The SARS-CoV-2 virus enters the cells by binding to Dipeptidyl peptidase-4. The dipeptidyl peptidase-4 (DPP-4) inhibitors have shown benefits in decreasing the mortality and severity associated with SARS–CoV-2 infection. DPP-4 has the potential to block the host CD26 receptor and modulate the DPP4/CD26 activity consequently restricting SARS–CoV-2 from entering the T cells. DPP-4 inhibitors including Gliptins, sDPP4 (soluble form), and AntiDPP4 vaccine is extensively used for the management of Type 2 diabetes mellitus. Gliptins improve endothelial function through their antioxidants, potentially having protective effects on the vascular system, and anti-inflammatory response.
In addition, gliptins also play a key role in inhibiting the binding of SARS-CoV-2 virus with the host cells. In diabetic patients, treatment with sitagliptin decreased the molecular markers of inflammation as IL-6 and CRP in mononuclear cells and circulating levels of IL-1b, IL-6, TNF-a, CRP, and intracellular adhesion molecules. Furthermore, in-vitro studies have shown that sDPP4 has a preventive effect on the formation of endogenous DPP4/CD26-ADA complexes in human macrophages/dendritic cells leading to inhibited proliferation and activation of T-cells. Anti-DPP4 vaccination is another therapeutic modality confirmed to control plasma DPP4 activity through the in-vitro model. This in turn can impede virus entry and coate cellular DPP4.
Thus, it can be concluded that DPP-4 inhibitors display antifibrotic, anti-inflammatory and immunomodulatory properties in addition to their confirmed antidiabetic activity. The use of DPP-4 inhibitors could reduce mortality due to COVID-19 or could improve the progression of the disease; this evidence may support the management of diabetic patients diagnosed with COVID-19; however, more investigation is needed.
Source: Metabolism Open
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