Figure 1.

Silibinin as a direct STAT3 inhibitor: regulating the response intensity of reactive reparative cells to damaged tissues. STAT3 is a master checkpoint regulator of the interface between cytokines, inflammation, and immune response against various types of tissue damage including viral infections. By operating as a direct inhibitor of STAT3, silibinin regulates the response intensity of reparative cells (e.g., macrophages, astrocytes) to damaged tissues (e.g., radiation-induced lung injury, primary lung tumor, brain metastasis). In the ongoing scenario of the 2019—2020 SARS-CoV-2 pandemic, in which the futile accumulation of inflammatory macrophages in lungs as the main source of pro-inflammatory cytokines associates with fatal disease in a subgroup of severe COVID-19 patients fully meeting acute respiratory distress syndrome (ARDS) criteria, targeted antagonism of STAT3 with silibinin might ameliorate COVID-19 morbidity and mortality.