Blocking NS3-NS4B interaction inhibits dengue virus in non-human primates.


Journal

Nature
ISSN: 1476-4687
Titre abrégé: Nature
Pays: England
ID NLM: 0410462

Informations de publication

Date de publication:
03 2023
Historique:
received: 29 06 2022
accepted: 03 02 2023
pubmed: 17 3 2023
medline: 25 3 2023
entrez: 16 3 2023
Statut: ppublish

Résumé

Dengue is a major health threat and the number of symptomatic infections caused by the four dengue serotypes is estimated to be 96 million

Identifiants

pubmed: 36922586
doi: 10.1038/s41586-023-05790-6
pii: 10.1038/s41586-023-05790-6
pmc: PMC10033419
doi:

Substances chimiques

Antiviral Agents 0
Viral Nonstructural Proteins 0
NS3 protein, flavivirus 0
NS4B protein, Dengue virus 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

678-686

Subventions

Organisme : NIAID NIH HHS
ID : HHSN272201700040I
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2023. The Author(s).

Références

Bhatt, S. et al. The global distribution and burden of dengue. Nature 496, 504–507 (2013).
pubmed: 23563266 pmcid: 3651993 doi: 10.1038/nature12060
Stanaway, J. D. et al. The global burden of dengue: an analysis from the global burden of disease study 2013. Lancet Infect. Dis. 16, 712–723 (2016).
pubmed: 26874619 pmcid: 5012511 doi: 10.1016/S1473-3099(16)00026-8
Kaptein, S. J. F. et al. A pan-serotype dengue virus inhibitor targeting the NS3–NS4B interaction. Nature 598, 504–509 (2021).
pubmed: 34616043 doi: 10.1038/s41586-021-03990-6
Ackaert, O. et al. Safety, tolerability and pharmacokinetics of a novel pan-serotype dengue antiviral small molecule in a phase 1, double-blind, randomized, dose-escalation study [abstract 0582]. in The American Society of Tropical Medicine & Hygiene (ASTMH) Virtual Meeting Abstract Book (2021).
Zeng, W., Halasa-Rappel, Y. A., Durand, L., Coudeville, L. & Shepard, D. S. Impact of a nonfatal dengue episode on disability-adjusted life years: a systematic analysis. Am. J. Trop. Med. Hyg. 99, 1458–1465 (2018).
pubmed: 30277202 pmcid: 6283510 doi: 10.4269/ajtmh.18-0309
Global Strategy for Dengue Prevention and Control, 2012–2020 (WHO, 2012); http://apps.who.int/iris/bitstream/10665/75303/1/9789241504034_eng.pdf?ua=1
Ebi, K. L. & Nealon, J. Dengue in a changing climate. Environ. Res. 151, 115–123 (2016).
pubmed: 27475051 doi: 10.1016/j.envres.2016.07.026
Gubler, D. J. Dengue, urbanization and globalization: the unholy trinity of the 21
pubmed: 22500131 pmcid: 3317603 doi: 10.2149/tmh.2011-S05
Messina, J. P. et al. The current and future global distribution and population at risk of dengue. Nat. Microbiol. 4, 1508–1515 (2019).
pubmed: 31182801 pmcid: 6784886 doi: 10.1038/s41564-019-0476-8
Ong, A., Sandar, M., Chen, M. I. & Sin, L. Y. Fatal dengue hemorrhagic fever in adults during a dengue epidemic in Singapore. Int. J. Infect. Dis. 11, 263–267 (2007).
pubmed: 16899384 doi: 10.1016/j.ijid.2006.02.012
Halstead, S. B. Dengue. Lancet 370, 1644–1652 (2007).
pubmed: 17993365 doi: 10.1016/S0140-6736(07)61687-0
Katzelnick, L. C. et al. Antibody-dependent enhancement of severe dengue disease in humans. Science 358, 929–932 (2017).
pubmed: 29097492 pmcid: 5858873 doi: 10.1126/science.aan6836
Thomas, S. J. & Yoon, I.-K. A review of Dengvaxia®: development to deployment. Hum. Vaccin. Immunother. 15, 2295–2314 (2019).
pubmed: 31589551 pmcid: 6816420 doi: 10.1080/21645515.2019.1658503
Wilder-Smith, A. The first licensed dengue vaccine: can it be used in travelers? Curr. Opin. Infect. Dis. 32, 394–400 (2019).
pubmed: 31305495 doi: 10.1097/QCO.0000000000000573
Fongwen, N. et al. Target product profile for a dengue pre-vaccination screening test. PLoS Negl. Trop. Dis. 15, e0009557 (2021).
pubmed: 34324505 pmcid: 8320982 doi: 10.1371/journal.pntd.0009557
[No authors listed.] Dengue vaccine: WHO position paper, September 2018—recommendations. Vaccine 37, 4848–4849 (2019).
Takeda’s QDENGA®▼ (Dengue Tetravalent Vaccine [Live, Attenuated]) Approved in Indonesia for Use Regardless of Prior Dengue Exposure (Takeda, 2022); https://www.takeda.com/newsroom/newsreleases/2022/takedas-qdenga-dengue-tetravalent-vaccine-live-attenuated-approved-in-indonesia-for-use-regardless-of-prior-dengue-exposure/ .
Takeda’s QDENGA®▼ (Dengue Tetravalent Vaccine [Live, Attenuated]) Approved for Use in European Union (Takeda, 2022); https://www.takeda.com/newsroom/newsreleases/2022/takedas-qdenga-dengue-tetravalent-vaccine-live-attenuated-approved-for-use-in-european-union/ .
Takeda UK Ltd. announces MHRA approval for dengue virus vaccine candidate Qdenga®▼ (Bloomberg, 2023); https://www.bloomberg.com/press-releases/2023-02-06/takeda-uk-ltd-announces-mhra-approval-for-dengue-virus-vaccine-candidate-qdenga .
Low, J. G., Gatsinga, R., Vasudevan, S. G. & Sampath, A. Dengue antiviral development: a continuing journey. Adv. Exp. Med. Biol. 1062, 319–332 (2018).
pubmed: 29845542 doi: 10.1007/978-981-10-8727-1_22
Whitehorn, J. et al. Dengue therapeutics, chemoprophylaxis, and allied tools: state of the art and future directions. PLoS Negl. Trop. Dis. 8, e3025 (2014).
pubmed: 25166493 pmcid: 4148227 doi: 10.1371/journal.pntd.0003025
Kou, Z. et al. Monocytes, but not T or B cells, are the principal target cells for dengue virus (DV) infection among human peripheral blood mononuclear cells. J. Med. Virol. 80, 134–146 (2008).
pubmed: 18041019 doi: 10.1002/jmv.21051
Touret, F. et al. Phylogenetically based establishment of a dengue virus panel, representing all available genotypes, as a tool in dengue drug discovery. Antiviral Res. 168, 109–113 (2019).
pubmed: 31085207 doi: 10.1016/j.antiviral.2019.05.005
Williams, K. L., Zompi, S., Beatty, P. R. & Harris, E. A mouse model for studying dengue virus pathogenesis and immune response. Ann. N. Y. Acad. Sci. 1171, E12–E23 (2009).
pubmed: 19751398 doi: 10.1111/j.1749-6632.2009.05057.x
Hsu, A. et al. Pharmacokinetic-pharmacodynamic analysis of lopinavir-ritonavir in combination with efavirenz and two nucleoside reverse transcriptase inhibitors in extensively pretreated human immunodeficiency virus-infected patients. Antimicrob. Agents Chemother. 47, 350–359 (2003).
pubmed: 12499212 pmcid: 148953 doi: 10.1128/AAC.47.1.350-359.2003
Gatti, G. et al. Pharmacokinetics and pharmacodynamics of nelfinavir administered twice or thrice daily to human immunodeficiency virus type 1-infected children. Clin. Infect. Dis. 36, 1476–1482 (2003).
pubmed: 12766843 doi: 10.1086/375062
Mo, H. et al. Estimation of inhibitory quotient using a comparative equilibrium dialysis assay for prediction of viral response to hepatitis C virus inhibitors. J. Viral Hepat. 18, 338–348 (2011).
pubmed: 20456634 doi: 10.1111/j.1365-2893.2010.01314.x
Herrmann, E. et al. Viral kinetics in patients with chronic hepatitis C treated with the serine protease inhibitor Biln 2061. Antivir. Ther. 11, 371–376 (2005).
doi: 10.1177/135965350601100303
Norshidah, H., Vignesh, R. & Lai, N. S. Updates on dengue vaccine and antiviral: where are we heading? Molecules 26, 6768 (2021).
pubmed: 34833860 pmcid: 8620506 doi: 10.3390/molecules26226768
Guzman, M. G. & Harris, E. Dengue. Lancet 385, 453–465 (2015).
pubmed: 25230594 doi: 10.1016/S0140-6736(14)60572-9
Wang, Q.-Y. et al. Discovery of dengue virus NS4B inhibitors. J. Virol. 89, 8233–8244 (2015).
pubmed: 26018165 pmcid: 4524232 doi: 10.1128/JVI.00855-15
Xie, X., Zou, J., Wang, Q. Y. & Shi, P. Y. Targeting dengue virus NS4B protein for drug discovery. Antiviral Res. 118, 39–45 (2015).
pubmed: 25796970 doi: 10.1016/j.antiviral.2015.03.007
Hernandez-Morales, I. et al. Characterization of a dengue NS4B inhibitor originating from an HCV small molecule library. Antiviral Res. 147, 149–158 (2017).
pubmed: 29037976 doi: 10.1016/j.antiviral.2017.10.011
Wilder-Smith, A. Dengue vaccine development: status and future. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 63, 40–44 (2020).
pubmed: 31784763 doi: 10.1007/s00103-019-03060-3
Agudelo Higuita, N. I., White, B. P., Franco-Paredes, C. & McGhee, M. A. An update on prevention of malaria in travelers. Ther. Adv. Infect. Dis. 8, 20499361211040690 (2021).
pubmed: 34484736 pmcid: 8408895
Nakato, H., Vivancos, R. & Hunter, P. R. A systematic review and meta-analysis of the effectiveness and safety of atovaquone proguanil (Malarone) for chemoprophylaxis against malaria. J. Antimicrob. Chemother. 60, 929–936 (2007).
pubmed: 17848375 doi: 10.1093/jac/dkm337
Straubinger, T., Kay, K. & Bies, R. Modeling HIV pre-exposure prophylaxis. Front. Pharmacol. 10, 1514 (2019).
pubmed: 32082142 doi: 10.3389/fphar.2019.01514
Orr, H. A. & Unckless, R. L. The population genetics of evolutionary rescue. PLoS Genet. 10, e1004551 (2014).
pubmed: 25121960 pmcid: 4133041 doi: 10.1371/journal.pgen.1004551
Nguyen, N. M. et al. A randomized, double-blind placebo controlled trial of balapiravir, a polymerase inhibitor, in adult dengue patients. J. Infect. Dis. 207, 1442–1450 (2013).
pubmed: 22807519 doi: 10.1093/infdis/jis470
Waickman, A. T. et al. Evolution of inflammation and immunity in a dengue virus 1 human infection model. Sci. Transl. Med. 14, eabo5019 (2022).
Raafat, N., Blacksell, S. D. & Maude, R. J. A review of dengue diagnostics and implications for surveillance and control. Trans. R. Soc. Trop. Med. Hyg. 113, 653–660 (2019).
pubmed: 31365115 pmcid: 6836713 doi: 10.1093/trstmh/trz068
Vaughn, D. W. et al. Dengue viremia titer, antibody response pattern, and virus serotype correlate with disease severity. J. Infect. Dis. 181, 2–9 (2000).
pubmed: 10608744 doi: 10.1086/315215
Libraty, D. H. et al. High circulating levels of the dengue virus nonstructural protein NS1 early in dengue illness correlate with the development of dengue hemorrhagic fever. J. Infect. Dis. 186, 1165–1168 (2002).
pubmed: 12355369 doi: 10.1086/343813
Murgue, B., Roche, C., Chungue, E. & Deparis, X. Prospective study of the duration and magnitude of viraemia in children hospitalised during the 1996-1997 dengue-2 outbreak in French Polynesia. J. Med. Virol. 60, 432–438 (2000).
pubmed: 10686027 doi: 10.1002/(SICI)1096-9071(200004)60:4<432::AID-JMV11>3.0.CO;2-7
Busch, M. P. et al. Duration of dengue viremia in blood donors and relationships between donor viremia, infection incidence and clinical case reports during a large epidemic. J. Infect. Dis. 214, 49–54 (2016).
pubmed: 27302934 pmcid: 4907419 doi: 10.1093/infdis/jiw122
Le Pogam, S. et al. Selection and characterization of replicon variants dually resistant to thumb- and palm-binding nonnucleoside polymerase inhibitors of the hepatitis C virus. J. Virol. 80, 6146–6154 (2006).
pubmed: 16731953 pmcid: 1472602 doi: 10.1128/JVI.02628-05
Thompson, A. J., Locarnini, S. A. & Beard, M. R. Resistance to anti-HCV protease inhibitors. Curr. Opin. Virol. 1, 599–606 (2011).
pubmed: 22440917 doi: 10.1016/j.coviro.2011.10.001
Liu, T., Sun, Q., Gu, J., Cen, S. & Zhang, Q. Characterization of the tenofovir resistance-associated mutations in the hepatitis B virus isolates across genotypes A to D. Antiviral Res. 203, 105348 (2022).
pubmed: 35644506 doi: 10.1016/j.antiviral.2022.105348
Kayesh, M. E. H. & Tsukiyama-Kohara, K. Mammalian animal models for dengue virus infection: a recent overview. Arch. Virol. 167, 31–44 (2022).
pubmed: 34761286 doi: 10.1007/s00705-021-05298-2
Miller, S., Sparacio, S. & Bartenschlager, R. Subcellular localization and membrane topology of the dengue virus type 2 non-structural protein 4B. J. Biol. Chem. 281, 8854–8863 (2006).
pubmed: 16436383 doi: 10.1074/jbc.M512697200
Zmurko, J., Neyts, J. & Dallmeier, K. Flaviviral NS4b, chameleon and jack-in-the-box roles in viral replication and pathogenesis, and a molecular target for antiviral intervention. Rev. Med. Virol. 25, 205–223 (2015).
pubmed: 25828437 pmcid: 4864441 doi: 10.1002/rmv.1835
Chatel-Chaix, L. et al. A combined genetic-proteomic approach identifies residues within dengue virus NS4B critical for interaction with NS3 and viral replication. J. Virol. 89, 7170–7186 (2015).
pubmed: 25926641 pmcid: 4473547 doi: 10.1128/JVI.00867-15
Fischl, W. & Bartenschlager, R. High-throughput screening using dengue virus reporter genomes. Methods Mol. Biol. 1030, 205–219 (2013).
pubmed: 23821271 doi: 10.1007/978-1-62703-484-5_17
Endy, T. P. et al. A phase 1, open-label assessment of a dengue virus-1 live virus human challenge strain. J. Infect. Dis. 223, 258–267 (2021).
pubmed: 32572470 doi: 10.1093/infdis/jiaa351
Milligan, G. N. et al. Spectrum of activity testing for therapeutics against all four dengue virus serotypes in AG129 mouse models: proof-of-concept studies with the adenosine nucleoside inhibitor NITD-008. Antiviral Res. 154, 104–109 (2018).
pubmed: 29665374 pmcid: 6685202 doi: 10.1016/j.antiviral.2018.04.012
Gong, E. Y. et al. Cell-based antiviral assays for screening and profiling inhibitors against dengue virus. Methods Mol. Biol. 1030, 185–194 (2013).
pubmed: 23821269 doi: 10.1007/978-1-62703-484-5_15
Kaptein, S. J. et al. A derivate of the antibiotic doxorubicin is a selective inhibitor of dengue and yellow fever virus replication in vitro. Antimicrob. Agents Chemother. 54, 5269–5280 (2010).
pubmed: 20837762 pmcid: 2981273 doi: 10.1128/AAC.00686-10
De Burghgraeve, T. et al. An analogue of the antibiotic teicoplanin prevents flavivirus entry in vitro. PLoS ONE 7, e37244 (2012).
pubmed: 22624001 pmcid: 3356272 doi: 10.1371/journal.pone.0037244
Santiago, G. A. et al. Analytical and clinical performance of the CDC real time RT-PCR assay for detection and typing of dengue virus. PLoS Negl. Trop. Dis. 7, e2311 (2013).
pubmed: 23875046 pmcid: 3708876 doi: 10.1371/journal.pntd.0002311
Kato, F. et al. Natural infection of cynomolgus monkeys with dengue virus occurs in epidemic cycles in the Philippines. J. Gen. Virol. 94, 2202–2207 (2013).
pubmed: 23851439 doi: 10.1099/vir.0.055343-0
Kärber, G. Beitrag zur kollektiven Behandlung pharmakologischer Reihenversuche. Naunyn Schmiedebergs Arch. Exp. Pathol. Pharmakol. 162, 480–483 (1931).
doi: 10.1007/BF01863914
Spearman, C. The method of “right and wrong cases” (constant stimuli) without Gauss’s formula. Br. J. Psychol. 2, 227–242 (1908).
Sadon, N. et al. A new quantitative RT-PCR method for sensitive detection of dengue virus in serum samples. J. Virol. Methods 153, 1–6 (2008).
pubmed: 18652847 doi: 10.1016/j.jviromet.2008.06.023
Klungthong, C. et al. Monitoring and improving the sensitivity of dengue nested RT-PCR used in longitudinal surveillance in Thailand. J. Clin. Virol. 63, 25–31 (2015).
pubmed: 25600599 doi: 10.1016/j.jcv.2014.12.009
Jaki, T. & Wolfsegger, M. J. Estimation of pharmacokinetic parameters with the R package PK. Pharm. Stat. 10, 284–288 (2011).
doi: 10.1002/pst.449
Verbist, B. M. et al. VirVarSeq: a low-frequency virus variant detection pipeline for Illumina sequencing using adaptive base-calling accuracy filtering. Bioinformatics 31, 94–101 (2015).
pubmed: 25178459 doi: 10.1093/bioinformatics/btu587

Auteurs

Olivia Goethals (O)

Janssen Global Public Health, Janssen Pharmaceutica NV, Beerse, Belgium.

Suzanne J F Kaptein (SJF)

Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, KU Leuven, Leuven, Belgium.

Bart Kesteleyn (B)

Janssen Research & Development, Janssen Pharmaceutica NV, Beerse, Belgium.

Jean-François Bonfanti (JF)

Janssen Infectious Diseases Discovery, Janssen-Cilag, Val de Reuil, France.
Galapagos, Romainville, France.

Liesbeth Van Wesenbeeck (L)

Janssen Research & Development, Janssen Pharmaceutica NV, Beerse, Belgium.

Dorothée Bardiot (D)

Cistim Leuven vzw, Leuven, Belgium.

Ernst J Verschoor (EJ)

Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.

Babs E Verstrepen (BE)

Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.

Zahra Fagrouch (Z)

Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.

J Robert Putnak (JR)

Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Dominik Kiemel (D)

Heidelberg University, Medical Faculty Heidelberg, Department of Infectious Diseases, Molecular Virology, Center for Integrative Infectious Diseases Research, Heidelberg, Germany.

Oliver Ackaert (O)

Janssen Clinical Pharmacology and Pharmacometrics, Janssen Pharmaceutica NV, Beerse, Belgium.

Roel Straetemans (R)

Statistics and Decision Sciences, Janssen Pharmaceutica NV, Beerse, Belgium.

Sophie Lachau-Durand (S)

Janssen Research & Development, Janssen Pharmaceutica NV, Beerse, Belgium.

Peggy Geluykens (P)

Janssen Research & Development, Janssen Pharmaceutica NV, Beerse, Belgium.
Discovery, Charles River Beerse, Beerse, Belgium.

Marjolein Crabbe (M)

Statistics and Decision Sciences, Janssen Pharmaceutica NV, Beerse, Belgium.

Kim Thys (K)

Janssen Research & Development, Janssen Pharmaceutica NV, Beerse, Belgium.

Bart Stoops (B)

Janssen Research & Development, Janssen Pharmaceutica NV, Beerse, Belgium.

Oliver Lenz (O)

Janssen Research & Development, Janssen Pharmaceutica NV, Beerse, Belgium.

Lotke Tambuyzer (L)

Janssen Research & Development, Janssen Pharmaceutica NV, Beerse, Belgium.

Sandra De Meyer (S)

Janssen Research & Development, Janssen Pharmaceutica NV, Beerse, Belgium.

Kai Dallmeier (K)

Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, KU Leuven, Leuven, Belgium.

Michael K McCracken (MK)

Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Gregory D Gromowski (GD)

Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Wiriya Rutvisuttinunt (W)

Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Richard G Jarman (RG)

Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Nicos Karasavvas (N)

Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Franck Touret (F)

Unité des Virus Émergents, Aix-Marseille Université-IRD 190-Inserm 1207, Marseille, France.

Gilles Querat (G)

Unité des Virus Émergents, Aix-Marseille Université-IRD 190-Inserm 1207, Marseille, France.

Xavier de Lamballerie (X)

Unité des Virus Émergents, Aix-Marseille Université-IRD 190-Inserm 1207, Marseille, France.

Laurent Chatel-Chaix (L)

Heidelberg University, Medical Faculty Heidelberg, Department of Infectious Diseases, Molecular Virology, Center for Integrative Infectious Diseases Research, Heidelberg, Germany.
Centre Armand-Frappier Santé Biotechnologie, Institut National de la Recherche Scientifique, Laval, Quebec, Canada.

Gregg N Milligan (GN)

Sealy Institute for Vaccine Sciences, The University of Texas Medical Branch Health, Galveston, TX, USA.

David W C Beasley (DWC)

Sealy Institute for Vaccine Sciences, The University of Texas Medical Branch Health, Galveston, TX, USA.

Nigel Bourne (N)

Sealy Institute for Vaccine Sciences, The University of Texas Medical Branch Health, Galveston, TX, USA.

Alan D T Barrett (ADT)

Sealy Institute for Vaccine Sciences, The University of Texas Medical Branch Health, Galveston, TX, USA.

Arnaud Marchand (A)

Cistim Leuven vzw, Leuven, Belgium.

Tim H M Jonckers (THM)

Janssen Research & Development, Janssen Pharmaceutica NV, Beerse, Belgium.

Pierre Raboisson (P)

Janssen Research & Development, Janssen Pharmaceutica NV, Beerse, Belgium.
Galapagos NV, Mechelen, Belgium.

Kenny Simmen (K)

Johnson & Johnson Innovation, London, UK.

Patrick Chaltin (P)

Cistim Leuven vzw, Leuven, Belgium.
Centre for Drug Design and Discovery (CD3), KU Leuven, Leuven, Belgium.

Ralf Bartenschlager (R)

Heidelberg University, Medical Faculty Heidelberg, Department of Infectious Diseases, Molecular Virology, Center for Integrative Infectious Diseases Research, Heidelberg, Germany.
German Centre for Infection Research, Heidelberg Partner Site, Heidelberg, Germany.

Willy M Bogers (WM)

Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.

Johan Neyts (J)

Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, KU Leuven, Leuven, Belgium.
Global Virus Network (GVN), Baltimore, MD, USA.

Marnix Van Loock (M)

Janssen Global Public Health, Janssen Pharmaceutica NV, Beerse, Belgium. mvloock@its.jnj.com.

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