SARS-CoV-2 Nsp5 Activates NF-κB Pathway by Upregulating SUMOylation of MAVS

Li, Weiling; Qiao, Jialu; Qin, You; Zong, Shan; Peng, Qian; Liu, Yuchen; Hu, Song; Liu, Wei; Li, Shufen; Shu, Xiji; Sun, Binlian

doi:10.3389/fimmu.2021.750969

Cited by 47 publications

(42 citation statements)

References 53 publications

(57 reference statements)

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“…In case of activated TopNets (Figure 2C), as expected, Calu3 and Vero cells show similar upregulated pathways such as I-kappaB kinase/NF-kappaB signaling, regulation of transcription factor (TF) activity, cytokine mediated signaling pathway, and response to stimulus. These processes are well supported by previous studies (18)(19)(20). Regulation of immune signaling pathways is another process prominently observed in COVID-19, especially production of various cytokines and chemokines (21,22).…”

Section: Overview Of the Approachsupporting

confidence: 84%

A Path-Based Analysis of Infected Cell Line and COVID-19 Patient Transcriptome Reveals Novel Potential Targets and Drugs Against SARS-CoV-2

et al. 2022

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Most transcriptomic studies of SARS-CoV-2 infection have focused on differentially expressed genes, which do not necessarily reveal the genes mediating the transcriptomic changes. In contrast, exploiting curated biological network, our PathExt tool identifies central genes from the differentially active paths mediating global transcriptomic response. Here we apply PathExt to multiple cell line infection models of SARS-CoV-2 and other viruses, as well as to COVID-19 patient-derived PBMCs. The central genes mediating SARS-CoV-2 response in cell lines were uniquely enriched for ATP metabolic process, G1/S transition, leukocyte activation and migration. In contrast, PBMC response reveals dysregulated cell-cycle processes. In PBMC, the most frequently central genes are associated with COVID-19 severity. Importantly, relative to differential genes, PathExt-identified genes show greater concordance with several benchmark anti-COVID-19 target gene sets. We propose six novel anti-SARS-CoV-2 targets ADCY2, ADSL, OCRL, TIAM1, PBK, and BUB1, and potential drugs targeting these genes, such as Bemcentinib, Phthalocyanine, and Conivaptan.

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Section: Overview Of the Approachsupporting

confidence: 84%

A Path-Based Analysis of Infected Cell Line and COVID-19 Patient Transcriptome Reveals Novel Potential Targets and Drugs Against SARS-CoV-2

et al. 2022

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“…Studies have shown that the ACE2-Ang II axis can induce the infiltration of macrophages and secretion of certain cytokines, including IL-6, CCL2, vascular cell adhesion molecule 1 (VCAM-1), and E-selectin, to induce endothelial dysfunction, thrombin formation, and impaired fibrinolysis ( 20 , 22 – 24 ). In addition to the ACE2-Ang II axis, viral protein Nsp5 and spike (S) in SARS-CoV-2 can potently induce inflammatory cytokines and chemokines IL-1β, IL-6, TNF-α, IL-2, CXCL1, CXCL2, and CCL2 expressions in monocytes/macrophage through NF-κB signaling pathways ( 25 , 26 ).…”

Section: Cytokine Secretion Induced By Sars-cov-2 Infectionmentioning

confidence: 99%

The Role of Cytokines and Chemokines in Severe Acute Respiratory Syndrome Coronavirus 2 Infections

Hsu

Peng

et al. 2022

Front. Immunol.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in countless infections and caused millions of deaths since its emergence in 2019. Coronavirus disease 2019 (COVID-19)-associated mortality is caused by uncontrolled inflammation, aberrant immune response, cytokine storm, and an imbalanced hyperactive immune system. The cytokine storm further results in multiple organ failure and lung immunopathology. Therefore, any potential treatments should focus on the direct elimination of viral particles, prevention strategies, and mitigation of the imbalanced (hyperactive) immune system. This review focuses on cytokine secretions of innate and adaptive immune responses against COVID-19, including interleukins, interferons, tumor necrosis factor-alpha, and other chemokines. In addition to the review focus, we discuss potential immunotherapeutic approaches based on relevant pathophysiological features, the systemic immune response against SARS-CoV-2, and data from recent clinical trials and experiments on the COVID-19-associated cytokine storm. Prompt use of these cytokines as diagnostic markers and aggressive prevention and management of the cytokine storm can help determine COVID-19-associated morbidity and mortality. The prophylaxis and rapid management of the cytokine storm appear to significantly improve disease outcomes. For these reasons, this study aims to provide advanced information to facilitate innovative strategies to survive in the COVID-19 pandemic.

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“…SARS-CoV-2 NSP5 can induce the expression of cytokines IL-1β, IL-6, TNF-α, and IL-2 in Calu-3 and THP1 cells. Furthermore, they showed that NSP5 could activate the NF-κB signaling pathway and enhances cytokine expression [48].…”

Section: Resultsmentioning

confidence: 99%

Analysis of Whole-Genome Sequencing of SARS-CoV-2 Reveals Recurrent Mutations among Iranian Patients

Abbasian

Mahdavi

Mahmanzar

et al. 2022

Preprint

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BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new emerging coronavirus that causes coronavirus disease 2019 (COVID-19). Whole-genome tracking of the SARS-CoV-2 enhanced our understanding of the mechanism of disease, control, and prevent COVID-19 infections.Materials and MethodsIn the current study, we investigated 1221 SARS-CoV-2 protein sequences of Iranian SARS-CoV-2 in the public database of the GISAID from January 2019 to April 2022. Prepare a list of suitable samples and preprocess performed by python programming language. To compare and identify mutation patterns SARS-CoV-2 genome was aligned to the Wuhan-Hu-1 as a reference sequence.ResultsOur investigation revealed that spike-P323L, ORF9c-G50N, NSP14-I42V, spike-D614G, NSP4-T492I, nucleocapsid-R203K, nucleocapsid-G204R, membrane-A63T, membrane-Q19E, NSP5-P132H, envelope-T9I, NSP3-G489S, ORF3a-T24I, membrane-D3G, spike-S477N, Spike-D478K, nucleocapsid-S235F, spike-N501Y, nucleocapsid-D3L, and spike-P861H as the most frequent mutations among the Iranian SARS-COV-2 sequences. Furthermore, it was observed that more than 95 % of the SARS-CoV-2 genome, including NSP7, NSP8, NSP9, NSP10, NSP11, and ORF8, had no mutation when compared to the Wuhan-Hu-1. Finally, our data indicated the ORF3a-T24I, NSP3-G489S, NSP5-P132H, NSP14-I42V, envelope-T9I, nucleocapsid-D3L, membrane-Q19E, and membrane-A63T mutations might be one of the responsible factors for the surge in the SARS-CoV-2 omicron variant wave in Iran.DiscussionOur results highlight the value of real-time genomic surveillance that help to identify novel SARS-CoV-2 variants and could be applied to update SARS-CoV-2 diagnostic tools, vaccine design, and understanding of the mechanisms of adaptation to a new host environment.

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SARS-CoV-2 Nsp5 Activates NF-κB Pathway by Upregulating SUMOylation of MAVS

Cited by 47 publications

References 53 publications

A Path-Based Analysis of Infected Cell Line and COVID-19 Patient Transcriptome Reveals Novel Potential Targets and Drugs Against SARS-CoV-2

A Path-Based Analysis of Infected Cell Line and COVID-19 Patient Transcriptome Reveals Novel Potential Targets and Drugs Against SARS-CoV-2

The Role of Cytokines and Chemokines in Severe Acute Respiratory Syndrome Coronavirus 2 Infections

Analysis of Whole-Genome Sequencing of SARS-CoV-2 Reveals Recurrent Mutations among Iranian Patients

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