Pyroptosis and Its Role in SARS-CoV-2 Infection

Zsofia Agnes Bittner; Markus Schrader; Shilpa Elizabeth George; Ralf Amann

doi:10.3390/cells11101717

Pyroptosis and Its Role in SARS-CoV-2 Infection

Cells. 2022 May 23;11(10):1717. doi: 10.3390/cells11101717.

Authors

Zsofia Agnes Bittner¹, Markus Schrader², Shilpa Elizabeth George¹, Ralf Amann¹

Affiliations

¹ Department of Immunology, Interfaculty Institute for Cell Biology, University of Tübingen, 72076 Tübingen, Germany.
² Department of Radiooncology, Marienhospital Stuttgart, 70199 Stuttgart, Germany.

Abstract

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.

Keywords: NLRP3; SARS-CoV-2; gasdermins; interleukin-1β; pyroptosis.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

COVID-19*
Caspases / metabolism
Humans
Inflammasomes / metabolism
Intracellular Signaling Peptides and Proteins / metabolism
NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
Phosphate-Binding Proteins / metabolism
Pyroptosis*
SARS-CoV-2

Substances

Inflammasomes
Intracellular Signaling Peptides and Proteins
NLR Family, Pyrin Domain-Containing 3 Protein
Phosphate-Binding Proteins
Caspases

Grants and funding

This research was supported in part by the EXIST Forschungstransfer of the German Ministry for Economic Affairs and Climate Action, which is co-financed by the European Social Fund. We acknowledge support by the Open Access Publishing Fund of the University of Tübingen.