Figure 3. DPP-4 inhibitors targeting TLR4 mediated immunopathogenesis of COVID-19. DPP-4 inhibitors mediated therapeutic strategies to target human TLR4, NF-κB, ERK, NLR-P3/ASC and T-cell activation against SARS-CoV-2 and to protect multiorgan damage.

The anti-DPP-4 drug sitagliptin can directly binds to TLR4 to inhibit the downstream inflammatory cascade while alogliptin inhibits ERK which is one of crucial the downstream signaling mediator originated of TLR4 signaling pathway. In direct inhibitory effects of the gliptins on the T cell-induced secretion of the pro-inflammatory cytokines has also been presented. These inhibitory actions could be useful in mitigating the cytokine storm in the COVID-19 patients. Inhibition of ERK plays useful role in limiting the effects of the MMPs on the blood vessels and also blocks the activation of AP-1 mediated synthesis of the inflammatory molecules. Linagliptin has inhibitory effects on the NLRP3-mediated activation of IL-1β which in turn prevents cardiac inflammation in COVID-19 patients.