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Epi -Cyclophellitol Cyclosulfate, a Mechanism-Based Endoplasmic Reticulum α-Glucosidase II Inhibitor, Blocks Replication of SARS-CoV-2 and Other Coronaviruses.

التفاصيل البيبلوغرافية
العنوان: Epi -Cyclophellitol Cyclosulfate, a Mechanism-Based Endoplasmic Reticulum α-Glucosidase II Inhibitor, Blocks Replication of SARS-CoV-2 and Other Coronaviruses.
المؤلفون: Thaler M; Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands., Ofman TP; Leiden Institute of Chemistry, Leiden University, 2311 EZ Leiden, The Netherlands., Kok K; Leiden Institute of Chemistry, Leiden University, 2311 EZ Leiden, The Netherlands., Heming JJA; Leiden Institute of Chemistry, Leiden University, 2311 EZ Leiden, The Netherlands., Moran E; Department of Chemistry, University of York, York YO10 5DD, United Kingdom., Pickles I; Department of Chemistry, University of York, York YO10 5DD, United Kingdom., Leijs AA; Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands., van den Nieuwendijk AMCH; Leiden Institute of Chemistry, Leiden University, 2311 EZ Leiden, The Netherlands., van den Berg RJBHN; Leiden Institute of Chemistry, Leiden University, 2311 EZ Leiden, The Netherlands., Ruijgrok G; Leiden Institute of Chemistry, Leiden University, 2311 EZ Leiden, The Netherlands., Armstrong Z; Leiden Institute of Chemistry, Leiden University, 2311 EZ Leiden, The Netherlands., Salgado-Benvindo C; Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands., Ninaber DK; Department of Pulmonology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands., Snijder EJ; Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands., van Boeckel CAA; Leiden Institute of Chemistry, Leiden University, 2311 EZ Leiden, The Netherlands., Artola M; Leiden Institute of Chemistry, Leiden University, 2311 EZ Leiden, The Netherlands., Davies GJ; Department of Chemistry, University of York, York YO10 5DD, United Kingdom., Overkleeft HS; Leiden Institute of Chemistry, Leiden University, 2311 EZ Leiden, The Netherlands., van Hemert MJ; Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
المصدر: ACS central science [ACS Cent Sci] 2024 Jul 25; Vol. 10 (8), pp. 1594-1608. Date of Electronic Publication: 2024 Jul 25 (Print Publication: 2024).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: ACS Publications Country of Publication: United States NLM ID: 101660035 Publication Model: eCollection Cited Medium: Print ISSN: 2374-7943 (Print) Linking ISSN: 23747943 NLM ISO Abbreviation: ACS Cent Sci Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Washington DC : ACS Publications, [2015]-
مستخلص: The combined inhibition of endoplasmic reticulum (ER) α-glucosidases I and II has been shown to inhibit replication of a broad range of viruses that rely on ER protein quality control. We found, by screening a panel of deoxynojirimycin and cyclitol glycomimetics, that the mechanism-based ER α-glucosidase II inhibitor, 1,6- epi -cyclophellitol cyclosulfate, potently blocks SARS-CoV-2 replication in lung epithelial cells, halting intracellular generation of mature spike protein, reducing production of infectious progeny, and leading to reduced syncytium formation. Through activity-based protein profiling, we confirmed ER α-glucosidase II inhibition in primary airway epithelial cells, grown at the air-liquid interface. 1,6- epi -Cyclophellitol cyclosulfate inhibits early pandemic and more recent SARS-CoV-2 variants, as well as SARS-CoV and MERS-CoV. The reported antiviral activity is comparable to the best-in-class described glucosidase inhibitors, all competitive inhibitors also targeting ER α-glucosidase I and other glycoprocessing enzymes not involved in ER protein quality control. We propose selective blocking ER-resident α-glucosidase II in a covalent and irreversible manner as a new strategy in the search for effective antiviral agents targeting SARS-CoV-2 and other viruses that rely on ER protein quality control.
Competing Interests: The authors declare no competing financial interest.
(© 2024 The Authors. Published by American Chemical Society.)
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تواريخ الأحداث: Date Created: 20240902 Latest Revision: 20240903
رمز التحديث: 20240903
مُعرف محوري في PubMed: PMC11363342
DOI: 10.1021/acscentsci.4c00506
PMID: 39220688
قاعدة البيانات: MEDLINE
الوصف
تدمد:2374-7943
DOI:10.1021/acscentsci.4c00506