دورية أكاديمية
أعرض في EDS

Luminescent reporter cells enable the identification of broad-spectrum antivirals against emerging viruses.

التفاصيل البيبلوغرافية
العنوان: Luminescent reporter cells enable the identification of broad-spectrum antivirals against emerging viruses.
المؤلفون: Löw K; Department of Biochemistry & Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, Hannover, Germany.; Institute of Microbiology, University Hospital Center and University of Lausanne, Lausanne, Switzerland., Möller R; Department of Biochemistry & Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, Hannover, Germany., Stegmann C; Department of Biochemistry & Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, Hannover, Germany., Becker M; Department of Biochemistry & Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, Hannover, Germany., Rehburg L; Department of Biochemistry & Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, Hannover, Germany., Obernolte H; Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Hannover, Germany.; Fraunhofer International Consortium for Anti-Infective Research (iCAIR), Hannover, Germany.; Fraunhofer Cluster of Excellence Immune-Mediated Diseases, (CIMD), Hannover, Germany.; Member of the German Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive Lung Disease (BREATH) Research Network, Hannover, Germany.; Institute of Immunology, Hannover Medical School, Hannover, Germany., Schaudien D; Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Hannover, Germany.; Fraunhofer International Consortium for Anti-Infective Research (iCAIR), Hannover, Germany.; Fraunhofer Cluster of Excellence Immune-Mediated Diseases, (CIMD), Hannover, Germany.; Member of the German Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive Lung Disease (BREATH) Research Network, Hannover, Germany.; Institute of Immunology, Hannover Medical School, Hannover, Germany., Oestereich L; Department of Virology, Bernhard-Nocht Institute for Tropical Medicine, Hamburg, Germany.; German Center for Infectious Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Hamburg., Braun A; Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Hannover, Germany.; Fraunhofer International Consortium for Anti-Infective Research (iCAIR), Hannover, Germany.; Fraunhofer Cluster of Excellence Immune-Mediated Diseases, (CIMD), Hannover, Germany.; Member of the German Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive Lung Disease (BREATH) Research Network, Hannover, Germany.; Institute of Immunology, Hannover Medical School, Hannover, Germany., Kunz S; Institute of Microbiology, University Hospital Center and University of Lausanne, Lausanne, Switzerland., Gerold G; Department of Biochemistry & Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, Hannover, Germany.; Department of Clinical Microbiology, Umeå University, Sweden.; Wallenberg Centre for Molecular Medicine (WCMM), Umeå University, Sweden.
المصدر: Journal of medical virology [J Med Virol] 2023 Nov; Vol. 95 (11), pp. e29211.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Wiley-Liss Country of Publication: United States NLM ID: 7705876 Publication Model: Print Cited Medium: Internet ISSN: 1096-9071 (Electronic) Linking ISSN: 01466615 NLM ISO Abbreviation: J Med Virol Subsets: MEDLINE
أسماء مطبوعة: Publication: New York Ny : Wiley-Liss
Original Publication: New York, Liss.
مواضيع طبية MeSH: Furin*/metabolism , Arenavirus*/genetics , Arenavirus*/metabolism, Humans ; Viral Envelope Proteins/genetics ; Monensin/metabolism ; Monensin/pharmacology ; Antiviral Agents/therapeutic use
مستخلص: The emerging viruses SARS-CoV-2 and arenaviruses cause severe respiratory and hemorrhagic diseases, respectively. The production of infectious particles of both viruses and virus spread in tissues requires cleavage of surface glycoproteins (GPs) by host proprotein convertases (PCs). SARS-CoV-2 and arenaviruses rely on GP cleavage by PCs furin and subtilisin kexin isozyme-1/site-1 protease (SKI-1/S1P), respectively. We report improved luciferase-based reporter cell lines, named luminescent inducible proprotein convertase reporter cells that we employ to monitor PC activity in its authentic subcellular compartment. Using these sensor lines we screened a small compound library in high-throughput manner. We identified 23 FDA-approved small molecules, among them monensin which displayed broad activity against furin and SKI-1/S1P. Monensin inhibited arenaviruses and SARS-CoV-2 in a dose-dependent manner. We observed a strong reduction in infectious particle release upon monensin treatment with little effect on released genome copies. This was reflected by inhibition of SARS-CoV-2 spike processing suggesting the release of immature particles. In a proof of concept experiment using human precision cut lung slices, monensin potently inhibited SARS-CoV-2 infection, evidenced by reduced infectious particle release. We propose that our PC sensor pipeline is a suitable tool to identify broad-spectrum antivirals with therapeutic potential to combat current and future emerging viruses.
(© 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)
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معلومات مُعتمدة: German Federal Ministry for Education and Research; Niedersächsisches Ministerium für Wissenschaft und Kultur; Knut and Allice Wallenberg foundation; Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
فهرسة مساهمة: Keywords: SARS-CoV-2; SKI-1/S1P; antiviral; arenavirus; broad-spectrum; emerging virus; furin; high-throughput screening; inducible sensor cell lines; inhibition; pandemic preparedness; proprotein convertase; viral GP cleavage
المشرفين على المادة: EC 3.4.21.75 (Furin)
0 (Viral Envelope Proteins)
906O0YJ6ZP (Monensin)
0 (Antiviral Agents)
تواريخ الأحداث: Date Created: 20231117 Date Completed: 20231127 Latest Revision: 20231208
رمز التحديث: 20240628
DOI: 10.1002/jmv.29211
PMID: 37975336
قاعدة البيانات: MEDLINE
الوصف
تدمد:1096-9071
DOI:10.1002/jmv.29211