Novel dengue virus NS2B/NS3 protease inhibitors

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dc.contributor.authorWu, Hongmei
dc.contributor.authorBock, Stefanie
dc.contributor.authorSnitko, Mariya
dc.contributor.authorBerger, Thilo
dc.contributor.authorWeidner, Thomas
dc.contributor.authorHolloway, Steven
dc.contributor.authorKanitz, Manuel
dc.contributor.authorDiederich, Wibke E.
dc.contributor.authorSteuber, Holger
dc.contributor.authorWalter, Christof
dc.contributor.authorHofmann, Daniela
dc.contributor.authorWeißbrich, Benedikt
dc.contributor.authorSpannaus, Ralf
dc.contributor.authorAcosta, Eliana G.
dc.contributor.authorBartenschlager, Ralf
dc.contributor.authorEngels, Bernd
dc.contributor.authorSchirmeister, Tanja
dc.contributor.authorBodem, Jochen
dc.date.accessioned2022-12-07T11:15:48Z
dc.date.available2022-12-07T11:15:48Z
dc.date.issued2015
dc.description.abstractDengue fever is a severe, widespread, and neglected disease with more than 2 million diagnosed infections per year. The dengue virus NS2B/NS3 protease (PR) represents a prime target for rational drug design. At the moment, there are no clinical PR inhibitors (PIs) available. We have identified diaryl (thio)ethers as candidates for a novel class of PIs. Here, we report the selective and noncompetitive inhibition of the serotype 2 and 3 dengue virus PR in vitro and in cells by benzothiazole derivatives exhibiting 50% inhibitory concentrations (IC50s) in the low-micromolar range. Inhibition of replication of DENV serotypes 1 to 3 was specific, since all substances influenced neither hepatitis C virus (HCV) nor HIV-1 replication. Molecular docking suggests binding at a specific allosteric binding site. In addition to the in vitro assays, a cell-based PR assay was developed to test these substances in a replication-independent way. The new compounds inhibited the DENV PR with IC50s in the low-micromolar or submicromolar range in cells. Furthermore, these novel PIs inhibit viral replication at submicromolar concentrations.en_GB
dc.description.sponsorshipDFG, Open Access-Publizieren Universität Mainz / Universitätsmedizinde
dc.identifier.doihttp://doi.org/10.25358/openscience-8490
dc.identifier.urihttps://openscience.ub.uni-mainz.de/handle/20.500.12030/8506
dc.language.isoengde
dc.rightsInC-1.0*
dc.rights.urihttps://rightsstatements.org/vocab/InC/1.0/*
dc.subject.ddc570 Biowissenschaftende_DE
dc.subject.ddc570 Life sciencesen_GB
dc.titleNovel dengue virus NS2B/NS3 protease inhibitorsen_GB
dc.typeZeitschriftenaufsatzde
jgu.identifier.pmid25487800
jgu.journal.issue2de
jgu.journal.titleAntimicrobial agents and chemotherapyde
jgu.journal.volume59de
jgu.organisation.departmentFB 09 Chemie, Pharmazie u. Geowissensch.de
jgu.organisation.nameJohannes Gutenberg-Universität Mainz
jgu.organisation.number7950
jgu.organisation.placeMainz
jgu.organisation.rorhttps://ror.org/023b0x485
jgu.pages.end1109de
jgu.pages.start1100de
jgu.publisher.doi10.1128/AAC.03543-14de
jgu.publisher.issn1098-6596de
jgu.publisher.issn0066-4804de
jgu.publisher.nameSoc.de
jgu.publisher.placeWashington, DCde
jgu.publisher.urihttp://dx.doi.org/10.1128/AAC.03543-14de
jgu.publisher.year2015
jgu.rights.accessrightsopenAccess
jgu.subject.ddccode570de
jgu.type.dinitypeArticleen_GB
jgu.type.resourceTextde
jgu.type.versionPublished versionde
opus.affiliatedSchirmeister, Tanja
opus.date.modified2018-09-05T08:56:09Z
opus.identifier.opusid50559
opus.importsourcepubmed
opus.institute.number0908
opus.metadataonlyfalse
opus.organisation.stringFB 09: Chemie, Pharmazie und Geowissenschaften: Institut für Pharmaziede_DE
opus.subject.dfgcode00-000
opus.type.contenttypeKeinede_DE
opus.type.contenttypeNoneen_EN

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