SARS-CoV-2 putative mi-RNAs may target host immune system and cellular mechanisms to mediate pathogenesis-an in silico and in vivo study

Introduction: The exact role of epigenetics in the pathogenesis of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is unclear. Herein we have hypothesized that viral micro RNAs (miRNAs) may modulate host cellular and immune responses which may lead to varied clinical presentations. Methods: Using bioinformatics tools, we have first predicted putative miRNAs in the genotype of the SARS-CoV-2 and their potential gene targets. Thereafter, quantification of mRNA of key genes regulating inflammation, coagulation, neuropsychiatric functions, fibrosis, and glucose metabolism was evaluated in the peripheral blood mononuclear cells and bone marrow of patients suffering from different severities of SARS-CoV-2 infection. Results: Key genes regulating innate immunity, lymphopoiesis, T-cell and B-cell development, cytokine storm, coagulation pathways, fibrosis, neuropsychiatric manifestations, glucose metabolism, and olfaction were significantly downregulated in severe infection when compared with mild infection. Downregulated genes mRNA recovered to normal/near normal levels on recovery from infection. Conclusion: SARS-CoV-2 miRNAs appear promising players in the pathogenesis of COVID-19. Strategies silencing these miRNAs may be explored as potential therapeutic targets.