miRNAs in SARS-CoV 2: A Spoke in the Wheel of Pathogenesis

The rapid emergence of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-- CoV-2) has resulted in an increased mortality rate across the globe. However, the underlying mechanism of SARS-CoV-2 altering human immune response is still elusive. The existing literature on miRNA mediated pathogenesis of RNA virus viz. Dengue virus, West Nile virus, etc. raises a suspicion that miRNA encoded by SARS-CoV-2 might facilitate virus replication and regulate the host's gene expression at the post-transcriptional level.

We investigated this possibility via computational prediction of putative miRNAs encoded by the SARS-CoV-2 genome using a novel systematic pipeline that predicts putative mature-miRNA and their targeted genes transcripts. To trace down if viral-miRNAs targeted the genes critical to the immune pathway, we assessed whether mature miRNA transcripts exhibit effective hybridization with the 3'UTR region of human gene transcripts. Conversely, we also tried to study human miRNA-mediated viral gene regulation to get insight into the miRNA mediated offense and defense mechanism of virus and its host organisms in toto.

Our analysis led us to shortlist six putative miRNAs that target, majorly, genes related to cell proliferation/ differentiation/signaling, and senescence. Nonetheless, they also target immune-related genes that directly/ indirectly orchestrate immune pathways like TNF (Tumor Necrosis Factor) signaling and Chemokine signaling pathways putatively serving as the nucleus to cytokine storms.

Besides, these six miRNAs were found to be conserved so far across 80 complete genomes of SARS-CoV-2 (NCBI Virus, last assessed 12 April 2020) including Indian strains that are also targeted by 7 human miRNAs and can, therefore, be exploited to develop MicroRNA-Attenuated Vaccines.