ArticleMolecules (Basel, Switzerland)2020
A Novel Purification Procedure for Active Recombinant Human DPP4 and the Inability of DPP4 to Bind SARS-CoV-2.
Article in Molecules (Basel, Switzerland), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Disentangling conflicting evidence on DPP-4 inhibitors and outcomes of COVID-19: narrative review and meta-analysis.Journal of endocrinological investigation · 2021Pooled it
- The role of DPP4 in viral infections: from receptor biology to antiviral target.Archives of virology · 2026Review
- Targeting Gut Microbiota by DPP-4 Inhibitors in Obesity: Mechanistic Insights and Therapeutic Implications.Current nutrition reports · 2026Review
- A Novel Fibroblast Activation Protein-Based Algorithm to Assess Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease.Journal of gastroenterology and hepatology · 2026Article
- Role of the DPP4 Receptor in SARS-CoV Entry: Insights From Docking and Molecular Dynamics Simulations.Proteins · 2025Article
- An RGD motif on SARS-CoV-2 Spike induces TGF-β signaling and downregulates interferon.Journal of virology · 2025Article
- A Facile Method for Screening DPP IV Inhibitors in Living Cell System Based on Enzyme Activity Probe.Journal of analytical methods in chemistry · 2025Article
- ACE2-Fc and DPP4-Fc decoy receptors against SARS-CoV-2 and MERS-CoV variants: a quick therapeutic option for current and future coronaviruses outbreaks.Antibody therapeutics · 2024Article
- Immunologic and inflammatory consequences of SARS-CoV-2 infection and its implications in renal disease.Frontiers in immunology · 2024Review
- Role of Dipeptidyl Peptidase-4 (DPP4) on COVID-19 Physiopathology.Biomedicines · 2022Review
- Going viral in the islet: mediators of SARS-CoV-2 entry beyond ACE2.Journal of molecular endocrinology · 2022Review
- The enzymes in COVID-19: A review.Biochimie · 2022Review
- Proline-specific peptidase activities (DPP4, PRCP, FAP and PREP) in plasma of hospitalized COVID-19 patients.Clinica chimica acta; international journal of clinical chemistry · 2022Article
- Human Identical Sequences, hyaluronan, and hymecromone ─ the new mechanism and management of COVID-19.Molecular biomedicine · 2022Review
- Review
- Article
- Decreased circulating dipeptidyl peptidase-4 enzyme activity is prognostic for severe outcomes in COVID-19 inpatients.Biomarkers in medicine · 2022Observational
- Increased complications of COVID-19 in people with cardiovascular disease: Role of the renin-angiotensin-aldosterone system (RAAS) dysregulation.Chemico-biological interactions · 2022Review
- Diabetes and SARS-CoV-2-Is There a Mutual Connection?Frontiers in cell and developmental biology · 2022Review
- Characterization and comparison of novel adjuvants for a prefusion clamped MERS vaccine.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
18 authors at 2 institutions in 1 country.
Funding
Abstract
Proteases catalyse irreversible posttranslational modifications that often alter a biological function of the substrate. 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. Understanding protein structure and function requires reliable protocols for production and purification. We developed such strategies for baculovirus generated soluble recombinant human DPP4 (residues 29-766) produced in insect cells. Purification used differential ammonium sulphate precipitation, hydrophobic interaction chromatography, dye affinity chromatography in series with immobilised metal affinity chromatography, and ion-exchange chromatography. 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.