The NLRP3 inflammasome and COVID-19: Activation, pathogenesis and therapeutic strategies

Ni Zhao; Bin Di; Li-Li Xu

doi:10.1016/j.cytogfr.2021.06.002

The NLRP3 inflammasome and COVID-19: Activation, pathogenesis and therapeutic strategies

Cytokine Growth Factor Rev. 2021 Oct:61:2-15. doi: 10.1016/j.cytogfr.2021.06.002. Epub 2021 Jun 18.

Authors

Ni Zhao¹, Bin Di², Li-Li Xu³

Affiliations

¹ Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, 210009, China; Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing, 210009, China.
² Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, 210009, China; Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing, 210009, China. Electronic address: dibin@cpu.edu.cn.
³ Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, 210009, China; Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing, 210009, China. Electronic address: 1620174420@cpu.edu.cn.

Abstract

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exhibits a wide spectrum of clinical presentations, ranging from asymptomatic cases to severe pneumonia or even death. In severe COVID-19 cases, an increased level of proinflammatory cytokines has been observed in the bloodstream, forming the so-called "cytokine storm". Generally, nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome activation intensely induces cytokine production as an inflammatory response to viral infection. Therefore, the NLRP3 inflammasome can be a potential target for the treatment of COVID-19. Hence, this review first introduces the canonical NLRP3 inflammasome activation pathway. Second, we review the cellular/molecular mechanisms of NLRP3 inflammasome activation by SARS-CoV-2 infection (e.g., viroporins, ion flux and the complement cascade). Furthermore, we describe the involvement of the NLRP3 inflammasome in the pathogenesis of COVID-19 (e.g., cytokine storm, respiratory manifestations, cardiovascular comorbidity and neurological symptoms). Finally, we also propose several promising inhibitors targeting the NLRP3 inflammasome, cytokine products and neutrophils to provide novel therapeutic strategies for COVID-19.

Keywords: COVID-19; Inhibitor; NLRP3 inflammasomeome; Pathogenesis; SARS-CoV-2.

Publication types

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

MeSH terms

COVID-19 / metabolism*
COVID-19 Drug Treatment*
Cytokine Release Syndrome / drug therapy
Cytokine Release Syndrome / metabolism
Humans
Inflammasomes / drug effects
Inflammasomes / metabolism*
NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
SARS-CoV-2 / pathogenicity*

Substances

Inflammasomes
NLR Family, Pyrin Domain-Containing 3 Protein
NLRP3 protein, human