European Training Network on Antiviral Drug Development

Rezultaty

PhD Thesis Titles & Degrees

List of PhD thesis titles and degrees

ANTIVIRALS website

Website with restricted area for internal affairs launched

ESR weblog

ESRs launch their own blog

International conference

One International Conference organised

Recruitment

All ESRs recruited and Declarations on Conformity submitted

Publikacje

Bithiazole Inhibitors of Phosphatidylinositol 4‐Kinase (PI4KIIIβ) as Broad‐Spectrum Antivirals Blocking the Replication of SARS‐CoV‐2, Zika Virus, and Human Rhinoviruses

Autorzy: Maria Grazia Martina; Ilaria Vicenti; Lisa Bauer; Emmanuele Crespan; Enrico Rango; Adele Boccuto; Noemi Olivieri; Matteo Incerti; Marleen Zwaagstra; Marika Allodi; Simona Bertoni; Elena Dreassi; Maurizio Zazzi; Frank J. M. Kuppeveld; Giovanni Maga; Marco Radi
Opublikowane w: Chemmedchem, Numer 5, 2021, ISSN 1860-7179
Wydawca: Wiley - V C H Verlag GmbbH & Co.
DOI: 10.1002/cmdc.202100483

Fluoxetine targets an allosteric site in the enterovirus 2C AAA+ ATPase and stabilizes a ring-shaped hexameric complex

Autorzy: DANIEL L. HURDISS, PRISCILA EL KAZZI, LISA BAUER, NICOLAS PAPAGEORGIOU, FRANÇOIS P. FERRON, TIM DONSELAAR, ARNO L.W. VAN VLIET, TATIANA M. SHAMORKINA, JOOST SNIJDER, BRUNO CANARD, ETIENNE DECROLY, ANDREA BRANCALE, TZVIYA ZEEV-BEN-MORDEHAI, FRIEDRICH FÖRSTER, FRANK J.M. VAN KUPPEVELD, BRUNO COUTARD
Opublikowane w: SCIENCE ADVANCES, 2022, ISSN 2375-2548
Wydawca: American Association for the Advancement of Science
DOI: 10.1126/sciadv.abj7615

Small-Molecule Inhibitors of Chikungunya Virus: Mechanisms of Action and Antiviral Drug Resistance.

Autorzy: Kristina Kovacikova; Martijn J. van Hemert
Opublikowane w: Antimicrobial Agents and Chemotherapy, Numer 1, 2020, ISSN 0066-4804
Wydawca: American Society for Microbiology
DOI: 10.1128/aac.01788-20

Rational design of highly potent broad-spectrum enterovirus inhibitors targeting the nonstructural protein 2C.

Autorzy: Lisa Bauer; Roberto Manganaro; Birgit Zonsics; Daniel L. Hurdiss; Marleen Zwaagstra; Tim Donselaar; Naemi G. E. Welter; Regina G.D.M. van Kleef; Moira Lorenzo Lopez; Federica Bevilacqua; Thamidur Raman; Salvatore Ferla; Marcella Bassetto; Johan Neyts; Jeroen R.P.M. Strating; Remco H.S. Westerink; Andrea Brancale; Frank J. M. van Kuppeveld
Opublikowane w: PLoS Biology, Numer Vol 18, Iss 11, p e3000904, 2020, ISSN 1544-9173
Wydawca: Public Library of Science
DOI: 10.1371/journal.pbio.3000904

Structure-function analysis of the nsp14 N7-guanine methyltransferase reveals an essential role in Betacoronavirus replication

Autorzy: Ogando, Natacha,; El Kazzi, Priscila; Zevenhoven-Dobbe, Jessika,; Bontes, Brenda,; Decombe, Alice; Posthuma, Clara,; Thiel, Volker; Canard, Bruno; Ferron, Francois; Decroly, Etienne; Snijder, Eric,
Opublikowane w: PNAS, Numer 7;118(49), 2021, ISSN 1091-6490
Wydawca: PNAS
DOI: 10.1073/pnas.2108709118

6'-β-Fluoro-Homoaristeromycin and 6'-Fluoro-Homoneplanocin A Are Potent Inhibitors of Chikungunya Virus Replication through Their Direct Effect on Viral Nonstructural Protein 1.

Autorzy: Kovacikova, Kristina; Morren, Bas M.; Tas, Ali; Albulescu, Irina C.; van Rijswijk, Robin; Jarhad, Dnyandev B.; Shin, Young Sup; Jang, Min Hwan; Kim, Gyudong; Lee, Hyuk Woo; Jeong, Lak Shin; Snijder, Eric J.; van Hemert, Martijn J.
Opublikowane w: Antimicrobial Agents and Chemotherapy, Numer 2, 2020, ISSN 0066-4804
Wydawca: American Society for Microbiology
DOI: 10.1128/aac.02532-19

Screening of a Library of FDA-Approved Drugs Identifies Several Enterovirus Replication Inhibitors That Target Viral Protein 2C

Autorzy: Rachel Ulferts, S. Matthijn de Boer, Lonneke van der Linden, Lisa Bauer, Hey Rhyoung Lyoo, Maria J. Maté, Julie Lichière, Bruno Canard, Daphne Lelieveld, Wienand Omta, David Egan, Bruno Coutard, Frank J. M. van Kuppeveld
Opublikowane w: Antimicrobial Agents and Chemotherapy, Numer 60/5, 2016, Strona(/y) 2627-2638, ISSN 0066-4804
Wydawca: American Society for Microbiology
DOI: 10.1128/AAC.02182-15

Mutations in Encephalomyocarditis Virus 3A Protein Uncouple the Dependency of Genome Replication on Host Factors Phosphatidylinositol 4-Kinase IIIα and Oxysterol-Binding Protein

Autorzy: Cristina M. Dorobantu, Lucian Albulescu, Heyrhyoung Lyoo, Mirjam van Kampen, Raffaele De Francesco, Volker Lohmann, Christian Harak, Hilde M. van der Schaar, Jeroen R. P. M. Strating, Alexander E. Gorbalenya, Frank J. M. van Kuppeveld
Opublikowane w: mSphere, Numer 1/3, 2016, Strona(/y) e00068-16, ISSN 2379-5042
Wydawca: American Society for Microbiology Journals
DOI: 10.1128/mSphere.00068-16

Replication of the Zika virus in different iPSC-derived neuronal cells and implications to assess efficacy of antivirals

Autorzy: Kristina Lanko, Kristel Eggermont, Abdulsamie Patel, Suzanne Kaptein, Leen Delang, Catherine M. Verfaillie, Johan Neyts
Opublikowane w: Antiviral Research, Numer 145, 2017, Strona(/y) 82-86, ISSN 0166-3542
Wydawca: Elsevier BV
DOI: 10.1016/j.antiviral.2017.07.010

Escaping Host Factor PI4KB Inhibition: Enterovirus Genomic RNA Replication in the Absence of Replication Organelles

Autorzy: Charlotte E. Melia, Hilde M. van der Schaar, Heyrhyoung Lyoo, Ronald W.A.L. Limpens, Qian Feng, Maryam Wahedi, Gijs J. Overheul, Ronald P. van Rij, Eric J. Snijder, Abraham J. Koster, Montserrat Bárcena, Frank J.M. van Kuppeveld
Opublikowane w: Cell Reports, Numer 21/3, 2017, Strona(/y) 587-599, ISSN 2211-1247
Wydawca: Cell Press
DOI: 10.1016/j.celrep.2017.09.068

Modulation of proteolytic polyprotein processing by coxsackievirus mutants resistant to inhibitors targeting phosphatidylinositol-4-kinase IIIβ or oxysterol binding protein

Autorzy: Heyrhyoung Lyoo, Cristina M. Dorobantu, Hilde M. van der Schaar, Frank J.M. van Kuppeveld
Opublikowane w: Antiviral Research, Numer 147, 2017, Strona(/y) 86-90, ISSN 0166-3542
Wydawca: Elsevier BV
DOI: 10.1016/j.antiviral.2017.10.006

Direct-acting antivirals and host-targeting strategies to combat enterovirus infections

Autorzy: Lisa Bauer, Heyrhyoung Lyoo, Hilde M van der Schaar, Jeroen RPM Strating, Frank JM van Kuppeveld
Opublikowane w: Current Opinion in Virology, Numer 24, 2017, Strona(/y) 1-8, ISSN 1879-6257
Wydawca: Elsevier BV
DOI: 10.1016/j.coviro.2017.03.009

Suramin inhibits Zika virus replication by interfering with virus attachment and release of infectious particles

Autorzy: Irina C. Albulescu, Kristina Kovacikova, Ali Tas, Eric J. Snijder, Martijn J. van Hemert
Opublikowane w: Antiviral Research, Numer 143, 2017, Strona(/y) 230-236, ISSN 0166-3542
Wydawca: Elsevier BV
DOI: 10.1016/j.antiviral.2017.04.016

Bis(benzofuran–thiazolidinone)s and bis(benzofuran–thiazinanone)s as inhibiting agents for chikungunya virus

Autorzy: Jih Ru Hwu, Nitesh K. Gupta, Shwu-Chen Tsay, Wen-Chieh Huang, Irina C. Albulescu, Kristina Kovacikova, Martijn J. van Hemert
Opublikowane w: Antiviral Research, Numer 146, 2017, Strona(/y) 96-101, ISSN 0166-3542
Wydawca: Elsevier BV
DOI: 10.1016/j.antiviral.2017.08.008

Structural and molecular basis of mismatch correction and ribavirin excision from coronavirus RNA

Autorzy: François Ferron, Lorenzo Subissi, Ana Theresa Silveira De Morais, Nhung Thi Tuyet Le, Marion Sevajol, Laure Gluais, Etienne Decroly, Clemens Vonrhein, Gérard Bricogne, Bruno Canard, Isabelle Imbert
Opublikowane w: Proceedings of the National Academy of Sciences, Numer 115/2, 2018, Strona(/y) E162-E171, ISSN 0027-8424
Wydawca: National Academy of Sciences
DOI: 10.1073/pnas.1718806115

A Reverse Genetics System for Zika Virus Based on a Simple Molecular Cloning Strategy

Autorzy: Maximilian Münster, Anna Płaszczyca, Mirko Cortese, Christopher Neufeldt, Sarah Goellner, Gang Long, Ralf Bartenschlager
Opublikowane w: Viruses, Numer 10/7, 2018, Strona(/y) 368, ISSN 1999-4915
Wydawca: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/v10070368

Structure-activity relationship study of itraconazole, a broad-range inhibitor of picornavirus replication that targets oxysterol-binding protein (OSBP)

Autorzy: Lisa Bauer, Salvatore Ferla, Sarah A. Head, Shridhar Bhat, Kalyan K. Pasunooti, Wei Q. Shi, Lucian Albulescu, Jun O. Liu, Andrea Brancale, Frank J.M. van Kuppeveld, Jeroen R.P.M. Strating
Opublikowane w: Antiviral Research, Numer 156, 2018, Strona(/y) 55-63, ISSN 0166-3542
Wydawca: Elsevier BV
DOI: 10.1016/j.antiviral.2018.05.010

Novel non-heteroarylpyrimidine (HAP) capsid assembly modifiers have a different mode of action from HAPs in vitro

Autorzy: Angelica Corcuera, Katharina Stolle, Stefan Hillmer, Stefan Seitz, Ji-Young Lee, Ralf Bartenschlager, Alexander Birkmann, Andreas Urban
Opublikowane w: Antiviral Research, Numer 158, 2018, Strona(/y) 135-142, ISSN 0166-3542
Wydawca: Elsevier BV
DOI: 10.1016/j.antiviral.2018.07.011

Antiviral effects of selected nucleoside analogs against human parechoviruses A1 and A3

Autorzy: Lanko, Kristina; Ma, Yipeng; Delang, Leen; Mirabelli, Carmen; Neyts, Johan
Opublikowane w: Lirias, Numer 1, 2018, ISSN 0166-3542
Wydawca: Elsevier BV
DOI: 10.1016/j.antiviral.2018.12.009

The Origin, Dynamic Morphology, and PI4P-Independent Formation of Encephalomyocarditis Virus Replication Organelles

Autorzy: C. E. Melia, H. M. van der Schaar, A. W. M. de Jong, H. R. Lyoo, E. J. Snijder, A. J. Koster, F. J. M. van Kuppeveld, M. Bárcena
Opublikowane w: mBio, Numer 9/2, 2018, Strona(/y) e00420-18, ISSN 2150-7511
Wydawca: American Society for Microbiology
DOI: 10.1128/mbio.00420-18

Discovery of Multitarget Agents Active as Broad-Spectrum Antivirals and Correctors of Cystic Fibrosis Transmembrane Conductance Regulator for Associated Pulmonary Diseases.

Autorzy: Tassini S, Sun L, Lanko K, Crespan E, Langron E, Falchi F, Kissova M, Armijos-Rivera JI, Delang L, Mirabelli C, Neyts J, Pieroni M, Cavalli A, Costantino G, Maga G, Vergani P, Leyssen P, Radi M
Opublikowane w: J Med Chem, Numer 60(4), 2017, Strona(/y) 1400-1416, ISSN 0022-2623
Wydawca: American Chemical Society
DOI: 10.1021/acs.jmedchem.6b01521

A novel interaction between dengue virus nonstructural protein 1 and the NS4A-2K-4B precursor is required for viral RNA replication but not for formation of the membranous replication organelle

Autorzy: Anna Płaszczyca, Pietro Scaturro, Christopher John Neufeldt, Mirko Cortese, Berati Cerikan, Salvatore Ferla, Andrea Brancale, Andreas Pichlmair, Ralf Bartenschlager
Opublikowane w: PLOS Pathogens, Numer 15/5, 2019, Strona(/y) e1007736, ISSN 1553-7374
Wydawca: PLOS
DOI: 10.1371/journal.ppat.1007736

An orthogonal proteomic survey uncovers novel Zika virus host factors

Autorzy: Pietro Scaturro, Alexey Stukalov, Darya A. Haas, Mirko Cortese, Kalina Draganova, Anna Płaszczyca, Ralf Bartenschlager, Magdalena Götz, Andreas Pichlmair
Opublikowane w: Nature, Numer 561/7722, 2018, Strona(/y) 253-257, ISSN 0028-0836
Wydawca: Nature Publishing Group
DOI: 10.1038/s41586-018-0484-5

ACBD3 Is an Essential Pan-enterovirus Host Factor That Mediates the Interaction between Viral 3A Protein and Cellular Protein PI4KB

Autorzy: Heyrhyoung Lyoo, Hilde M. van der Schaar, Cristina M. Dorobantu, Huib H. Rabouw, Jeroen R. P. M. Strating, Frank J. M. van Kuppeveld
Opublikowane w: mBio, Numer 10/1, 2019, ISSN 2150-7511
Wydawca: American Society for Microbiology
DOI: 10.1128/mBio.02742-18

Convergent evolution in the mechanisms of ACBD3 recruitment to picornavirus replication sites

Autorzy: Vladimira Horova, Heyrhyoung Lyoo, Bartosz Różycki, Dominika Chalupska, Miroslav Smola, Jana Humpolickova, Jeroen R. P. M. Strating, Frank J. M. van Kuppeveld, Evzen Boura, Martin Klima
Opublikowane w: PLOS Pathogens, Numer 15/8, 2019, Strona(/y) e1007962, ISSN 1553-7374
Wydawca: PLOS
DOI: 10.1371/journal.ppat.1007962

Fluoxetine Inhibits Enterovirus Replication by Targeting the Viral 2C Protein in a Stereospecific Manner

Autorzy: Lisa Bauer, Roberto Manganaro, Birgit Zonsics, Jeroen R. P. M. Strating, Priscila El Kazzi, Moira Lorenzo Lopez, Rachel Ulferts, Clara van Hoey, Maria J. Maté, Thierry Langer, Bruno Coutard, Andrea Brancale, Frank J. M. van Kuppeveld
Opublikowane w: ACS Infectious Diseases, Numer 5/9, 2019, Strona(/y) 1609-1623, ISSN 2373-8227
Wydawca: American Chemical Society
DOI: 10.1021/acsinfecdis.9b00179

Bypassing pan-enterovirus host factor PLA2G16

Autorzy: Jim Baggen, Yue Liu, Heyrhyoung Lyoo, Arno L. W. van Vliet, Maryam Wahedi, Jost W. de Bruin, Richard W. Roberts, Pieter Overduin, Adam Meijer, Michael G. Rossmann, Hendrik Jan Thibaut, Frank J. M. van Kuppeveld
Opublikowane w: Nature Communications, Numer 10/1, 2019, Strona(/y) 3171, ISSN 2041-1723
Wydawca: Nature Publishing Group
DOI: 10.1038/s41467-019-11256-z

Approved drugs screening against the nsP1 capping enzyme of Venezuelan equine encephalitis virus using an immuno-based assay

Autorzy: Ana S. Ferreira-Ramos, Changqing Li, Cécilia Eydoux, Jean Marie Contreras, Christophe Morice, Gilles Quérat, Alba Gigante, María-Jesús Pérez Pérez, Marie-Louise Jung, Bruno Canard, Jean-Claude Guillemot, Etienne Decroly, Bruno Coutard
Opublikowane w: Antiviral Research, Numer 163, 2019, Strona(/y) 59-69, ISSN 0166-3542
Wydawca: Elsevier BV
DOI: 10.1016/j.antiviral.2019.01.003

The Curious Case of the Nidovirus Exoribonuclease: Its Role in RNA Synthesis and Replication Fidelity

Autorzy: Natacha S. Ogando, Francois Ferron, Etienne Decroly, Bruno Canard, Clara C. Posthuma, Eric J. Snijder
Opublikowane w: Frontiers in Microbiology, Numer 10, 2019, ISSN 1664-302X
Wydawca: Frontiers Media
DOI: 10.3389/fmicb.2019.01813

Viral engagement with host receptors blocked by a novel class of tryptophan dendrimers that targets the 5-fold-axis of the enterovirus-A71 capsid

Autorzy: Liang Sun, Hyunwook Lee, Hendrik Jan Thibaut, Kristina Lanko, Eva Rivero-Buceta, Carol Bator, Belen Martinez-Gualda, Kai Dallmeier, Leen Delang, Pieter Leyssen, Federico Gago, Ana San-Félix, Susan Hafenstein, Carmen Mirabelli, Johan Neyts
Opublikowane w: PLOS Pathogens, Numer 15/5, 2019, Strona(/y) e1007760, ISSN 1553-7374
Wydawca: PLOS
DOI: 10.1371/journal.ppat.1007760

Characterization of the Golgi c10orf76-PI4KB complex, and its necessity for Golgi PI4P levels and enterovirus replication

Autorzy: J.A. McPhail, H.R. Lyoo, J.G. Pemberton, R.M. Hoffmann, W. van Elst, J.R.P.M. Strating, M.L. Jenkins, J.T.B. Stariha, C.J. Powell, M.J. Boulanger, T. Balla, F.J.M. van Kuppeveld, J.E. Burke
Opublikowane w: EMBO Reports, Numer 21:e48441, 2020, ISSN 1469-221X
Wydawca: Nature Publishing Group
DOI: 10.15252/embr.201948441

No evidence for viral small RNA production and antiviral function of Argonaute 2 in human cells

Autorzy: Susan Schuster, Gijs J. Overheul, Lisa Bauer, Frank J. M. van Kuppeveld, Ronald P. van Rij
Opublikowane w: Scientific Reports, Numer 9/1, 2019, ISSN 2045-2322
Wydawca: Nature Publishing Group
DOI: 10.1038/s41598-019-50287-w

Viral rewiring of cellular lipid metabolism to create membranous replication compartments

Autorzy: Jeroen RPM Strating, Frank JM van Kuppeveld
Opublikowane w: Current Opinion in Cell Biology, Numer 47, 2017, Strona(/y) 24-33, ISSN 0955-0674
Wydawca: Elsevier BV
DOI: 10.1016/j.ceb.2017.02.005

The Enzymatic Activity of the nsp14 Exoribonuclease Is Critical for Replication of MERS-CoV and SARS-CoV-2

Autorzy: Ogando NS, Zevenhoven-Dobbe JC, van der Meer Y, Bredenbeek PJ, Posthuma CC, Snijder EJ
Opublikowane w: Journal of Virology, Numer Journal of Virology 94/23, 2020, ISSN 1098-5514
Wydawca: American Society for Microbiology
DOI: 10.1128/jvi.01246-20

Novel Class of Chikungunya Virus Small Molecule Inhibitors That Targets the Viral Capping Machinery

Autorzy: Rana Abdelnabi, Kristina Kovacikova, Julia Moesslacher, Kim Donckers, Verena Battisti, Pieter Leyssen, Thierry Langer, , Gerhard Puerstinger, Gilles Quérat, Changqing Li, Etienne Decroly, Ali Tas, Arnaud Marchand, Patrick Chaltin, Bruno Coutard, Martijn van Hemert, Johan Neyts, Leen Delang
Opublikowane w: Antimicrobial Agents and Chemotherapy, Numer 64/7, 2020, ISSN 0066-4804
Wydawca: American Society for Microbiology
DOI: 10.1128/aac.00649-20

Structural Insights into the Mechanisms of Action of Functionally Distinct Classes of Chikungunya Virus Nonstructural Protein 1 Inhibitors

Autorzy: Kristina Kovacikova; Marina Gorostiola González; Rhian Jones; Juan Reguera; Alba Gigante; María-Jesús Pérez-Pérez; Gerhard Pürstinger; Julia Moesslacher; Thierry Langer; Lak Shin Jeong; Leen Delang; Johan Neyts; Eric J. Snijder; Gerard J. P. van Westen; Martijn J. van Hemert
Opublikowane w: Antimicrobial Agents and Chemotherapy, Numer 4, 2021, ISSN 0066-4804
Wydawca: American Society for Microbiology
DOI: 10.1128/aac.02566-20

Synthesis and antiviral effect of novel fluoxetine analogues as enterovirus 2C inhibitors

Autorzy: Roberto Manganaro; Birgit Zonsics; Lisa Bauer; Moira Lorenzo Lopez; Tim Donselaar; Marleen Zwaagstra; Fabiana Saporito; Salvatore Ferla; Jeroen R.P.M. Strating; Bruno Coutard; Daniel L. Hurdiss; Frank J. M. van Kuppeveld; Andrea Brancale
Opublikowane w: Antiviral Research, Numer 6, 2020, ISSN 0166-3542
Wydawca: Elsevier BV
DOI: 10.1016/j.antiviral.2020.104781

Snapshots of ADP-ribose bound to Getah virus macro domain reveal an intriguing choreography

Autorzy: Ana Sofia Ferreira Ramos; Gerlind Sulzenbacher; Bruno Canard; Bruno Coutard
Opublikowane w: Scientific Reports, Numer 4, 2020, ISSN 2045-2322
Wydawca: Nature Publishing Group
DOI: 10.1038/s41598-020-70870-w

Design, Synthesis, and Anti-RNA Virus Activity of 6′-Fluorinated-Aristeromycin Analogues

Autorzy: Ji-seong Yoon, Gyudong Kim, Dnyandev B. Jarhad, Hong-Rae Kim, Young-Sup Shin, Shuhao Qu, Pramod K. Sahu, Hea Ok Kim, Hyuk Woo Lee, Su Bin Wang, Yun Jeong Kong, Tong-Shin Chang, Natacha S. Ogando, Kristina Kovacikova, Eric J. Snijder, Clara C. Posthuma, Martijn J. van Hemert, and Lak Shin Jeong
Opublikowane w: Journal of Medicinal Chemistry, Numer 62/13, 2019, ISSN 0022-2623
Wydawca: American Chemical Society
DOI: 10.1021/acs.jmedchem.9b00781

The quest for broad-spectrum coronavirus inhibitors 2021

Autorzy: Lima Leite Ogando, N.S.
Opublikowane w: 2021
Wydawca: Leiden University

From repurposed drugs to pan enterovirus and rhinovirus inhibitors

Autorzy: Bauer, Lisa
Opublikowane w: 2021
Wydawca: Utrecht University

Role of host factors regulating membrane homeostasis in enterovirus replication

Autorzy: Erion Lyoo
Opublikowane w: 2021
Wydawca: Utrecht University

Chikungunya virus nonstructural protein 1 as an antiviral target

Autorzy: Kovacikova, K
Opublikowane w: 2021
Wydawca: Leiden University

Meeting report: 31st International Conference on Antiviral Research

Autorzy: Mike Bray, Graciela Andrei, Ester Ballana, Kara Carter, David Durantel, Brian Gentry, Zlatko Janeba, Jennifer Moffat, Clasien J. Oomen, Bart Tarbet, Eva Riveira-Muñoz, José. A. Esté
Opublikowane w: Antiviral Research, Numer 158, 2018, Strona(/y) 88-102, ISSN 0166-3542
Wydawca: Elsevier BV
DOI: 10.1016/j.antiviral.2018.08.002

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