Bioinformatics evaluation of signaling pathways targeting hsa-miR-1283related to TYK2 and its associated rs2304256 function in patients with COVID-19

viral diseases cause remarkable harm to human health and often reason great mortality. In the past years humanity has undergone infection by MERS-CoV (Middle East respiratory syndrome), SARS-CoV (severe acute respiratory syndrome), and COVID-19 coronaviruses, which are spread from animals to humans then from person to person. These days COVID-19, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly spread around the world, becoming a global health emergency. Determined by increased interleukin IL-2, (IL)-6, IL-10, IL-7, granulocyte-colony stimulating factor (G-CSF),macro-phage inflammatory protein 1α (MIP1A), interferon- γ(IFNγ), and tumor necrosis factor-α(TNF-α), were found in patients with severe corona virus disease. Extensive changes in these cytokines are related to the prognosis and severity of the disease. Cytokine storm Cause of high numerous ofmortality in patients admitted to hospital with COVID-19 viral pneumonia. Therefor treatment of cytokine storm syndrome (CSS) has been challenging as underlying the etiology of rescuing severe COVID-19. Several of the cytokines in COVID-19 employ a different intracellular signaling pathway mediated by Janus kinases (JAKs). Recent studies have determined that at least two variants in the tyrosine kinase 2(TYK2) are associated with covid-19 disease. These variants may affect host inflammatory cytokines production so the cytokine storm triggers acute respiratory distress syndrome (ARDS) in theworst case scenario. TYK2 belongs to the JAK protein tyrosine kinase family and immuno regulatory cytokines (type I and type III IFNs, IL-22, IL-23, IL-10, IL-12,) in immune and non-immune cells. More specifically TYK2 has been associated with several autoimmune diseases (AIDs) and inflammatory diseases.Here, we have studied one common TYK2 variant: rs2304256, a non-synonymous variant that causes a valine to phenylalanine substitution in exon 8 (c.1084 G > T, Val362Phe).In addition Preliminary studies have shown that microRNA can mediate an intracellular defense mechanism against several RNA viruses. According to bioinformatics database hsa-miR-1283and rs2304256 which related TYK2 gene was selected to study the Coronavirus disease, thensearching in different databases like NCBI, mirwalk, mirBASE, DAVID to achieve our goals. In the current paper we found that a lower level of hsa-miR1283and emphasizing recent research understanding that miRNA(miR-1283) that directly target the potential factors related pathways i.e., JAK/STAT in COVID-19 in addition the importance of mature microRNA typically as a cellular defense mechanism against pathogenic coronavirus infections. So, it has beensuggested that rs2304256 reduces TYK2 function, resulting in a decreased susceptibility to IFN-related immune diseases and finally this will help to understand the interplay of hsa-miR- 556-3p within foremost signaling pathways and develop multifactorial approach to treat COVID-19.

Keywords:

bioinformatics , covid-19 , has-miR-1283 , rs2304256