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. 2023 Mar 20;14:1135145. doi: 10.3389/fphar.2023.1135145

FIGURE 3.

FIGURE 3

Plausible mechanism of Jakinibs in COVID-19 (Baricitinib as prototype drug): Jakinibs inhibit viral entry and intracellular assembly of virus in target cells by inhibiting AAK1 and GAK-dependent receptor-mediated endocytosis. Furthermore, Jakinibs inhibit various JAKs proteins, suppressing the phosphorylation and nuclear translocation of STAT proteins and downregulating the transcription of cytokine genes. Thus, Jakinibs suppress the release of various pro-inflammatory cytokines (Cytokine storm; IL-6, IL-12, IFN-γ, and GM-CSF) and subsequent immune dysregulation, alleviating hyperinflammation state and ARDS in COVID-19 patients. (Abbreviations- SARS-CoV-2, severe acute respiratory syndrome-coronavirus-2; ACE-2, angiotensin-converting enzyme-2; GAK, cyclin G-associated kinase; AAK1, AK1 adaptor protein-associated kinase 1; JAK, Janus kinase; STAT, signal transducer and activator of transcription; ALI, acute lung injury; ARDS, acute respiratory distress syndrome; COVID-19, Coronovirus-2019 disease).