SARS‐CoV‐2 nucleocapsid suppresses host pyroptosis by blocking Gasdermin D cleavage

Ma, Juan; Zhu, Fangrui; Zhao, Min; Shao, Fei; Yu, Dou; Ma, Jiangwen; Zhang, Xusheng; Li, Weitao; Qian, Ying; Zhang, Yan; Jiang, Dong; Wang, Shuo; Xia, Pengyan

doi:10.15252/embj.2021108249

Cited by 85 publications

(86 citation statements)

References 52 publications

(79 reference statements)

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“…Coincidentally, during our revision process, the latest study demonstrated that SARS-CoV-2 nucleocapsid protein associates with hGSDMD in cells and inhibits hGSDMD cleavage in vitro and in vivo . SARS-CoV-2 nucleocapsid directly binds the linker region of GSDMD to protect GSDMD tetrapeptide from being cut by caspase-1 ( 57 ). This indicates that other proteins of coronaviruses also participate in suppressing GSDMD-mediated pyroptosis.…”

Section: Discussionmentioning

confidence: 99%

Coronaviruses Nsp5 Antagonizes Porcine Gasdermin D-Mediated Pyroptosis by Cleaving Pore-Forming p30 Fragment

Shi

Wang

et al. 2022

mBio

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Section: Discussionmentioning

confidence: 99%

Coronaviruses Nsp5 Antagonizes Porcine Gasdermin D-Mediated Pyroptosis by Cleaving Pore-Forming p30 Fragment

Shi

Wang

et al. 2022

mBio

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“…High throughput metagenomic sequencing and pathway analysis of cells obtained from the upper airway of patients with early Covid-19 infection showed a major suppression of inflammatory responses notably of genes mediating inflammasome priming and monocyte/macrophage recruitment. Interestingly, recent work has suggested inflammasome suppression by the Sars-Cov-2 nucleocapsid protein because of impaired GSDMD cleavage 40 . Together these studies strongly suggest an immunosuppressive effect of early Covid-19 infection, mediated in part by the viral E protein, that is permissive to continued viral replication leading to high viral titers increasing infectiousness and potential downstream adverse effects to the host.…”

Section: Discussionmentioning

confidence: 99%

Modulation of the NLRP3 inflammasome by Sars-CoV-2 Envelope protein

Yalçinkaya

Liu

Islam

et al. 2021

Sci Rep

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Despite the initial success of some drugs and vaccines targeting COVID-19, understanding the mechanism underlying SARS-CoV-2 disease pathogenesis remains crucial for the development of further approaches to treatment. Some patients with severe Covid-19 experience a cytokine storm and display evidence of inflammasome activation leading to increased levels of IL-1β and IL-18; however, other reports have suggested reduced inflammatory responses to Sars-Cov-2. In this study we have examined the effects of the Sars-Cov-2 envelope (E) protein, a virulence factor in coronaviruses, on inflammasome activation and pulmonary inflammation. In cultured macrophages the E protein suppressed inflammasome priming and NLRP3 inflammasome activation. Similarly, in mice transfected with E protein and treated with poly(I:C) to simulate the effects of viral RNA, the E protein, in an NLRP3-dependent fashion, reduced expression of pro-IL-1β, levels of IL-1β and IL-18 in broncho-alveolar lavage fluid, and macrophage infiltration in the lung. To simulate the effects of more advanced infection, macrophages were treated with both LPS and poly(I:C). In this setting the E protein increased NLRP3 inflammasome activation in both murine and human macrophages. Thus, the Sars-Cov-2 E protein may initially suppress the host NLRP3 inflammasome response to viral RNA while potentially increasing NLRP3 inflammasome responses in the later stages of infection. Targeting the Sars-Cov-2 E protein especially in the early stages of infection may represent a novel approach to Covid-19 therapy.

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“…Because NLRP3 inflammasome formation is unaffected by SARS-CoV-2 nucleocapsid protein, the natural consequence of GSDMD protection is the intracellular accumulation of IL-1β and IL-18 that cannot be released. This mechanism could therefore delay the initial antiviral response and contribute to the asymptomatic phase of COVID-19 infection (298). Opposing this evidence, multiple studies have in contrast shown that the inflammasome is activated in COVID-19 patients, linking this activation to a more severe disease (299)(300)(301).…”

Section: Sars-cov-2 Suppression Of the Inflammasome And Pyroptosismentioning

confidence: 99%

SARS-CoV-2 and the Host Cell: A Tale of Interactions

Pizzato¹,

Baraldi²,

Sopetto³

et al. 2022

Front.Virol.

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The ability of a virus to spread between individuals, its replication capacity and the clinical course of the infection are macroscopic consequences of a multifaceted molecular interaction of viral components with the host cell. The heavy impact of COVID-19 on the world population, economics and sanitary systems calls for therapeutic and prophylactic solutions that require a deep characterization of the interactions occurring between virus and host cells. Unveiling how SARS-CoV-2 engages with host factors throughout its life cycle is therefore fundamental to understand the pathogenic mechanisms underlying the viral infection and to design antiviral therapies and prophylactic strategies. Two years into the SARS-CoV-2 pandemic, this review provides an overview of the interplay between SARS-CoV-2 and the host cell, with focus on the machinery and compartments pivotal for virus replication and the antiviral cellular response. Starting with the interaction with the cell surface, following the virus replicative cycle through the characterization of the entry pathways, the survival and replication in the cytoplasm, to the mechanisms of egress from the infected cell, this review unravels the complex network of interactions between SARS-CoV-2 and the host cell, highlighting the knowledge that has the potential to set the basis for the development of innovative antiviral strategies.

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SARS‐CoV‐2 nucleocapsid suppresses host pyroptosis by blocking Gasdermin D cleavage

Cited by 85 publications

References 52 publications

Coronaviruses Nsp5 Antagonizes Porcine Gasdermin D-Mediated Pyroptosis by Cleaving Pore-Forming p30 Fragment

Coronaviruses Nsp5 Antagonizes Porcine Gasdermin D-Mediated Pyroptosis by Cleaving Pore-Forming p30 Fragment

Modulation of the NLRP3 inflammasome by Sars-CoV-2 Envelope protein

SARS-CoV-2 and the Host Cell: A Tale of Interactions

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