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

Highlights

• Ab-intio based screening revealed novel miRNAs in VOCs (Delta and Omicron) compared to Reference genome.

• In Delta and Omicron, most unique miRNAs were traced at the terminal and origin positions of the genome respectively.

• Delta target genes were involved in Human cytomegalovirus infection, Breast cancer, Apoptosis, and Neurotrophin signaling etc.

• ZEB2 was found to be common target gene among the Reference, Delta and Omicron.

Abstract

COVID-19 related morbidities and mortalities are still continued due to the emergence of new variants of SARS-CoV-2. In the last few years, viral miRNAs have been the centre of study to understand the disease pathophysiology. In this work, we aimed to predict the change in coding potential of the viral miRNAs in SARS-CoV-2′s VOCs, Delta and Omicron compared to the Reference (Wuhan origin) strain using bioinformatics tools. After ab-intio based screening by the Vmir tool and validation, we retrieved 22, 6, and 6 pre-miRNAs for Reference, Delta, and Omicron. Most of the predicted unique pre-miRNAs of Delta and Omicron were found to be encoded from the terminal and origin of the genomic sequence, respectively. Mature miRNAs identified by MatureBayes from the unique pre-miRNAs were used for target identification using miRDB. A total of 1786, 216, and 143 high-confidence target genes were captured for GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis. The GO and KEGG pathways terms analysis revealed the involvement of Delta miRNAs targeted genes in the pathways such as Human cytomegalovirus infection, Breast cancer, Apoptosis, Neurotrophin signaling, and Axon guidance whereas the Sphingolipid signaling pathway was found for the Omicron. Furthermore, we focussed our analysis on target genes that were validated through GEO’s (Gene Expression Omnibus) DEGs (Differentially Expressed Genes) dataset, in which FGL2, TNSF12, OGN, GDF11, and BMP11 target genes were found to be down-regulated by Reference miRNAs and YAE1 and RSU1 by Delta. Few genes were also observed to be validated among in up-regulated gene set of the GEO dataset, in which MMP14, TNFRSF21, SGMS1, and TMEM192 were related to Reference whereas ZEB2 was detected in all three strains. This study thus provides an in-silico based analysis that deciphered the unique pre-miRNAs in Delta and Omicron compared to Reference. However, the findings need future wet lab studies for validation.