As the incidence of COVID-19 increases with time, more and more efforts are made to pave a way out for the therapeutic strategies to deal with the disease progression. Inflammation being a significant influencer has implicated us to re-look into its signaling cascades drawing attention towards the JAK/STAT pathway. Considered as a major signaling mediator of cytokines and chemokines, the JAK/STAT pathway has significantly contributed to the worsening of COVID-19. JAK phosphorylation mediated by cytokine receptor activation leads to phosphorylation of STATs that translocate into the nucleus to translate for inflammatory mediators. The SARS-CoV-2 infection triggers the inflammation via the JAK/STAT pathway mainly through its structural and non-structural proteins leading towards the development of cytokine storms. This produces various inflammatory markers in the host that determine the disease severity. Therefore, inhibiting JAK/STAT signaling with JAK/STAT inhibitors like Ruxolitinib, Baricitinib, Tofacitinib could hamper the inflammatory cascade and reduce inflammation. Even though they are implicated with multiple adverse effects, the regulatory authorities have supported its use, and numerous clinical trials are in progress to prove their safety and efficacy. On the contrary, the exact mechanism of JAK/STAT inhibition at molecular levels remains to be speculative for which further investigations are required.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.