Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for Coronavirus Disease 2019 (COVID-19) pandemic. Cell entry of the virus can be mediated by several enzymes, such as ACE-2, DPP4/CD26, and TMPRSS2, upon viral membrane fusion through SARS-CoV-2 envelope spike glycoproteins. In docked molecular complexes, DPP4/CD26 functional receptors and viral spike proteins have a large interface, potentially leading to inflammation in severe COVID-19.
Objective: The aim of this study is to review the role of DPP4/CD26 in the immune system and its effects on the production of cytokine storms in COVID-19. Furthermore, we hypothesize that targeting DPP4/CD26 as a therapeutic strategy could reduce the inflammatory complications of SARS-CoV-2 infection.
Methods: The current review was conducted using keywords such as COVID-19, SARS-CoV-2, dipeptidyl peptidase-4, CD26, cytokine storm, and treatment to search for articles in Google Scholar and PubMed databases that were specifically oriented towards our objectives.
Results: The regulation or inhibition of DPP4/CD26 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 regard, the applications of DPP4/CD26 inhibitors, DPP4/CD26 siRNAs, and CD26 antibodies have been demonstrated to prevent cytokine storms and airway inflammation.
Conclusion: 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.
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