Fig. 4
From: SARS-CoV-2 early infection signature identified potential key infection mechanisms and drug targets
Potential SARS-CoV-2 infection mechanism influencing potential drug choices for repurposing. The SARS-CoV-2 virus enters the cells through ACE2 receptors facilitated by TMPRSS2 and ADAM17. Drug molecules inhibiting the ACE2/TMPRSS2 axis dampen viral entry into the cell. Angiotensin II also activates JAK/STAT pathways upregulating proinflammatory cytokines. IL-1, TNF-α cytokines are mediators of innate immunity to stimulate an early innate response. These cytokines activate growth factor receptor pathways, such as PI3K/AKT and MAPK pathways leading to increased proinflammatory cytokines production via the NF-kB transcription factor. Therefore, JAK/STAT, PI3K/AKT and MAPK inhibitors may be beneficial in preventing inappropriate immune response. Inflammatory chemokines such as CXCL2, CXCL3, CCL20 attract other immune cell types to fight the infection and repair tissue damage leading to local tissue inflammation and cytokine storm. Glucocorticoids may help immune response associated with cytokine storm. G-protein coupled receptors, including bradykinin receptors and purinergic receptors, are also associated with SARS-CoV-2 infection