Effect of Thalidomide on Kinases Implicated in Immune Response and MAPK signaling
The kinase screening assay identified key kinases involved in the regulation of immune response are functionally modulated by thalidomide. The most kinase affected was LCK and SYK (Figure 2C), critical modulators of T cell receptor signaling. Many LCK substrates, SPI1, TBK1, FOXP3, EGR1, ESR1, IRF1, CBL and STAT1 as well as SYK phosphorylation targets such as OAS1 and MX1 were up-regulated in SARS-coV-2 lung. Various processes mediating immune response including JUN phosphorylation, IKappaB phosphorylation, JAK-STAT pathway, leukocyte mediated immunity, neutrophil degranulation and activation, B cell receptor signaling and MAPK cascade were found to be affected by thalidomide (Figure 2D). PharmMapper results showed strong affinity for LCK, HCK and SYK along with other proteins involved in innate and adaptive immune response (Table S2, S3, S4). We studied the effects of thalidomide and its derivatives on endothelium and identified the down-regulation of several angiogenic genes (Figure S5 and Table S1).