dipeptidyl peptidase 4

Gene Context Sentence

Table 2. Analysis of context sentence of DPP4 gene in 59 abstracts.

PMID Gene Context Sentence
32199615 Intriguingly, we found that the candidate co-receptors, manifesting the most similar expression patterns with ACE2 across 13 human tissues, are all peptidases, including ANPEP, DPP4 and ENPEP. […] Among them, ANPEP and DPP4 are the known receptors for human CoVs, suggesting ENPEP as another potential receptor for human CoVs.
32265331 In this study, we evaluated parainfluenza virus 5 (PIV5)-based vaccine expressing the MERS-CoV envelope spike protein (PIV5/MERS-S) in a human DPP4 knockin C57BL/6 congenic mouse model (hDPP4 KI). […] Following a single-dose intranasal immunization, PIV5-MERS-S induced neutralizing antibody and robust T cell responses in hDPP4 KI mice.
32294179 Two coronavirus receptor proteins, Angiotensin Converting Enzyme 2 (ACE2) and Dipeptidyl Peptidase-4 (DPP4) are also established transducers of metabolic signals and pathways regulating inflammation, renal and cardiovascular physiology, and glucose homeostasis. […] Moreover, glucose-lowering agents such as the DPP4 inhibitors, widely used in subjects with T2D, are known to modify the biological activities of multiple immunomodulatory substrates. […] Here we review the basic and clinical science spanning the intersections of diabetes, coronavirus infections, ACE2, and DPP4 biology, highlighting clinical relevance and evolving areas of uncertainty underlying the pathophysiology and treatment of T2D in the context of coronavirus infection.
32335097 It has been hypothesized that DPP4 inhibition, a therapy currently available for type 2 diabetes, might represent a target for decreasing the risk of the acute respiratory complications of the COVID-19 infection but (1) lack of demonstration of SARS-CoV2 binding to DPP4 (2) possible protective role of sDPP4 in Middle East respiratory Syndrome (MERS-CoV) (3) demonstrated inhibition and downregulation of DPP4 by HIV1 and MERS-CoV and (4) not exclusive role of the receptor binding in tropism of the Coronavirus family, support that DPP4 inhibition at present doesn’t represent a plausible approach to mitigate COVID-19.
32336007 Dipeptidyl peptidase 4 (DPP4), also known as cluster of differentiation 26 (CD26), is a serine exopeptidase expressed ubiquitously in several tissues, including but not limited to lung, kidney, liver, gut, and immune cells. […] The question has been raised on whether DPP4 modulation or inhibition may prevent infection and/or progression of the COVID-19. […] A docked complex model of the SARS-CoV-2 spike glycoprotein and DPP4 has been proposed, showing a large interface between the proteins and proposing close similarity with other coronaviruses using DPP4 as functional receptor. […] Nevertheless, this observation may rise the question on whether DPP4 is directly involved in SARS-CoV-2 cell adhesion/virulence, and whether DPP4 inhibition might be a therapeutic strategy for preventing infection. […] Although a direct involvement of DPP4 in SARS-CoV-2 infection needs to be clarified, there is also evidence suggesting that DPP4i modulate inflammation and exert anti-fibrotic activity. […] Taken together these findings may suggest a potential role for DPP4 inhibition or modulation in one or more steps of COVID-19 immunopathogenesis.
32338224 In the case of MERS-CoV, S proteins bind to the host cell receptor dipeptidyl peptidase 4 (DPP4 or CD26) which is broadly expressed on intestinal, alveolar, renal, hepatic and prostate cells as well as on activated leukocytes [8]. […] In the case of MERSCoV, its RBM binds to DPP4 with residues 484-567, thus, suggesting that its RBD differs from that of SARS-CoV [12, 13].
32349031 In this article, we are focusing on the impact of ACE inhibitors (ACEI) and DPP4 inhibitors used on SARS-CoV-2 activity and discussions about those drugs that may be related to infectious condition of COVID-19 diseases.
32374427 In this study, a total of 38 conjunctival samples from 38 patients, including 12 healthy conjunctiva, 12 melanoma, 7 squamous cell carcinoma and 7 papilloma samples, were analyzed using high-throughput RNA sequencing to assess mRNA expression of the SARS-CoV-2 receptor ACE2 and its cofactors including TMPRSS2, ANPEP, DPP4, and ENPEP.
32394639 Cell binding and entry of betacoronaviruses is via their surface spike glycoprotein; SARS-CoV binds to the metalloprotease angiotensin-converting enzyme 2 (ACE2), MERS-CoV utilizes dipeptidyl peptidase 4 (DPP4), and recent modeling of the structure of SARS-CoV-2 spike glycoprotein predicts that it can interact with human DPP4 in addition to ACE2. […] DPP4 is a ubiquitous membrane-bound aminopeptidase that circulates in plasma; it is multifunctional with roles in nutrition, metabolism, and immune and endocrine systems. […] DPP4 activity differentially regulates glucose homeostasis and inflammation via its enzymatic activity and nonenzymatic immunomodulatory effects. […] The importance of DPP4 for the medical community has been highlighted by the approval of DPP4 inhibitors, or gliptins, for the treatment of type 2 diabetes mellitus. […] This review discusses the dysregulation of DPP4 in COVID-19 comorbid conditions; DPP4 activity is higher in older individuals and increased plasma DPP4 is a predictor of the onset of metabolic syndrome. […] DPP4 upregulation may be a determinant of COVID-19 disease severity, which creates interest regarding the use of gliptins in management of COVID-19. […] Also, knowledge of the chemistry and biology of DPP4 could be utilized to develop novel therapies to block viral entry of some betacoronaviruses, potentially including SARS-CoV-2.
32405622 Here, bioinformatics approaches combining human-virus protein interaction prediction and protein docking based on crystal structures have revealed the high affinity between human dipeptidylpeptidase 4 (DPP4) and the spike (S) receptor-binding domain of SARS-CoV-2. […] Intriguingly, the crucial binding residues of DPP4 are identical to those that are bound to the MERS-CoV-S. […] Moreover, E484 insertion and adjacent substitutions should be most essential for this DPP4-binding ability acquirement of SARS-CoV-2-S compared with SARS-CoV-S. […] This potential utilization of DPP4 as a binding target for SARS-CoV-2 may offer novel insight into the viral pathogenesis and help the surveillance and therapeutics strategy for meeting the challenge of COVID-19.
32425249 As such, no available evidence has yet suggested that glucose-lowering drugs - including those targeting DPP4-related pathways - produce any significant harm or benefit in the context of human infections.
32456064 Even more relevant, and irrespective of glucose-lowering activities, DPP4 inhibitors and GLP1 receptor agonists may have a favorable impact on the modulation of viral entry and overproduction of inflammatory cytokines during COVID-19 infection, although current evidence is limited and not univocal.
32463365 We find the gut as the putative hotspot of COVID-19, where a maturation correlated transcriptional signature is shared in small intestine enterocytes among coronavirus receptors(ACE2, DPP4, ANPEP).
32471607 As such, no available evidence has yet suggested that glucose-lowering drugs - including those targeting DPP4-related pathways - produce any significant harm or benefit in the context of human infections.
32495299 It has been recently observed that dipeptidyl peptidase-4 (DPP4), the receptor for MERS-CoV (Middle East respiratory syndrome-related coronavirus) and ACE2 have similar expression profiles in the lung. […] DPP4 has important metabolic and immune functions and is a target for commonly used therapies in T2D.
32496587 We performed RNA sequencing and explored available RNA-Seq databases to study gene expression and co-expression of ACE2, CD147 (BSG), CD26 (DPP4) and their direct and indirect molecular partners in primary human bronchial epithelial cells, bronchial and skin biopsies, bronchoalveolar lavage fluid, whole blood, peripheral blood mononuclear cells (PBMCs), monocytes, neutrophils, DCs, NK cells, ILC1, ILC2, ILC3, CD4+ and CD8+ T cells, B cells and plasmablasts. […] ACE2 and TMPRSS2 were coexpressed at the epithelial sites of the lung and skin, whereas CD147 (BSG), cyclophilins (PPIA and PPIB), CD26 (DPP4) and related molecules were expressed in both, epithelium and in immune cells.
32506195 Virus binds to the cell surface receptor ACE2; indeed, recent evidences suggested that SARS-CoV-2 may be using as co-receptor, when entering the cells, the same one used by MERS-Co-V, namely the DPP4/CD26 receptor. […] The aforementioned observation underlined that mechanism of cell entry is supposedly similar among different coronavirus, that the co-expression of ACE2 and DPP4/CD26 could identify those cells targeted by different human coronaviruses and that clinical complications may be similar. […] The DPP4 family/system was implicated in various physiological processes and diseases of the immune system, and DPP4/CD26 is variously expressed on epithelia and endothelia of the systemic vasculature, lung, kidney, small intestine and heart. […] In particular, DPP4 distribution in the human respiratory tract may facilitate the entrance of the virus into the airway tract itself and could contribute to the development of cytokine storm and immunopathology in causing fatal COVID-19 pneumonia. […] The use of DPP4 inhibitors, such as gliptins, in patients with COVID-19 with, or even without, type 2 diabetes, may offer a simple way to reduce the virus entry and replication into the airways and to hamper the sustained cytokine storm and inflammation within the lung in patients diagnosed with COVID-19 infection.
32574272 Virus protein ligands (e.g., haemagglutinin or trimeric spike glycoprotein for Influenza and CoV, respectively) interact with cellular receptors, such as (depending on the virus) either sialic acids, Dipeptidyl peptidase 4 (DPP4), or angiotensin-converting enzyme 2 (ACE2).
32592113 Furthermore, dipeptidyl peptidase 4 (DPP4) enzyme is highly expressed in the lung, and that it may have additional actions besides its effects on glucose metabolism, which might exert profound pro-inflammatory effects. […] We briefly review the impact on the inflammatory system of DPP4 for its possible detrimental effect on COVID-19 syndrome, and of DPP4 inhibitors (gliptins), currently used as glucose lowering agents, which may have the potential to exert positive pleiotropic effect on inflammatory diseases, in addition to their effects on glucose metabolism.
32615317 Some highly expressed genes in both short- and long-term models played a crucial role in the progression of SARS-CoV/SARS-CoV-2 infection, including DPP4, BMP2, NFIA, AXIN2, DAAM1, ZNF608, ME1, MGLL, LGR4, ABHD6, and ACADM.
32618198 It has been hypothesized that the human dipeptidyl peptidase 4 (DPP4) enzyme receptor may be a functional target for the spike proteins of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). […] Since DPP4-inhibitors are currently used for the treatment of patients with type-2 diabetes (T2DM), there is currently high interest in the possibility that these agents, or incretin-based therapies (IBTs) in general, may be of benefit against the new coronavirus infection.
32635752 MERS coronavirus uses DPP4, while coronavirus HCoV-NL63 and SARS-CoV and SARS-CoV-2 employ ACE-2 as the key receptor.
32661206 Cellular receptor ACE2, serine protease TMPRSS2 and exopeptidase CD26 (also known as DPP4) are the three membrane bound proteins potentially implicated in SARS-CoV-2 infection.
32679426 Like SARS-CoV-1, SARS-CoV-2 exploits the ACE2 receptors to enter the host cells; nevertheless, recent bioinformatics insights suggest a potential interaction of SARS-CoV-2 with the «moonlighting protein» CD26/DPP4, exactly how MERS-CoV works. […] CD26/DPP4 is overexpressed on T-helper type 1 (Th1) cells and its expression increases with aging, all factors which could well explain the Th1 immune lockdown, especially in the elderly, during fatal SARS-CoV-2 infections.
32721805 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. […] Sitagliptin, an available DPP4 inhibitor drug, showed multidimensional anti-inflammatory effects among diabetic patients.
32838195 Secondly, DPP4 receptor involvement in the putative viral entry of SARS-CoV-2 may be prevented by DPP4i.
32848769 In silico experiments proposed that SARS-CoV-2 might bind dipeptidyl peptidase 4 (DPP4/CD26), which was established previously as receptor for MERS-CoV. […] The renin-angiotensin-aldosterone system (RAAS) component ACE2 and DPP4 are proteins dysregulated in diabetes. […] Imbalance of the RAAS and direct effect of soluble DPP4 exert deleterious vascular effects. […] We hypothesize that diabetic patients might be more affected by COVID-19 due to increased presence ACE2 and DPP4 mediating infection and contributing to a compromised vasculature. […] Here, we discuss the role of ACE2 and DPP4 as relevant factors linking the risk of SARS-CoV-2 infection and severity of COVID-19 in diabetic patients and present an outlook on therapeutic potential of current drugs targeted against RAAS and DPP4 to treat or prevent COVID-19-derived vascular complications.
32867305 We analyzed 131 COVID-19 patients by exome sequencing and examined the genetic variants of TMPRSS2, PCSK3, DPP4, and BSG genes.
32897211 These ingredients activate renin-angiotensin system signaling pathway and apoptosis signaling pathway by regulating 10 protein targets (ACE, ACE2, AGTR1, FURIN, TNF, CASP3, CASP6, DPP4, MCL1 and POLD1) to execute 42 biological functions such as renin-angiotensin regulation of blood volume and systemic arterial blood pressure to treat COVID-19.
32902372 Through computational analyses, we have identified homologous genomic regions within the ORF1ab and S genes that could facilitate recombination, and have analysed co-expression patterns of the cellular receptors for SARS-CoV-2 and MERS-CoV, ACE2 and DPP4, respectively, to identify human anatomical sites that could facilitate co-infection.
32909925 Mouse DPP4 (mDPP4) receptor is not a functional receptor for MERS-CoV while human DPP4 (hDPP4) is, despite the high similarities between hDPP4 and mDPP4 receptors. […] The variability of DPP4 receptors against MERS-CoV is not fully investigated, especially conformational and structural differences. […] Therefore, investigating the conformational differences of the DPP4 receptors can aid in developing new small animal models for MERS-CoV vaccines and antiviral agents evaluation. […] Here we used MD simulations and docking techniques to investigate these structural differences in DPP4 receptors. […] The results showed chimeric mouse mDPP4 (cmDPP4) has a similar compact conformation as wild-type hDPP4 based on the structural analysis. […] Interestingly, a single Thr288Ala mutation induced a relaxed conformation in chimeric 2 hDPP4 (c2hDPP4) and chimeric 2 mDPP4 (c2mDPP4); in addition to its significant effect on the DPP4 flexibility. […] Moreover, MERS-CoV RBD adopts a “standing” conformation when docked to hDPP4 and cmDPP4 in blade IV and V regions. […] In conclusion, the results could explain the functionality differences between mouse and human DPP4 receptors against MERS-CoV. […] However, further structural studies are needed to evaluate how DPP4 conformations affects MERS-CoV RBD binding and affinity.
32912711 An expansive literature search using keywords: “COVID-19”, “SARS-CoV-2”, “diabetes”, “type 2 diabetes’’,”type 1 diabetes“,”ACE2“,”polymorphism“,”DPP4" and “telemedicine” was conducted on Pubmed and EMBASE till 7th August 2020.
32970391 Here, the expression of five genes, known to encode coronavirus receptors/interactors (ACE2, TMPRSS2, CLEC4M, DPP4 and TMPRSS11D), was investigated in normal and cancer tissues, and their molecular relationships with clinical comorbidities were investigated. […] Their expression levels were found to be significantly altered in cancer types, including colon, kidney, liver, testis, thyroid and skin cancers (P < 0.0001); AUC > 0.80 suggests that TMPRSS2, CLEC4M and DPP4 are relevant markers of kidney, liver, and thyroid cancer, respectively.
32974224 DPP4 expressed on human cells is the main attaching site for RBD in S protein of MERS CoV.
32974340 Other coronavirus family receptors (ANPEP and DPP4) were also expressed in the first and second trimester placental cells. […] Additionally, the term placenta of multiple species including humans expressed ACE2, DPP4, and ANPEP along with the viral S protein proteases.
32975064 Additionally, the expression levels of some probable co-receptors, including dipeptidyl peptidase 4 (DPP4), aminopeptidase N (AMPN), and glutamyl aminopeptidase (AMPE), were unchanged in the affected UC, CD, intestinal BD, and intestinal TB colon mucosa samples.
32984489 It is proposed that a high Kmucin is the cost for subsequent binding of MERS-CoV to SAs on the cell surface to partially overcome the unfavourable entropy of immobilisation as the virus adopts the correct orientation for spike protein interactions with its protein cellular receptor DPP4.
33013423 Lung immunoblot analysis of smokers, COPD and IPF subjects revealed increased abundance of proteases and receptor/spike protein like TMPRSS2, furin, and DPP4 in association with a slight increase in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor ACE2 levels. […] Overall, these findings suggest that altered transcription of target genes that regulate mitochondrial function, cellular senescence, and telomere attrition in the pathobiology of lung aging in COPD and IPF is associated with alterations in SARS-CoV-2 ACE2-TMPRSS2-Furin-DPP4 axis as pharmacological targets for COVID-19.
33024851 We collect the nasopharyngeal and oropharyngeal swabs of 63 subjects with severe symptoms or contacts with COVID-19 confirmed cases to perform a pilot-study aimed to verify the “in situ” expression of SARS-CoV-2 host invasion genes (ACE2, TMPRSS2, PCSK3, EMILIN1, EMILIN2, MMRN1, MMRN2, DPP4). […] ACE2 (FC = +1.88, p ≤ 0.05) and DPP4 (FC = +3, p < 0.01) genes showed a significant overexpression in COVID-19 patients. […] ACE2 and DPP4 expression levels had a good performance (AUC = 0.75; p < 0.001) in distinguishing COVID-19 patients from negative subjects. […] Interestingly, we found a significant positive association of ACE2 mRNA and PCSK3, EMILIN1, MMRN1 and MMRN2 expression and of DPP4 mRNA and EMILIN2 expression only in COVID-19 patients. […] Noteworthy, a subgroup of severe COVID-19 (n = 7) patients, showed significant high level of ACE2 mRNA and another subgroup of less severe COVID-19 patients (n = 6) significant raised DPP4 levels. […] These results indicate that a group of SARS-CoV-2 host invasion genes are functionally related in COVID-19 patients and suggests that ACE2 and DPP4 expression level could act as genomic biomarkers. […] Moreover, at the best of our knowledge, this is the first study that shows an elevated DPP4 expression in naso- and oropharyngeal swabs of COVID-19 patient thus suggesting a functional role of DPP4 in SARS-CoV-2 infections.
33026922 Recent studies have revealed that both SARS CoV and SARS-CoV-2 invade target cells through a membrane-bound angiotensin-convert enzyme 2 (ACE2), an important component of the renin-angiotensin system (RAS) which maintains human homeostasis, whereas MERS utilizes host cells’ receptor dipeptidyl peptidase 4 (DPP4) for entry.
33046644 Of concern, rSADS-CoV also replicated efficiently in several different primary human lung cell types, as well as primary human intestinal cells. rSADS-CoV did not use human coronavirus ACE-2, DPP4, or CD13 receptors for docking and entry.
33101175 In the past two hitherto similar CoVs, the severe acute respiratory syndrome CoV (SARS-CoV-1) and Middle East respiratory syndrome CoV (MERS-CoV) also gained universal attention as they produced clinical symptoms similar to those of SARS-CoV-2 utilizing angiotensin-converting enzyme 2 (ACE2) receptor and dipeptidyl peptidase 4 (DPP4) to go into the cells.
33151168 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.
33188364 Angiotensin-converting enzyme 2 (ACE2), which is part of the renin-angiotensin-aldosterone system (RAAS), is the main entry receptor for SARS-CoV-2; although dipeptidyl peptidase 4 (DPP4) might also act as a binding target. […] Preliminary data, however, do not suggest a notable effect of glucose-lowering DPP4 inhibitors on SARS-CoV-2 susceptibility.
33205807 It has been reported that T-cell regulatory dipeptidyl peptidase 4 (DPP4; cluster of differentiation 26 (CD26)) binds to the external spike (S) glycoprotein of SARS-CoV-2 as a receptor, for the viral entry into the host cell.
33218025 The protease dipeptidyl peptidase 4 (DPP4) is a pharmacological target in type 2 diabetes therapy primarily because it inactivates glucagon-like protein-1. […] DPP4 also has roles in steatosis, insulin resistance, cancers and inflammatory and fibrotic diseases. […] In addition, DPP4 binds to the spike protein of the MERS virus, causing it to be the human cell surface receptor for that virus. […] DPP4 has been identified as a potential binding target of SARS-CoV-2 spike protein, so this question requires experimental investigation. […] We developed such strategies for baculovirus generated soluble recombinant human DPP4 (residues 29-766) produced in insect cells. […] The binding affinities of DPP4 to the SARS-CoV-2 full-length spike protein and its receptor-binding domain (RBD) were measured using surface plasmon resonance and ELISA. […] This optimised DPP4 purification procedure yielded 1 to 1.8 mg of pure fully active soluble DPP4 protein per litre of insect cell culture with specific activity >30 U/mg, indicative of high purity. […] No specific binding between DPP4 and CoV-2 spike protein was detected by surface plasmon resonance or ELISA. […] In summary, a procedure for high purity high yield soluble human DPP4 was achieved and used to show that, unlike MERS, SARS-CoV-2 does not bind human DPP4.
33233425 Among affected ACE2-network components connected with the SARS-Cov-2 interactome, we identified AGT (Angiotensinogen), CAT (Catalase), DPP4 (Dipeptidyl Peptidase 4), CCL2 (C-C Motif Chemokine Ligand 2), TFRC (Transferrin Receptor) and CAV1 (Caveolin-1), associated with cardiovascular risk factors.
33244381 The protein digestion and absorption as a significant pathway was highlighted with enriched genes of ACE2, MEP1A, MEP1B, DPP4, and XPNPEP2.
33254506 A recent study proved that coronavirus SARS-CoV-2 also uses dipeptidyl peptidase-4 (DPP4, also known as adenosine deaminase complexing protein 2, CD26) as a co-receptor when entering cells. […] In addition, DPP4 is also implicated in the regulation of the immune response. […] Thus, the combination of DPP4 inhibition and suppression of ACE-2/RAAS may be a novel therapeutic strategy for combating this pandemic.
33313148 Compared with the other coronavirus receptors, such as aminopeptidase N (ANPEP) or dipeptidyl peptidase 4 (DPP4), the mRNA and protein expression of ACE2 was increased in the heart.
33329052 We also describe the importance of the immune system, which is dysregulated in hypertension and SARS-CoV-2 infection, and the potential involvement of the multifunctional enzyme dipeptidyl peptidase 4 (DPP4), that, in addition to the angiotensin-converting enzyme 2 (ACE2), may contribute to the SARS-CoV-2 entrance into target cells.
33333995 The invasion-mechanism of SARS-CoV-2 and SARS-CoV, involves binding of its spike protein with angiotensin-converting enzyme 2 (ACE2) receptors; MERS-CoV utilizes dipeptidyl peptidase 4 (DPP4), whereas H1N1 influenza is equipped with hemagglutinin protein.
33344548 Dipeptidyl peptidase-4 (DPP4) is commonly targeted to achieve glycemic control and has potent anti-inflammatory and immunoregulatory effects. […] Recent structural analyses indicated a potential tight interaction between DPP4 and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), raising a promising hypothesis that DPP4 inhibitor (DPP4i) drugs might be an optimal strategy for treating coronavirus disease 2019 (COVID-19) among patients with diabetes. […] However, there has been no direct clinical evidence illuminating the associations between DPP4i use and COVID-19 outcomes. […] To illuminate the associations between DPP4i usage and the adverse outcomes of COVID-19. […] Finally, 111 participants treated with DPP4i drugs were successfully matched to 333 non-DPP4i users. […] Then, a linear logistic model and mixed-effect Cox model were applied to analyze the associations between in-hospital DPP4i use and adverse outcomes of COVID-19. , the median level of fasting blood glucose and random blood glucose) and inflammatory regulation was approximately equivalent in the DPP4i and non-DPP4i groups. […] Furthermore, we did not observe substantial side effects such as uncontrolled glycemia or acidosis due to DPP4i application relative to the use of non-DPP4i agents in the study cohort. […] Our findings demonstrated that DPP4i use is not significantly associated with poor outcomes of COVID-19 or other adverse effects of anti-diabetic treatment. […] The data support the continuation of DPP4i agents for diabetes management in the setting of COVID-19.
33413422 Lungs lacked the overexpression of ACE2 as suspected, however, high ACE2 but low DPP4 expression was observed in nasopharyngeal cells.
33512688 Studies have suggested that SARS-CoV-2 may bind dipeptidyl peptidase-4 (DPP4) for entering cells of the respiratory tract. […] Besides, DPP4 takes part in immune system regulation. […] Thus, DPP-4 inhibitors (DPP4i) may play a role against COVID-19. […] We focused on the impact of DPP4i treatment on COVID-19-related outcomes in people with DM. […] Retrospective observational studies provide inconsistent results on the association between use of DPP4i and outcomes of COVID-19. […] While two studies reported significantly lower mortality rates among patients with DM who received DPP4i versus those who did not, a series of other studies showed no effect of DPP4i or even worse outcomes. […] A meta-analysis of 7 studies yielded a neutral estimate of the risk ratio of COVID-19-related mortality among users of DPP4i (0.81; 95% CI 0.57-1.15). […] In the absence of randomized controlled trials, observational research available so far provides inconclusive results and insufficient evidence to recommend use of DPP4i against COVID-19.
33527308 Since DPP4 inhibitors, gliptins, are widely used in diabetes patients, the exact role of DPP4 modulation in SARS-CoV-2 infection, at least in that group, urgently needs to be clarified.
33550350 The 3D homologous modelling was performed by SWISS-MODEL to establish mutated S protein structural model, in which the protein-docking was then implemented with angiotensin-converting enzyme 2 (ACE2), dipeptidyl peptidase-4 (DPP4) and aminopeptidase N (APN) by ZDOCK, and the combining capacity of each mutated S protein evaluated by FiPD. […] Protein-receptor docking analysis between naturally mutated S protein and host receptors showed that, in the case of spontaneous mutation, the binding ability of S protein to ACE2 tended to be weakened, while the binding ability of DPP4 tended to be enhanced, and there was no significant change in the binding ability of APN. […] The mutated SARS-CoV-2 might tend to target human cells with DPP4 as a new receptor rather than keep ACE2 as its unique receptor for human infection.
33564056 In this study, we investigated the variability of four genes (ACE2, ANPEP and DPP4 encoding for host receptors of the viral spike proteins and TMPRSS2 encoding for a host proteinase) in 23 European (19 autochthonous and three commercial breeds and one wild boar population) and two Asian Sus scrofa populations.
33584268 Here, we review the role of antidiabetic agents, mainly including insulin, metformin, pioglitazone, dipeptidyl peptidase-4 (DPP4) inhibitors, sodium-glucose cotransporter 2 (SGLT2) inhibitors, and glucagon-like peptide 1 (GLP-1) receptor agonists in DM patients with coronavirus infection, addressing the clinical therapeutic choices for these subjects.