Table 1.

Summarized effects of sDPP4-targeted agents reported in preclinical and clinical research.

Agents	Preclinical data		Previous clinical trials	COVID-19
	Cells	Animal models		Ongoing clinical trials
Gliptins	•Block MERS-CoV infection in macrophages [110]. •Prevention of sDPP4-induced hVSMC proliferation and inflammation [45].	•Prevention of sDPP4-induced endothelial dysfunction in mice [46]. •Anti-oxidant effects in STZ-induced diabetic rats and LPS-induced sepsis mouse model, respectively [80,111]. •Reduction of NLRP3/ASC inflammasome activation in db/db mice [81]. •Improved cardiac function in mice [82].	•Decreased risk of non-fatal CV events and CV mortality [76]. •No risk of infection in type 1 and type 2 diabetic patients [86]. •Increased cardio and vasculoprotective substrates [28,78,79]. •Anti-inflammatory effects in type 2 dibatec patients [67,69]. •Improved flow-mediated vasodilation in diabetic patients [83]. •Potential induction of leucopenia, angioedema, cough and asthma [97,98].	•SIDIACO Sitagliptin (NCT04365517) •Linagliptin: NCT04371978, NCT04341935
sDPP4	•Block MERS-CoV infection in Vero cells [87]. •hVSMC proliferation and inflammation [45]. •Pro-inflammatory effects [45,46]. •Inhibition of T-cell activation and proliferation via ADA binding [101].	•Endothelial dysfunction in murine mesenteric microvessels [46]. •Increased monocyte migration in LDLR−/− mice [112].		•Direct truncation of CCL5/RANTES: reduced IL-6 levels and viremia (Iwata et al., 1999; Patterson et al., 2020)
AntiDPP4 vaccine	•Blockade of MERS-CoV infection [107]. •No effects on T-cell proliferation or cytokine production [106].	•Increased GLP-1 in type 1 and type 2 diabetic mice [104,105].