دورية أكاديمية
Luminescent reporter cells enable the identification of broad-spectrum antivirals against emerging viruses.
العنوان: | Luminescent reporter cells enable the identification of broad-spectrum antivirals against emerging viruses. |
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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.) |
References: | Murray CJ, Lopez AD, Chin B, Feehan D, Hill KH. Estimation of potential global pandemic influenza mortality on the basis of vital registry data from the 1918-20 pandemic: a quantitative analysis. Lancet. 2006;368:2211-2218. Yun NE, Walker DH. Pathogenesis of Lassa fever. Viruses. 2012;4:2031-2048. Sahin U, Muik A, Derhovanessian E, et al. COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses. Nature. 2020;586:594-599. Nguyen HT, Zhang S, Wang Q, et al. Spike glycoprotein and host cell determinants of SARS-CoV-2 entry and cytopathic effects. J Virol. 2021;95(5):e02304-20. Bestle D, Heindl MR, Limburg H, et al. TMPRSS2 and furin are both essential for proteolytic activation of SARS-CoV-2 in human airway cells. Life Sci Alliance. 2020;3:e202000786. Hoffmann M, Kleine-Weber H, Pöhlmann S. A multibasic cleavage site in the spike protein of SARS-CoV-2 is essential for infection of human lung cells. Mol Cell. 2020;78:779-784. Seidah NG, Pasquato A, Andréo U. How do enveloped viruses exploit the secretory proprotein convertases to regulate infectivity and spread? Viruses. 2021;13:1229. Hay BA, Abrams B, Zumbrunn AY, et al. Aminopyrrolidineamide inhibitors of site-1 protease. Bioorg Med Chem Lett. 2007;17:4411-4414. Urata S, Yun N, Pasquato A, Paessler S, Kunz S, de la Torre JC. Antiviral activity of a small-molecule inhibitor of arenavirus glycoprotein processing by the cellular site 1 protease. J Virol. 2011;85:795-803. Pasquato A, Rochat C, Burri DJ, Pasqual G, la Torre JC, Kunz S. Evaluation of the anti-arenaviral activity of the subtilisin kexin isozyme-1/site-1 protease inhibitor PF-429242. Virology. 2012;423:14-22. Douglas LEJ, Reihill JA, Ho MWY, et al. A highly selective, cell-permeable furin inhibitor BOS-318 rescues key features of cystic fibrosis airway disease. Cell Chem Biol. 2022;29:947-957. Essalmani R, Jain J, Susan-Resiga D, et al. Distinctive roles of furin and TMPRSS2 in SARS-CoV-2 infectivity. J Virol. 2022;96:e0012822. Hardes K, Becker GL, Lu Y, et al. Novel furin inhibitors with potent anti-infectious activity. ChemMedChem. 2015;10:1218-1231. Hawkins JL, Robbins MD, Warren LC, et al. Pharmacologic inhibition of site 1 protease activity inhibits sterol regulatory element-binding protein processing and reduces lipogenic enzyme gene expression and lipid synthesis in cultured cells and experimental animals. J Pharmacol Exp Ther. 2008;326:801-808. Couture F, Kwiatkowska A, Dory YL, Day R. Therapeutic uses of furin and its inhibitors: a patent review. Expert Opin Ther Pat. 2015;25:379-396. da Palma JR, Burri DJ, Oppliger J, et al. Zymogen activation and subcellular activity of subtilisin kexin isozyme 1/site 1 protease. J Biol Chem. 2014;289:35743-35756. da Palma JR, Cendron L, Seidah NG, Pasquato A, Kunz S. Mechanism of folding and activation of subtilisin kexin Isozyme-1 (SKI-1)/Site-1 protease (S1P). J Biol Chem. 2016;291:2055-2066. Löw K, Hardes K, Fedeli C, et al. A novel cell-based sensor detecting the activity of individual basic proprotein convertases. FEBS J. 2019;286:4597-4620. Oppliger J, da Palma JR, Burri DJ, et al. A molecular sensor to characterize arenavirus envelope glycoprotein cleavage by subtilisin kexin isozyme 1/site 1 protease. J Virol. 2016;90:705-714. Ahmed R, Salmi A, Butler LD, Chiller JM, Oldstone MB. Selection of genetic variants of lymphocytic choriomeningitis virus in spleens of persistently infected mice. Role in suppression of cytotoxic T lymphocyte response and viral persistence. J Exp Med. 1984;160:521-540. Rojek JM, Pasqual G, Sanchez AB, Nguyen NT, de la Torre JC, Kunz S. Targeting the proteolytic processing of the viral glycoprotein precursor is a promising novel antiviral strategy against arenaviruses. J Virol. 2010;84:573-584. Rojek JM, Sanchez AB, Nguyen NT, de la Torre JC, Kunz S. Different mechanisms of cell entry by human-pathogenic Old World and New World arenaviruses. J Virol. 2008;82:7677-7687. Dutko FJ, Oldstone MBA. Genomic and biological variation among commonly used lymphocytic choriomeningitis virus strains. J Gen Virol. 1983;64(pt 8):1689-1698. Buchmeier MJ, Lewicki HA, Tomori O, Oldstone MBA. Monoclonal antibodies to lymphocytic choriomeningitis and pichinde viruses: generation, characterization, and cross-reactivity with other arenaviruses. Virology. 1981;113:73-85. Kerber R, Rieger T, Busch C, et al. Cross-species analysis of the replication complex of Old World arenaviruses reveals two nucleoprotein sites involved in L protein function. J Virol. 2011;85:12518-12528. Weber EL, Buchmeier MJ. Fine mapping of a peptide sequence containing an antigenic site conserved among arenaviruses. Virology. 1988;164:30-38. Zhang H, Fischer DK, Shuda M, et al. Construction and characterization of two SARS-CoV-2 minigenome replicon systems. J Med Virol. 2022;94:2438-2452. Wernike K, Hoffmann B, Kalthoff D, König P, Beer M. Development and validation of a triplex real-time PCR assay for the rapid detection and differentiation of wild-type and glycoprotein E-deleted vaccine strains of Bovine herpesvirus type 1. J Virol Methods. 2011;174:77-84. Kunz S, Edelmann KH, de la Torre JC, Gorney R, Oldstone MBA. Mechanisms for lymphocytic choriomeningitis virus glycoprotein cleavage, transport, and incorporation into virions. Virology. 2003;314:168-178. Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181:271-280. Neuhaus V, Danov O, Konzok S, et al. Assessment of the cytotoxic and immunomodulatory effects of substances in human precision-cut lung slices. J Vis Exp. 2018;135:57042. Zhang JH, Chung TDY, Oldenburg KR. A simple statistical parameter for use in evaluation and validation of high throughput screening assays. SLAS Discovery. 1999;4:67-73. Beyer WR, Pöpplau D, Garten W, von Laer D, Lenz O. Endoproteolytic processing of the lymphocytic choriomeningitis virus glycoprotein by the subtilase SKI-1/S1P. J Virol. 2003;77:2866-2872. Lenz O, ter Meulen J, Klenk HD, Seidah NG, Garten W. The Lassa virus glycoprotein precursor GP-C is proteolytically processed by subtilase SKI-1/S1P. Proc Natl Acad Sci USA. 2001;98:12701-12705. Wright K. Post-translational processing of the glycoproteins of lymphocytic choriomeningitis virus. Virology. 1990;177:175-183. Seidah N, Mayer G, Zaid A, et al. The activation and physiological functions of the proprotein convertases. Int J Biochem Cell Biol. 2008;40:1111-1125. Seidah NG, Prat A. The biology and therapeutic targeting of the proprotein convertases. Nat Rev Drug Discovery. 2012;11:367-383. Gao X, Zhang S, Gou J, et al. Spike-mediated ACE2 down-regulation was involved in the pathogenesis of SARS-CoV-2 infection. J Infect. 2022;85:418-427. Lu Y, Zhu Q, Fox DM, Gao C, Stanley SA, Luo K. SARS-CoV-2 down-regulates ACE2 through lysosomal degradation. Mol Biol Cell. 2022;33:ar147. Dai W, Zhang B, Jiang XM, et al. Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease. Science. 2020;368:1331-1335. Fischer 2nd, WA, Eron Jr, JJ, Holman W, et al. A phase 2a clinical trial of molnupiravir in patients with COVID-19 shows accelerated SARS-CoV-2 RNA clearance and elimination of infectious virus. Sci Transl Med. 2022;14:eabl7430. Jin Z, Du X, Xu Y, et al. Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors. Nature. 2020;582:289-293. Yin W, Mao C, Luan X, et al. Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir. Science. 2020;368:1499-1504. Zhang L, Lin D, Sun X, et al. Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors. Science. 2020;368:409-412. Fätkenheuer G, Pozniak AL, Johnson MA, et al. Efficacy of short-term monotherapy with maraviroc, a new CCR5 antagonist, in patients infected with HIV-1. Nat Med. 2005;11:1170-1172. Pullikotil P, Benjannet S, Mayne J, Seidah NG. The proprotein convertase SKI-1/S1P. J Biol Chem. 2007;282:27402-27413. Chapman HD, Jeffers TK, Williams RB. Forty years of monensin for the control of coccidiosis in poultry. Poult Sci. 2010;89:1788-1801. Mollenhauer HH, James Morré D, Rowe LD. Alteration of intracellular traffic by monensin; mechanism, specificity and relationship to toxicity. Biochim Biophys Acta Rev Biomembr. 1990;1031:225-246. Feliciangeli SF, Thomas L, Scott GK, et al. Identification of a pH sensor in the furin propeptide that regulates enzyme activation. J Biol Chem. 2006;281:16108-16116. Kuismanen E, Saraste J, Pettersson RF. Effect of monensin on the assembly of Uukuniemi virus in the Golgi complex. J Virol. 1985;55:813-822. Rivinoja A, Hassinen A, Kokkonen N, Kauppila A, Kellokumpu S. Elevated Golgi pH impairs terminal N-glycosylation by inducing mislocalization of Golgi glycosyltransferases. J Cell Physiol. 2009;220:144-154. Ono M, Mannen K, Shimada T, Kuwano V, Mifune K. Effect of monensin on the synthesis, maturation and secretion of vesicular stomatitis virus proteins in a monensin-resistant Chinese hamster ovary cell line. Cell Struct Funct. 1985;10:279-294. Ju X, Zhu Y, Wang Y, et al. A novel cell culture system modeling the SARS-CoV-2 life cycle. PLoS Pathog. 2021;17:e1009439. Svenningsen EB, Thyrsted J, Blay-Cadanet J, et al. Ionophore antibiotic X-206 is a potent inhibitor of SARS-CoV-2 infection in vitro. Antiviral Res. 2021;185:104988. Xiao X, Wang C, Chang D, et al. Identification of potent and safe antiviral therapeutic candidates against SARS-CoV-2. Front Immunol. 2020;11:586572. Johnson BA, Xie X, Bailey AL, et al. Loss of furin cleavage site attenuates SARS-CoV-2 pathogenesis. Nature. 2021;591:293-299. Peacock TP, Goldhill DH, Zhou J, et al. The furin cleavage site in the SARS-CoV-2 spike protein is required for transmission in ferrets. Nat Microbiol. 2021;6:899-909. Dyall J, Coleman CM, Hart BJ, et al. Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection. Antimicrob Agents Chemother. 2014;58:4885-4893. Carette JE, Raaben M, Wong AC, et al. Ebola virus entry requires the cholesterol transporter Niemann-Pick C1. Nature. 2011;477:340-343. Flint M, Chatterjee P, Lin DL, et al. A genome-wide CRISPR screen identifies N-acetylglucosamine-1-phosphate transferase as a potential antiviral target for Ebola virus. Nat Commun. 2019;10:285. Jan JT, Cheng TJR, Juang YP, et al. Identification of existing pharmaceuticals and herbal medicines as inhibitors of SARS-CoV-2 infection. Proc Natl Acad Sci USA. 2021;118:e2021579118. |
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 |
تدمد: | 1096-9071 |
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DOI: | 10.1002/jmv.29211 |