A review of Janus kinase inhibitors for the treatment of Covid-19 pneumonia

Abstract

Abstract Background In inflamed tissue, immune cells are accumulated, and various intercellular signals are involved in the pathogenesis. Janus kinases (JAKs) are typical tyrosine kinases involved in mediating the signaling of multiple cytokines and growth factors and induce the transcription of molecules related to inflammation or immunity via the transcription factor signal transducers and activators of transcription (STAT). Hence, they have garnered significant interest as a therapeutic target. JAK inhibitors have been evaluated as a major drug for remission induction in the treatment of autoimmune diseases such as rheumatoid arthritis. Body Covid-19 infection due to SARS-CoV-2 has caused a pandemic, with approximately 660 million infections and 6.7 million deaths worldwide (January, 2023). The prognosis is poor and the major causes of death are respiratory failure attributed to rapid pneumonia, thromboembolism due to a cytokine storm, and multi-organ failure. As a treatment modality, molecular targeted therapy, such as cytokine-targeting therapy, is attracting attention, in addition to antiviral drugs. Baricitinib, a JAK inhibitor, is used for the treatment of severe pneumonia, in addition to antiviral drugs and glucocorticoids. The mechanism of action of baricitinib includes inhibition of viral receptor-mediated endocytosis, which involves the NF-κB activating kinase (NAK) family, and mediating the anti-cytokine effects via JAK 1/2 inhibition. It improves severe pneumonia and reduces mortality. Conclusion Thus, the development of molecular targeted drugs with elucidated pathological mechanisms may aid in controlling Covid-19 infection.

Keywords

• SARS-CoV-2
• Covid-19
• treatment
• JAK
• baricitinib
• NAK family