Evaluation of DPP4/CD26 Potential Role for the Management of Inflammation in COVID-19 Patients

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the recent Coronavirus Disease 2019 (COVID-19) pandemic, mainly transmitting through respiratory droplets. The primary mechanism of viral infection is associated with SARS-CoV-2 envelope spike glycoproteins. Upon membrane fusion, viral entry is mediated by several enzymes, such as ACE-2, DPP4/CD26, and TMPRSS2. In docked molecular complexes, DPP4/CD26 functional receptors and viral spike proteins have a large interface, potentially leading to inflammation in severe COVID-19. Thus, its regulation or inhibition might affect one or more stages in COVID-19 immuno- pathogenesis due to its associations with many immunological functions, such as modulating the NF-kB pathway, upregulating CD86 expression, activating proliferation of T cells, and influencing the antiviral response and cytokine storm in COVID-19. In this study, we reviewed the role of DPP4/CD26 in the immune system and its effects on the production of cytokine storms in COVID-19. Furthermore, we hypothesized that targeting DPP4/CD26 as a therapeutic strategy could reduce the inflammatory complications of SARS-CoV-2 infection. In this regard, the applications of DPP4/CD26 inhibitors, DPP4/CD26 siRNAs, and CD26 antibodies have been demonstrated to prevent cytokine storms and airway inflammation. At last, it is suggested to utilize novel technologies such as CRISPR/Cas and chimeric antigen receptor T cells, based on their many advantages, to increase the sensitivity and specificity of future treatment methods.