High affinity of host human microRNAs to SARS-CoV-2 genome: An in silico analysis

Abstract

Background: Coronavirus disease 2019 (COVID-19) caused by a novel betacoronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has attracted top health concerns worldwide within a few months after its appearance. Since viruses are highly dependent on the host small RNAs (microRNAs) for their replication and propagation, in this study, top miRNAs targeting SARS-CoV-2 genome and top miRNAs targeting differentially expressed genes (DEGs) in lungs of patients infected with SARS-CoV-2, were predicted.

Methods: All human mature miRNA sequences were acquired from miRBase database. MiRanda tool was used to predict the potential human miRNA binding sites on the SARS-CoV-2 genome. EdgeR identified differentially expressed genes (DEGs) in response to SARS-CoV-2 infection from GEO147507 data. Gene Set Enrichment Analysis (GSEA) and DEGs annotation analysis were performed using ToppGene and Metascape tools.

Results: 160 miRNAs with a perfect matching in the seed region were identified. Among them, there was 15 miRNAs with more than three binding sites and 12 miRNAs with a free energy binding of -29 kCal/Mol. MiR-29 family had the most binding sites (11 sites) on the SARS-CoV-2 genome. MiR-21 occupied four binding sites and was among the top miRNAs that targeted up-regulated DEGs. In addition to miR-21, miR-16, let-7b, let-7e, and miR-146a were the top miRNAs targeting DEGs.

Conclusion: Collectively, more experimental studies especially miRNA-based studies are needed to explore detailed molecular mechanisms of SARS-CoV-2 infection. Moreover, the role of DEGs including STAT1, CCND1, CXCL-10, and MAPKAPK2 in SARS-CoV-2 should be investigated to identify the similarities and differences between SARS-CoV-2 and other respiratory viruses.

Keywords: COVID-19; SARS-CoV-2; miR-21; miR-29; microRNA.

Fig. 1

Schematic representation of human miRNA-binding sites on the SARS-CoV-2 genome (29903 bp). Different parts of the genome including untranslated regions (UTRs) (gray), coding sequences (different colors), stem loops (red), and miRNAs that bind to them are shown. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 2

Gene set enrichment analyses. GO and KEGG pathway analysis of all up- (A) and down-regulated (B) genes in response to SARS-COV-2 infection.

Fig. 3

Pie chart of top miRNAs that target DEGs in response to SARS-CoV-2 infection. (A) and (B) refer to all the up- and down- regulated DEGs, (C) and (D) refer to up- down- regulated DEGs involved in viral biological processes, respectively. Enrichment analyses of GO and KEGG pathways for DEGs that are targeted by top miRNAs in response to SARS-CoV-2 infection. (E) and (F) refer to all the up- and down- regulated DEGs, (G) and (H) refer to the up- and down- regulated DEGs involved in viral biological processes, respectively.

Fig. 4

MiRNA-mRNA network analysis in response to SARS-CoV-2 infection. Networks constructed between up- (A) and down- (B) regulated mRNA and top miRNAs, which target them. Yellow diamonds represent miRNAs and small light blue dots represent mRNAs. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 5

MiRNA-mRNA network analysis of DEGs involved in viral biological processes in response to SARS-CoV-2 infection. Networks constructed between up-(A) and down-(B) regulated mRNAs and top miRNAs, which target them. Yellow diamonds represent miRNAs, small light blue dots represent mRNAs, and green rectangles represent viral biological processes. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)