Fig. 1.

The possible mechanisms of baricitinib on cytokine storm caused by SARS-CoV-2.

When the human body is invaded by SARS-CoV-2, the immune system will release a large number of cytokines (such as IFN-γ, IL-6 etc.). Excessive amounts of cytokines bind to their receptors and activates JAKs, which occurs upon ligand-mediated receptor multimerization. The activated JAK phosphorylates the receptor, activates and phosphorylates its main substrate STATs. For example, IFN-γ signals via JAK1 and JAK2 which in turn activate STAT1, whereas IL-6 can signal via JAK1, JAK2, and/or TYK2 and activates STAT3. Phosphorylated STAT dimerizes with other members of STAT family. Then, the dimerized STATs in the cytoplasm are transferred into the nucleus and combine to specific DNA elements to regulate the expression of cytokine-responsive genes. Subsequently, cytokine storm was finally induced.