Decrypting the role of predicted SARS-CoV-2 miRNAs in COVID-19 pathogenesis: A bioinformatics approach

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a highly transmissible virus causing the ongoing global pandemic, COVID-19. Evidence suggests that viral and host microRNAs play pivotal roles in progression of such infections. The decisive impact of viral miRNAs and their putative targets in modulating the transcriptomic profile of its host, however remains unexplored. We hypothesized that the SARS-CoV-2 derived miRNAs can potentially play a contributory role in its pathogenicity and aid in its survival. A series of computational tools predicted 34 SARS-CoV-2 encoded miRNAs and their putative targets in the host. Immune and apoptotic pathways were identified as most enriched pathways. Further investigation using a dataset of SARS-CoV-2 infected cells (available from public repository- GSE150392) revealed that 46 genes related to immune and apoptosis-related functions were deregulated. Of these 46 genes, 42 genes were identified to be significantly up-regulated and 4 genes were down-regulated . In silico analysis revealed all of the these significantly down-regulated genes to be putative targets of 9 out of 34 of our predicted viral miRNAs. Overall, 123 out of 324 genes that are differentially regulated in SARS-CoV2 infected cells, and also identified as putative targets of viral miRNAs, were found to be significantly down-regulated. KEGG pathway analysis using these genes revealed p53 signaling as the most enriched pathway – a pathway that is known to influence immune responses. This study thus provides the theoretical foundation for the underlying molecular mechanisms involved in progression of viral pathogenesis.

Non-coding RNAs: the silent regulators of health and diseases

“…The key miRNAs identified (miR-4433b-5p, miR-6780b-3p, miR-6883-3p, miR-320b, miR-7111-3p, miR-4755-3p, miR-320c, and miR-6511a-3p) in this study were found to be involved in PI3K/AKT, Wnt/β-catenin, and STAT3 signaling pathways. Interestingly, similar pathways have been reported to be significantly associated signaling pathways in SARS-CoV2 infection in a bioinformatics analysis conducted by our lab on publicly available datasets [ 15 ]. The findings of this new study urge the need for further study on a larger number of participants.…”

p53/NF-kB Balance in SARS-CoV-2 Infection: From OMICs, Genomics and Pharmacogenomics Insights to Tailored Therapeutic Perspectives (COVIDomics)

“…In this scenario, the efforts in optimizing vaccination strategies need to be associated with efforts in establishing “ready-to-use” therapeutic strategies for symptomatic patients for which a definite cure is still missing. In this regard, much effort has been recently made to elucidate the molecular mechanisms and intracellular pathways mostly involved in both SARS-CoV-2 infection and COVID-19 pathophysiological processes; also by using bioinformatics approaches ( Alnajeebi et al, 2022 ; Hasankhani et al, 2021 ; Kwan et al, 2021 ; Rahaman et al, 2021 ). These studies have shown that genes related to immune and apoptosis-related functions were deregulated, and further analysis revealed that p53 signaling was one of the most enriched pathway upon SARS-CoV-2 infection.…”

microRNAs and Inflammatory Immune Response in SARS-CoV-2 Infection: A Narrative Review

“…Rahaman et al [64] applied a series of computational tools to predict 34 SARS-CoV-2encoded miRNAs and their presumptive targets in human host; the immune and apoptotic pathways were selected as the most represented pathways (p53 signaling, cytokine receptor interaction, toll-like receptor (TLR) signaling, NOD-like receptor signaling and Jak-STAT signaling). A further investigation employing a dataset of SARS-CoV-2-infected cells revealed that 46 genes related to immune and apoptosis functions were deregulated during viral infection.…”