In silico analysis of genomic landscape of SARS-CoV-2 and its variant of concerns (Delta and Omicron) reveals changes in the coding potential of miRNAs and their target genes

Saini, Sandeep; Khurana, Savi; Saini, Dikshant; Rajput, Saru; Thakur, Chander Jyoti; Singh, Jeevisha; Jaswal, Akanksha; Kapoor, Yogesh; Kumar, Varinder; Saini, Avneet

doi:10.1016/j.gene.2022.147097

Cited by 3 publications

(2 citation statements)

References 97 publications

(104 reference statements)

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“…In COVID-19 patients, it is also regarded as a risk factor for pulmonary fibrosis [ 70 ]. In the enriched MFs, double-stranded DNA binding, chemokine activity [ 71 ], ubiquitin-like protein ligase binding [ 72 ], and RNA polymerase II core promoter proximal region sequence-specific DNA binding [ 73 ] are related to COVID-19. Sequence-specific double-stranded DNA binding [ 74 ] and transcription regulatory region sequence-specific DNA binding [ 75 ] are associated with the development of melanoma and ovarian cancer, respectively.…”

Section: Discussionmentioning

confidence: 99%

In-silico discovery of common molecular signatures for which SARS-CoV-2 infections and lung diseases stimulate each other, and drug repurposing

Alamin,

Rahaman,

Ferdousi

et al. 2024

PLoS ONE

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COVID-19 caused by SARS-CoV-2 is a global health issue. It is yet a severe risk factor to the patients, who are also suffering from one or more chronic diseases including different lung diseases. In this study, we explored common molecular signatures for which SARS-CoV-2 infections and different lung diseases stimulate each other, and associated candidate drug molecules. We identified both SARS-CoV-2 infections and different lung diseases (Asthma, Tuberculosis, Cystic Fibrosis, Pneumonia, Emphysema, Bronchitis, IPF, ILD, and COPD) causing top-ranked 11 shared genes (STAT1, TLR4, CXCL10, CCL2, JUN, DDX58, IRF7, ICAM1, MX2, IRF9 and ISG15) as the hub of the shared differentially expressed genes (hub-sDEGs). The gene ontology (GO) and pathway enrichment analyses of hub-sDEGs revealed some crucial common pathogenetic processes of SARS-CoV-2 infections and different lung diseases. The regulatory network analysis of hub-sDEGs detected top-ranked 6 TFs proteins and 6 micro RNAs as the key transcriptional and post-transcriptional regulatory factors of hub-sDEGs, respectively. Then we proposed hub-sDEGs guided top-ranked three repurposable drug molecules (Entrectinib, Imatinib, and Nilotinib), for the treatment against COVID-19 with different lung diseases. This recommendation is based on the results obtained from molecular docking analysis using the AutoDock Vina and GLIDE module of Schrödinger. The selected drug molecules were optimized through density functional theory (DFT) and observing their good chemical stability. Finally, we explored the binding stability of the highest-ranked receptor protein RELA with top-ordered three drugs (Entrectinib, Imatinib, and Nilotinib) through 100 ns molecular dynamic (MD) simulations with YASARA and Desmond module of Schrödinger and observed their consistent performance. Therefore, the findings of this study might be useful resources for the diagnosis and therapies of COVID-19 patients who are also suffering from one or more lung diseases.

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Section: Discussionmentioning

confidence: 99%

In-silico discovery of common molecular signatures for which SARS-CoV-2 infections and lung diseases stimulate each other, and drug repurposing

Alamin,

Rahaman,

Ferdousi

et al. 2024

PLoS ONE

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show abstract

“…A viral protein from Epstein-Barr Virus (EBV) has also been shown to distinctly modulate the expression of 3 miRNAs between M81 and B95.8 strains [174]. An in silico study on SARS-CoV-2 found redundancy in predicted pre-miRNAs encoded in the viral genomes of different strains, with six unique pre-miRNAs between the Reference (Wuhan), Delta, and Omicron strains [175]. These subtle variations could be used to explain differences in the pathology of different strains or to identify individual strains for diagnostic purposes.…”

Section: Challenges and Future Considerationsmentioning

confidence: 99%

MicroRNAs: Small but Key Players in Viral Infections and Immune Responses to Viral Pathogens

Bauer,

Majumdar,

Williams

et al. 2023

Biology

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Since the discovery of microRNAs (miRNAs) in C. elegans in 1993, the field of miRNA research has grown steeply. These single-stranded non-coding RNA molecules canonically work at the post-transcriptional phase to regulate protein expression. miRNAs are known to regulate viral infection and the ensuing host immune response. Evolving research suggests miRNAs are assets in the discovery and investigation of therapeutics and diagnostics. In this review, we succinctly summarize the latest findings in (i) mechanisms underpinning miRNA regulation of viral infection, (ii) miRNA regulation of host immune response to viral pathogens, (iii) miRNA-based diagnostics and therapeutics targeting viral pathogens and challenges, and (iv) miRNA patents and the market landscape. Our findings show the differential expression of miRNA may serve as a prognostic biomarker for viral infections in regard to predicting the severity or adverse health effects associated with viral diseases. While there is huge market potential for miRNA technology, the novel approach of using miRNA mimics to enhance antiviral activity or antagonists to inhibit pro-viral miRNAs has been an ongoing research endeavor. Significant hurdles remain in terms of miRNA delivery, stability, efficacy, safety/tolerability, and specificity. Addressing these challenges may pave a path for harnessing the full potential of miRNAs in modern medicine.

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Human cytomegalovirus microRNAs: strategies for immune evasion and viral latency

Sabbaghian,

Gheitasi,

Fadaee

et al. 2024

Arch Virol

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In silico analysis of genomic landscape of SARS-CoV-2 and its variant of concerns (Delta and Omicron) reveals changes in the coding potential of miRNAs and their target genes

Cited by 3 publications

References 97 publications

In-silico discovery of common molecular signatures for which SARS-CoV-2 infections and lung diseases stimulate each other, and drug repurposing

In-silico discovery of common molecular signatures for which SARS-CoV-2 infections and lung diseases stimulate each other, and drug repurposing

MicroRNAs: Small but Key Players in Viral Infections and Immune Responses to Viral Pathogens

Human cytomegalovirus microRNAs: strategies for immune evasion and viral latency

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