formation leading to pyroptosis, which is strongly associated with COVID-19 pathology, are summarized. The potential of NLRP3 and GSDMD inhibitors as therapeutics to counter excessive inflammation is also explored.