sitagliptin-phosphate and Pneumonia--Viral

Recently, an outbreak of a fatal coronavirus, SARS-CoV-2, has emerged from China and is rapidly spreading worldwide. Possible interaction of SARS-CoV-2 with DPP4 peptidase may partly contribute to the viral pathogenesis. An integrative bioinformatics approach starting with mining the biomedical literature for high confidence DPP4-protein/gene associations followed by functional analysis using network analysis and pathway enrichment was adopted. The results indicate that the identified DPP4 networks are highly enriched in viral processes required for viral entry and infection, and as a result, we propose DPP4 as an important putative target for the treatment of COVID-19. Additionally, our protein-chemical interaction networks identified important interactions between DPP4 and sitagliptin. We conclude that sitagliptin may be beneficial for the treatment of COVID-19 disease, either as monotherapy or in combination with other therapies, especially for diabetic patients and patients with pre-existing cardiovascular conditions who are already at higher risk of COVID-19 mortality.

Topics: Cardiovascular Diseases; Computational Biology; Coronavirus Infections; COVID-19; Crystallography, X-Ray; Data Mining; Diabetes Complications; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Drug Delivery Systems; Drug Repositioning; Gene Regulatory Networks; Humans; Molecular Structure; Pandemics; Pneumonia, Viral; Sitagliptin Phosphate

No Abstract.

Topics: Angiotensin-Converting Enzyme 2; Betacoronavirus; Coronavirus Infections; COVID-19; Cytokines; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Drug Repositioning; Humans; Inflammation; Lung; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; SARS-CoV-2; Sitagliptin Phosphate

Patients with SARS-CoV-2 infections experience lymphopenia and inflammatory cytokine storms in the severe stage of the disease, leading to multi-organ damage. The exact pattern of immune system changes and their condition during the disease process is unclear. The available knowledge has indicated that the NF-kappa-B pathway, which is induced by several mediators, has a significant role in cytokine storm through the various mechanisms. Therefore, identifying the state of the immune cells and the dominant mechanisms for the production of cytokines incorporated in the cytokine storm can be a critical step in the therapeutic approach. On the other hand, some studies identified a higher risk for diabetic patients. Diabetes mellitus exhibits a close association with inflammation and increases the chance of developing COVID-19. Patients with diabetes mellitus have shown to have more virus entry, impaired immunity response, less viral elimination, and dysregulated inflammatory cytokines. The parallel analysis of COVID-19 and diabetes mellitus pathogenesis has proposed that the control of the inflammation through the interfering with the critical points of major signaling pathways may provide the new therapeutic approaches. In recent years, the role of Dipeptidyl Peptidase 4 (DPP4) in chronic inflammation has been proved. Numerous immune cells express the DPP4 protein. DPP4 regulates antibody production, cytokine secretion, and immunoglobulin class switching. DPP4 inhibitors like sitagliptin reduce inflammation intensity in different states. Following the accumulating data, we hypothesize that sitagliptin might reduce COVID-19 severity. Sitagliptin, an available DPP4 inhibitor drug, showed multidimensional anti-inflammatory effects among diabetic patients. It reduces the inflammation mostly by affecting on NF-kappa-B signaling pathway. Under the fact that inflammatory mediators are active in individuals with COVID-19, blocking the predominant pathway could be helpful.

Topics: Coronavirus Infections; COVID-19; COVID-19 Drug Treatment; Cytokines; Diabetes Complications; Diabetes Mellitus; Dipeptidyl Peptidase 4; Humans; Inflammation; Insulin Resistance; Models, Theoretical; NF-kappa B p50 Subunit; Pandemics; Pneumonia, Viral; Signal Transduction; Sitagliptin Phosphate

Poor outcomes have been reported in patients with type 2 diabetes and coronavirus disease 2019 (COVID-19); thus, it is mandatory to explore novel therapeutic approaches for this population.. In a multicenter, case-control, retrospective, observational study, sitagliptin, an oral and highly selective dipeptidyl peptidase 4 inhibitor, was added to standard of care (e.g., insulin administration) at the time of hospitalization in patients with type 2 diabetes who were hospitalized with COVID-19. Every center also recruited at a 1:1 ratio untreated control subjects matched for age and sex. All patients had pneumonia and exhibited oxygen saturation <95% when breathing ambient air or when receiving oxygen support. The primary end points were discharge from the hospital/death and improvement of clinical outcomes, defined as an increase in at least two points on a seven-category modified ordinal scale. Data were collected retrospectively from patients receiving sitagliptin from 1 March through 30 April 2020.. Of the 338 consecutive patients with type 2 diabetes and COVID-19 admitted in Northern Italy hospitals included in this study, 169 were on sitagliptin, while 169 were on standard of care. Treatment with sitagliptin at the time of hospitalization was associated with reduced mortality (18% vs. 37% of deceased patients; hazard ratio 0.44 [95% CI 0.29-0.66];. In this multicenter, case-control, retrospective, observational study of patients with type 2 diabetes admitted to the hospital for COVID-19, sitagliptin treatment at the time of hospitalization was associated with reduced mortality and improved clinical outcomes as compared with standard-of-care treatment. The effects of sitagliptin in patients with type 2 diabetes and COVID-19 should be confirmed in an ongoing randomized, placebo-controlled trial.

Topics: Betacoronavirus; Coronavirus; Coronavirus Infections; COVID-19; Diabetes Mellitus, Type 2; Hospitalization; Humans; Italy; Pandemics; Pneumonia, Viral; Retrospective Studies; SARS-CoV-2; Sitagliptin Phosphate

Topics: Betacoronavirus; Coronavirus Infections; COVID-19; Diabetes Mellitus, Type 2; Hospitalization; Humans; Pandemics; Pneumonia, Viral; Retrospective Studies; SARS-CoV-2; Sitagliptin Phosphate