A bioinformatic approach of targeting SARS-CoV-2 replication by silencing a conserved alternative reserve of the orf8 gene using host miRNAs

Goud, Vaggu Raghavendra; Chakraborty, Rajasree; Chakraborty, Averi; Lavudi, Kousalya; Patnaik, Sriram; Sharma, Swati; Patnaik, Srinivas

doi:10.1016/j.compbiomed.2022.105436

Cited by 7 publications

(6 citation statements)

References 108 publications

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“…[7][8][9] In particular, it is pointed out that the replicative fitness of the virus is not affected by the truncation or silencing of ORF8 possibly due to the complementing effect of ORF7a. 10 However, there are also significant differences between ORF8 and ORF7a: 1. There is an ORF8-specific region with about 35 residues that is structurally distinct from ORF7a and other Ig-like folds.…”

Section: Introductionmentioning

confidence: 99%

In silicostudy on the effects of disulfide bonds in ORF8 of SARS-CoV-2

Cheng

Peng

2022

Phys. Chem. Chem. Phys.

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Section: Introductionmentioning

confidence: 99%

In silicostudy on the effects of disulfide bonds in ORF8 of SARS-CoV-2

Cheng

Peng

2022

Phys. Chem. Chem. Phys.

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“…There are also reports that ORF8 modulates vesicular traffic through the unfolded protein response and, therefore, ER stress by stimulating the ATF6 and IRE1 pathways through the upregulation of the GRP78 and GRP94 chaperones [27]. Another small corona virus protein ORF9b interacted with Tom70 mitochondrial chaperone as revealed by cryo-electron microscopy [28].…”

Section: Resultsmentioning

confidence: 96%

Untitled

2022

IJCMER

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In HIV mediated pathogenesis, small trans activator proteins (TAT, NEF, REV) modulate transcription of cellular genes. Similarly, preliminary reports indicated that corona virus ORF8 protein acts as histone mimics disrupting chromatic structure with many epigenetic changes and immune modulator functions. ORF8 protein had also some similarities to immunoglobulin domains and inhibited HMC-1 and IFN-beta functions.During evolution a 382-nucleotide deletion (∆382) in the ORF8 region of the corona virus genome leads to weak virus load and weak pathogenicity (accession no.MT374101). We BLAST searched deletion boundary and was selected few ORF8 protein truncated mutants. The C>T base change at 27972nt and another A>T base change at 28095nt created two termination codons (CAA=TAA and AAA=TAA) to produce 26AA and 67AA long ORF8 truncated proteins. Similar Blast-N search with oligonucleotides selected at the mutation boundaries gave many ORF8 mutants with distinct S24L, V32L, P38S, R52I, A65V, Y73C, L84S, K92E and V100L mutations with or without TAA termination mutations.Major mutations found in B.1.1.7 lineage which had spike 69HV and 145Y mutations and ORF1ab polyprotein 3675KSF deletion. However, one ORF8 mutant (accession no. OW221449) belongs to Omicron BA.2 variant with 24LPP spike deletion and others to Omicron BA.5 variants (accession nos. OP733645 and OP671680) with 24LPP and 69HV deletion in the spike protein. One termination codon mutant (accession no. OP711842) has also 63nt ORF7a/b deletions. Mutation did not change the hairpin structure in the ORF8 gene and ORF8 protein formed dimeric stable globular 3-D structure to interact with many host proteins. Clearly, generation of such abundant B.1.1.7 lineage ORF8 protein truncated mutants may be one of the causes for the extinction of Alpha variant of corona virus in 2021. Roles of ORF8 mutants as host proteins modulator were explained in light of other deletions and mutations in corona virus genome.

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“…Biomarkers including NEK7 [686] and CAV1 [689] were associated with the risk of pneumonia. Biomarkers includingNEK7 [718], CAV1 [720], TRIB3 [707], has-mir-8057 [828], hsa-mir-1537-5p [829], STAT1 [830], and TP53 [831] are highly associated with viral respiratory diseases.Biomarkers including NEK7 [449], TRIB3 [452], CAV1 [463],NFYA (nuclear transcription factor Y subunit alpha) [817], STAT1 [832], and TP53 [833] played an important role in the pulmonary hypertension. Biomarkers including CAV1 [148], TRIB3 [120], STAT1 [834], TP53 [835], and NFKB1 [836] have been reported in obesity.…”

Section: Discussionmentioning

confidence: 99%

Study on Potential Differentially Expressed Genes in Idiopathic Pulmonary Fibrosis by Bioinformatics and Next-Generation Sequencing Data Analysis

Giriyappagoudar,

Vastrad,

Horakeri

et al. 2023

Biomedicines

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Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with reduced quality of life and earlier mortality, but its pathogenesis and key genes are still unclear. In this investigation, bioinformatics was used to deeply analyze the pathogenesis of IPF and related key genes, so as to investigate the potential molecular pathogenesis of IPF and provide guidance for clinical treatment. Next-generation sequencing dataset GSE213001 was obtained from Gene Expression Omnibus (GEO), and the differentially expressed genes (DEGs) were identified between IPF and normal control group. The DEGs between IPF and normal control group were screened with the DESeq2 package of R language. The Gene Ontology (GO) and REACTOME pathway enrichment analyses of the DEGs were performed. Using the g:Profiler, the function and pathway enrichment analyses of DEGs were performed. Then, a protein–protein interaction (PPI) network was constructed via the Integrated Interactions Database (IID) database. Cytoscape with Network Analyzer was used to identify the hub genes. miRNet and NetworkAnalyst databaseswereused to construct the targeted microRNAs (miRNAs), transcription factors (TFs), and small drug molecules. Finally, receiver operating characteristic (ROC) curve analysis was used to validate the hub genes. A total of 958 DEGs were screened out in this study, including 479 up regulated genes and 479 down regulated genes. Most of the DEGs were significantly enriched in response to stimulus, GPCR ligand binding, microtubule-based process, and defective GALNT3 causes HFTC. In combination with the results of the PPI network, miRNA-hub gene regulatory network and TF-hub gene regulatory network, hub genes including LRRK2, BMI1, EBP, MNDA, KBTBD7, KRT15, OTX1, TEKT4, SPAG8, and EFHC2 were selected. Cyclothiazide and rotigotinethe are predicted small drug molecules for IPF treatment. Our findings will contribute to identification of potential biomarkers and novel strategies for the treatment of IPF, and provide a novel strategy for clinical therapy.

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A bioinformatic approach of targeting SARS-CoV-2 replication by silencing a conserved alternative reserve of the orf8 gene using host miRNAs

Cited by 7 publications

References 108 publications

In silicostudy on the effects of disulfide bonds in ORF8 of SARS-CoV-2

In silicostudy on the effects of disulfide bonds in ORF8 of SARS-CoV-2

Untitled

Study on Potential Differentially Expressed Genes in Idiopathic Pulmonary Fibrosis by Bioinformatics and Next-Generation Sequencing Data Analysis

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