A Mini-Review on Cell Cycle Regulation of Coronavirus Infection

Su, Mingjun; Chen, Yaping; Qi, Shanshan; Da, Shi; Feng, Li; Sun, Dongbo

doi:10.3389/fvets.2020.586826

Cited by 52 publications

(54 citation statements)

References 44 publications

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“…TRAF3IP2 encodes for ACT1, an adaptor protein possessing E3-ubiquitin ligase activity involved in IL-17 and NF-κB signaling pathways (Li et al, 2000). The role of NF-κB and IL-17 signaling may be directly proviral by establishing a cellular environment conducive to viral replication, or may negatively affect the host cell by promoting cell death (DeDiego et al, 2014; Kircheis et al, 2020; Park and Hong, 2016; Poppe et al, 2017; Su et al, 2020).…”

Section: Resultsmentioning

confidence: 99%

Genome-wide, bidirectional CRISPR screens identify mucins as critical host factors modulating SARS-CoV-2 infection

Biering

Sarnik

Wang

et al. 2021

Preprint

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SUMMARYSARS-CoV-2 can cause a range of symptoms in infected individuals, from mild respiratory illness to acute respiratory distress syndrome. A systematic understanding of the host factors mediating viral infection or restriction is critical to elucidate SARS-CoV-2 host-pathogen interactions and the progression of COVID-19. To this end, we conducted genome-wide CRISPR knockout and activation screens in human lung epithelial cells with endogenous expression of the SARS-CoV-2 entry factors ACE2 and TMPRSS2. These screens uncovered proviral and antiviral host factors across highly interconnected host pathways, including components implicated in clathrin transport, inflammatory signaling, cell cycle regulation, and transcriptional and epigenetic regulation. We further identified mucins, a family of high-molecular weight glycoproteins, as a prominent viral restriction network. We demonstrate that multiple membrane-anchored mucins are critical inhibitors of SARS-CoV-2 entry and are upregulated in response to viral infection. This functional landscape of SARS-CoV-2 host factors provides a physiologically relevant starting point for new host-directed therapeutics and suggests interactions between SARS-CoV-2 and airway mucins of COVID-19 patients as a host defense mechanism.

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Section: Resultsmentioning

confidence: 99%

Genome-wide, bidirectional CRISPR screens identify mucins as critical host factors modulating SARS-CoV-2 infection

Biering

Sarnik

Wang

et al. 2021

Preprint

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“…Our workflow (modified) has also provided in silico confirmation of the anti-inflammatory and pro-immune effects of oxytocin 70 and the antidepressant fluoxetine 71 , which is also currently in trial for the treatment of COVID-19 (NCT04377308, and others). Interestingly, pathways related to Cell Cycle, and CDK and TP53 transcriptional regulation of cell cycle genes were predominately identified following analysis of the patient sample datasets and likely indicate changes in cell cycle regulation following SARS-CoV-2 infection 72 . In addition to immune dysregulation, biological pathway analysis also supports targeting viral replication processes in SARS-CoV-2 infection.…”

Section: Resultsmentioning

confidence: 99%

Identification of candidate repurposable drugs to combat COVID-19 using a signature-based approach

O’Donovan

Imami

Eby

et al. 2021

Sci Rep

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The COVID-19 pandemic caused by the novel SARS-CoV-2 is more contagious than other coronaviruses and has higher rates of mortality than influenza. Identification of effective therapeutics is a crucial tool to treat those infected with SARS-CoV-2 and limit the spread of this novel disease globally. We deployed a bioinformatics workflow to identify candidate drugs for the treatment of COVID-19. Using an “omics” repository, the Library of Integrated Network-Based Cellular Signatures (LINCS), we simultaneously probed transcriptomic signatures of putative COVID-19 drugs and publicly available SARS-CoV-2 infected cell lines to identify novel therapeutics. We identified a shortlist of 20 candidate drugs: 8 are already under trial for the treatment of COVID-19, the remaining 12 have antiviral properties and 6 have antiviral efficacy against coronaviruses specifically, in vitro. All candidate drugs are either FDA approved or are under investigation. Our candidate drug findings are discordant with (i.e., reverse) SARS-CoV-2 transcriptome signatures generated in vitro, and a subset are also identified in transcriptome signatures generated from COVID-19 patient samples, like the MEK inhibitor selumetinib. Overall, our findings provide additional support for drugs that are already being explored as therapeutic agents for the treatment of COVID-19 and identify promising novel targets that are worthy of further investigation.

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“…The Aurora Kinase B (AURKB) and Aurora Kinase A (AURKA) were found SARS-CoV-2 as DEGs in Caco-2 cells [ 47 ]. The Cyclin-Dependent Kinase 1 (CDK1) genes interact with the thrombocytopenia syndrome virus which initiates the cells into the M phase [ 48 ]. The Cell Division Cycle 20 (CDC20) and CDK1 were also found as potential biomarkers for hepatocellular carcinoma [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics and machine learning approach identifies potential drug targets and pathways in COVID-19

Auwul

Rahman²,

Göv

et al. 2021

Briefings in Bioinformatics

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Current coronavirus disease-2019 (COVID-19) pandemic has caused massive loss of lives. Clinical trials of vaccines and drugs are currently being conducted around the world; however, till now no effective drug is available for COVID-19. Identification of key genes and perturbed pathways in COVID-19 may uncover potential drug targets and biomarkers. We aimed to identify key gene modules and hub targets involved in COVID-19. We have analyzed SARS-CoV-2 infected peripheral blood mononuclear cell (PBMC) transcriptomic data through gene coexpression analysis. We identified 1520 and 1733 differentially expressed genes (DEGs) from the GSE152418 and CRA002390 PBMC datasets, respectively (FDR < 0.05). We found four key gene modules and hub gene signature based on module membership (MMhub) statistics and protein–protein interaction (PPI) networks (PPIhub). Functional annotation by enrichment analysis of the genes of these modules demonstrated immune and inflammatory response biological processes enriched by the DEGs. The pathway analysis revealed the hub genes were enriched with the IL-17 signaling pathway, cytokine–cytokine receptor interaction pathways. Then, we demonstrated the classification performance of hub genes (PLK1, AURKB, AURKA, CDK1, CDC20, KIF11, CCNB1, KIF2C, DTL and CDC6) with accuracy >0.90 suggesting the biomarker potential of the hub genes. The regulatory network analysis showed transcription factors and microRNAs that target these hub genes. Finally, drug–gene interactions analysis suggests amsacrine, BRD-K68548958, naproxol, palbociclib and teniposide as the top-scored repurposed drugs. The identified biomarkers and pathways might be therapeutic targets to the COVID-19.

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A Mini-Review on Cell Cycle Regulation of Coronavirus Infection

Cited by 52 publications

References 44 publications

Genome-wide, bidirectional CRISPR screens identify mucins as critical host factors modulating SARS-CoV-2 infection

Genome-wide, bidirectional CRISPR screens identify mucins as critical host factors modulating SARS-CoV-2 infection

Identification of candidate repurposable drugs to combat COVID-19 using a signature-based approach

Bioinformatics and machine learning approach identifies potential drug targets and pathways in COVID-19

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