J Endocrinol Metab
Journal of Endocrinology and Metabolism, ISSN 1923-2861 print, 1923-287X online, Open Access
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Editorial

Volume 10, Number 2, April 2020, pages 35


Can Dipeptidyl Peptidase 4 Inhibitor Be the Therapeutic Candidate for the COVID-19?

Hidekatsu Yanaia, b, c

aDepartment of Diabetes, Endocrinology and Metabolism, National Center for Global Health and Medicine Kohnodai Hospital, Chiba, Japan
bDepartment of Internal Medicine, National Center for Global Health and Medicine Kohnodai Hospital, 1-7-1 Kohnodai, Ichikawa, Chiba 272-8516, Japan
cCorresponding Author: Hidekatsu Yanai, Department of Internal Medicine, National Center for Global Health and Medicine Kohnodai Hospital, 1-7-1 Kohnodai, Ichikawa, Chiba 272-8516, Japan

Manuscript submitted April 19, 2020, accepted April 27, 2020
Short title: DPP4 and the COVID-19
doi: https://doi.org/10.14740/jem641

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19) has reached a pandemic level. There is an urgent need for effective treatment. Dipeptidyl peptidase 4 (DPP4; also known as cluster of differentiation 26 (CD26)) was identified as a functional receptor for the Middle East respiratory syndrome coronavirus (MERS-CoV) [1]. It has been speculated that the preferential spatial localization of DPP4 in alveolar regions may explain why MERS is characterized by lower respiratory tract diseases [2], and such characteristic was also observed in COVID-19. The S1 domain of SARS-CoV-2 spike glycoprotein potentially interacts with the human CD26, a key immunoregulatory factor for hijacking and virulence [3].

The widespread expression of DPP4 on blood vessels, myocardium, and myeloid cells and function of CD26 as a signaling and binding protein suggest a crucial role in cardiovascular regulation and inflammation [4]. DPP4 is upregulated in proinflammatory states such as obesity, diabetes and atherosclerotic diseases [4]. In a recent retrospective cohort study of COVID-19, comorbidities were present in nearly half of patients, with hypertension (30%) being the most common comorbidity, followed by diabetes (19%) and coronary artery disease (8%) [5]. In univariable analysis, odds of in-hospital death were significantly higher in patients with diabetes (2.85) or coronary artery disease (21.40) [5]. DPP4 inhibitor is the most commonly used oral antidiabetic drug, and its safety is excellent. The sub-analysis of COVID-19 retrospective cohort studies which evaluate the influence of DPP4 inhibitor use on severity, morbidity and mortality in diabetic patients may assist in the development of new therapeutics for COVID-19.

Acknowledgments

None to declare.

Financial Disclosure

None to declare.

Conflict of Interest

None to declare.

Author Contributions

HY wrote and approved the final paper.

Data Availability

The author declares that data supporting the findings of this study are available within the article.


References▴Top 
  1. Raj VS, Mou H, Smits SL, Dekkers DH, Muller MA, Dijkman R, Muth D, et al. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature. 2013;495(7440):251-254.
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  2. Meyerholz DK, Lambertz AM, McCray PB, Jr. Dipeptidyl Peptidase 4 Distribution in the Human Respiratory Tract: Implications for the Middle East Respiratory Syndrome. Am J Pathol. 2016;186(1):78-86.
    doi pubmed
  3. Vankadari N, Wilce JA. Emerging WuHan (COVID-19) coronavirus: glycan shield and structure prediction of spike glycoprotein and its interaction with human CD26. Emerg Microbes Infect. 2020;9(1):601-604.
    doi pubmed
  4. Zhong J, Maiseyeu A, Davis SN, Rajagopalan S. DPP4 in cardiometabolic disease: recent insights from the laboratory and clinical trials of DPP4 inhibition. Circ Res. 2015;116(8):1491-1504.
    doi pubmed
  5. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054-1062.
    doi


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