Identification of COVID-19 Infection-Related Human Genes Based on a Random Walk Model in a Virus–Human Protein Interaction Network

Zhang, Yuhang; Zeng, Tao; Lei, Chen; Ding, Shi‐Jian; Huang, Tao; Cai, Yu-Dong

doi:10.1155/2020/4256301

Cited by 19 publications

(17 citation statements)

References 52 publications

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“…Pathway enrichment analysis revealed biological processes involved in host immune function (e.g., immune effector process, cellular response to cytokine stimulus, cytokine-mediated signaling pathway, response to biotic stimulus, cytokine, other organism, external biotic stimulus,) and the response to viruses (e.g., viral process, defense response to virus and other organism). These biological processes have been suggested to have critical roles in the pathogenesis of coronavirus infections [46][47][48]. Lymph nodes maintain and coordinate new immune responses to control the viruses, although age-related lymph nodes changes reduce the ability of B and T cells to proliferate and differentiate in lymph nodes.…”

Section: Discussionmentioning

confidence: 99%

Methylation of Host Genes Associated with Coronavirus Infection from Birth to 26 Years

Rathod

Rahimabad

et al. 2021

Genes

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DNA methylation (DNAm) patterns over time at 1146 CpGs on coronavirus-related genes were assessed to understand whether the varying differences in susceptibility, symptoms, and the outcomes of the SARS-CoV-2 infection in children and young adults could be explained through epigenetic alterations in a host cell’s transcriptional apparatus to coronaviruses. DNAm data from the Isle of Wight birth cohort (IOWBC) at birth, 10, 18, and 26 years of age were included. Linear mixed models with repeated measurements stratified by sex were used to examine temporal patterns, and cluster analysis was performed to identify CpGs following similar patterns. CpGs on autosomes and sex chromosomes were analyzed separately. The association of identified CpGs and expression of their genes were evaluated. Pathway enrichment analyses of the genes was conducted at FDR = 0.05. DNAm at 635 of the 1146 CpGs on autosomes showed statistically significant time effects (FDR = 0.05). The 635 CpGs were classified into five clusters with each representing a unique temporal pattern of DNAm. Of the 29 CpGs on sex chromosomes, DNAm at seven CpGs in males and eight CpGs in females showed time effects (FDR = 0.05). Sex-specific and non-specific associations of DNAm with gene expression were found at 24 and 93 CpGs, respectively. Genes which mapped the 643 CpGs represent 460 biological processes. We suggest that the observed variability in DNAm with advancing age may partially explain differing susceptibility, disease severity, and mortality of coronavirus infections among different age groups.

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Section: Discussionmentioning

confidence: 99%

Methylation of Host Genes Associated with Coronavirus Infection from Birth to 26 Years

Rathod

Rahimabad

et al. 2021

Genes

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“…With the available scientific approaches and computational facilities to model proteins and investigate proteinligand interactions it becomes more supportive to predict the binding of small molecular drugs to protein targets [28,37,38]. Employing density functional theory [39] the geometry of all the molecules proposed as COVID-19 drug candidates, were optimized to understand structural features and hence their contribution to the inhibition or druggable potential.…”

Section: Introductionmentioning

confidence: 99%

Computationally approached inhibition potential of Tinospora cordifolia towards COVID-19 targets

Jena

Munusami²,

et al. 2021

VirusDis.

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The recent emergence of novel coronavirus (SARS-CoV-2) has been a major threat to human society, as the challenge of finding suitable drug or vaccine is not met till date. With increasing morbidity and mortality, the need for novel drug candidates is under great demand. The investigations are progressing towards COVID-19 therapeutics. Among the various strategies employed, the use of repurposed drugs is competing along with novel drug inventions. Based on the therapeutic significance, the chemical constituents from the extract of Tinospora cordifolia belonging to various classes like alkaloids, lignans, steroids and terpenoids are investigated as potential drug candidates for COVID-19. The inhibition potential of the proposed compounds against viral spike protein and human receptor ACE2 were evaluated by computational molecular modeling (Auto dock), along with their ADME/ T properties. Prior to docking, the initial geometry of the compounds were optimized by Density functional theory (DFT) method employing B3LYP hybrid functional and 6-311 ? ? G (d,p) basis set. The results of molecular docking and ADME/T studies have revealed 6 constituents as potential drug candidates that can inhibit the binding of SARS-CoV-2 spike protein with the human receptor ACE2 protein. The narrowed down list of constituents from Tinospora cordifolia paved way for further tuning their ability to inhibit COVID-19 by modifying the chemical structures and by employing computational geometry optimization and docking methods.

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“… 16 , 17 It has recently been shown that one of the main mechanisms of virus pathogenesis is targeting key human genes and suppressing their expression through viral miRNAs. 18 Therefore, study of viral microRNAs allows us to become more familiar with mechanism of coronavirus pathogenesis. In fact, viral microRNAs play a role in completing virus life cycle.…”

Section: Introductionmentioning

confidence: 99%

Interplay between SARS‐CoV‐2‐derived miRNAs, immune system, vitamin D pathway and respiratory system

Karimi

Azari

Yari

et al. 2021

J Cellular Molecular Medi

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The new coronavirus pandemic started in China in 2019. The intensity of the disease can range from mild to severe, leading to death in many cases. Despite extensive research in this area, the exact molecular nature of virus is not fully recognized; however, according to pieces of evidence, one of the mechanisms of virus pathogenesis is through the function of viral miRNAs. So, we hypothesized that SARS‐CoV‐2 pathogenesis may be due to targeting important genes in the host with its miRNAs, which involved in the respiratory system, immune pathways and vitamin D pathways, thus possibly contributing to disease progression and virus survival. Potential miRNA precursors and mature miRNA were predicted and confirmed based on the virus genome. The next step was to predict and identify their target genes and perform functional enrichment analysis to recognize the biological processes connected with these genes in the three pathways mentioned above through several comprehensive databases. Finally, cis‐acting regulatory elements in 5′ regulatory regions were analysed, and the analysis of available RNAseq data determined the expression level of genes. We revealed that thirty‐nine mature miRNAs could theoretically derive from the SARS‐CoV‐2 genome. Functional enrichment analysis elucidated three highlighted pathways involved in SARS‐CoV‐2 pathogenesis: vitamin D, immune system and respiratory system. Our finding highlighted genes' involvement in three crucial molecular pathways and may help develop new therapeutic targets related to SARS‐CoV‐2.

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Identification of COVID-19 Infection-Related Human Genes Based on a Random Walk Model in a Virus–Human Protein Interaction Network

Cited by 19 publications

References 52 publications

Methylation of Host Genes Associated with Coronavirus Infection from Birth to 26 Years

Methylation of Host Genes Associated with Coronavirus Infection from Birth to 26 Years

Computationally approached inhibition potential of Tinospora cordifolia towards COVID-19 targets

Interplay between SARS‐CoV‐2‐derived miRNAs, immune system, vitamin D pathway and respiratory system

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