---
title: "Reduced DPP4 Binding Enables MERS‑CoV Resistance to Soluble DPP4 While Preserving Entry via High D"
id: "biorxiv-5-reduced-dpp4-binding-confers-resistance-to-soluble-dpp4-while-preserving-mers"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-5-reduced-dpp4-binding-confers-resistance-to-soluble-dpp4-while-preserving-mers"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.09.14.751648v1?rss=1"
published_at: "2026-09-20T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Reduced DPP4 Binding Enables MERS‑CoV Resistance to Soluble DPP4 While Preserving Entry via High D
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-5-reduced-dpp4-binding-confers-resistance-to-soluble-dpp4-while-preserving-mers
- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.09.14.751648v1?rss=1)
- **Published At:** 2026-09-20T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- The study used a vesicular stomatitis virus pseudotype encoding MERS‑CoV spike (VSV‑MERS‑S) to probe resistance to soluble recombinant **DPP4** (sDPP4). - Serial passaging of VSV‑MERS‑S in the presence of sDPP4 selected spike receptor‑binding‑domain (RBD) mutations at residue 507, specifically **L507I** and **L507H**. - These L507 substitutions reduced binding of sDPP4 and conferred measurable resistance to sDPP4 inhibition in cell culture. - Viruses bearing L507I/H maintained robust entry into cell lines expressing high levels of **DPP4**, but showed reduced entry into cells with low **DPP4** expression. - Additional naturally occurring polymorphisms at L507 (L507F/R/P) observed in patient‑derived sequences produced a stronger effect; **L507R** and **L507P** conferred complete resistance to sDPP4 in this model. - The findings indicate that decreased sDPP4 binding can be a mechanism of resistance while still allowing viral spread in tissues with abundant **DPP4**, with possible implications for therapeutic use of sDPP4 and for understanding viral polymorphisms. - Details on in vivo consequences, clinical correlates, and broader fitness costs beyond the in vitro entry assays were not reported in the source article.
## Clinical Analysis & Structured Key Points
Reduced DPP4 Binding Confers Resistance to Soluble DPP4 While Preserving MERS-CoV Entry into Cells Expressing High Levels of DPP4 | bioRxiv Skip to main content New Results Reduced DPP4 Binding Confers Resistance to Soluble DPP4 While Preserving MERS-CoV Entry into Cells Expressing High Levels of DPP4 Nianzhen Chen , View ORCID Profile Stefan H. Pöhlmann , Markus Hoffmann doi: https://doi.org/10.64898/2026.09.14.751648 Nianzhen Chen 1 German Primate Center - Leibniz Institute for Primate Research; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Stefan H. Pöhlmann 2 Deutsches Primatenzentrum GmbH - Leibniz-Institut fur Primatenforschung Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Stefan H. Pöhlmann For correspondence: spoehlmann{at}dpz.eu Markus Hoffmann 2 Deutsches Primatenzentrum GmbH - Leibniz-Institut fur Primatenforschung Find this author on Google Scholar Find this author on PubMed Search for this author on this site Abstract Info/History Metrics Preview PDF Abstract The Middle East respiratory syndrome coronavirus uses DPP4/CD26 as receptor for cell entry. Soluble recombinant DPP4 can block MERS-CoV infection in cell culture and in animal models and might hold promise as antiviral. Furthermore, endogenous soluble DPP4 in plasma might reduce MERS-CoV dissemination in infected individuals. Therefore, we addressed whether and how MERS-CoV can acquire resistance against soluble DPP4 (sDPP4), employing a vesicular stomatitis virus (VSV) encoding the MERS-CoV spike (S) protein (VSV-MERS-S). Passaging of VSV-MERS-S in the presence of sDPP4 selected for viral variants with mutations L507I and L507H in the receptor binding domain (RBD) of the S protein. These mutations reduced sDPP4 binding, were compatible with robust entry into cell lines expressing high levels of DPP4 and conferred sDPP4 resistance. In contrast, entry into cell lines expressing low levels of DPP4 was reduced. Furthermore, polymorphisms L507F/R/P, which were detected in MERS-CoV sequences from patients, exhibited an even more pronounced phenotype, with L507R and L507P conferring complete sDPP4 resistance. Collectively, our results show that naturally occurring polymorphisms in the MERS-CoV S protein can confer sDPP4 resistance by reducing sDPP4 binding but might still be compatible with robust viral spread in cells and tissues expressing high levels of DPP4. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license . Back to top Previous Next Posted September 20, 2026. Download PDF Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following Reduced DPP4 Binding Confers Resistance to Soluble DPP4 While Preserving MERS-CoV Entry into Cells Expressing High Levels of DPP4 Message Subject (Your Name) has forwarded a page to you from bioRxiv Message Body (Your Name) thought you would like to see this page from the bioRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share Reduced DPP4 Binding Confers Resistance to Soluble DPP4 While Preserving MERS-CoV Entry into Cells Expressing High Levels of DPP4 Nianzhen Chen , Stefan H. Pöhlmann , Markus Hoffmann bioRxiv 2026.09.14.751648; doi: https://doi.org/10.64898/2026.09.14.751648 Share This Article: Copy Citation Tools Reduced DPP4 Binding Confers Resistance to Soluble DPP4 While Preserving MERS-CoV Entry into Cells Expressing High Levels of DPP4 Nianzhen Chen , Stefan H. Pöhlmann , Markus Hoffmann bioRxiv 2026.09.14.751648; doi: https://doi.org/10.64898/2026.09.14.751648 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Areas All Articles Animal Behavior and Cognition (8013) Biochemistry (18739) Bioengineering (14888) Bioinformatics (44418) Biophysics (22599) Cancer Biology (19723) Cell Biology (26899) Clinical Trials (138) Developmental Biology (13965) Ecology (21005) Epidemiology (2067) Evolutionary Biology (25455) Genetics (16166) Genomics (23507) Immunology (18705) Microbiology (42503) Molecular Biology (18059) Neuroscience (93451) Paleontology (700) Pathology (2977) Pharmacology and Toxicology (5095) Physiology (8114) Plant Biology (15999) Scientific Communication and Education (2095) Synthetic Biology (4560) Systems Biology (10235) Zoology (2391)
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