Novel dengue virus NS2B/NS3 protease inhibitors

Publikationstyp:
Zeitschriftenaufsatz
Metadaten:
Autoren
  • Hongmei Wu
  • Stefanie Bock
  • Mariya Snitko
  • Thilo Berger
  • Thomas Weidner
  • Steven Holloway
  • Manuel Kanitz
  • Wibke E Diederich
  • Holger Steuber
  • Christof Walter
  • Daniela Hofmann
  • Benedikt Weißbrich
  • Ralf Spannaus
  • Eliana G Acosta
  • Ralf Bartenschlager
  • Bernd Engels
  • Tanja Schirmeister
  • Jochen Bodem
Sammlungen
  • metadata
ISSN
1098-6596
Ausgabe der Veröffentlichung
2
Zeitschrift
Antimicrobial agents and chemotherapy
Schlüsselwörter
  • 570 Biowissenschaften
  • 570 Life sciences
Sprache
eng
Paginierung
Seiten: 1100 - 1109
Datum der Veröffentlichung
2015
Herausgeber
Soc.
Herausgeber URL
http://dx.doi.org/10.1128/AAC.03543-14
Datum der Datenerfassung
2020
Datum, an dem der Datensatz öffentlich gemacht wurde
2020
Zugang
Public
Titel
Novel dengue virus NS2B/NS3 protease inhibitors
Ausgabe der Zeitschrift
59

Datenquelle: METADATA.UB

Andere Metadatenquellen:
Autoren
  • Hongmei Wu
  • Stefanie Bock
  • Mariya Snitko
  • Thilo Berger
  • Thomas Weidner
  • Steven Holloway
  • Manuel Kanitz
  • Wibke E Diederich
  • Holger Steuber
  • Christof Walter
  • Daniela Hofmann
  • Benedikt Weissbrich
  • Ralf Spannaus
  • Eliana G Acosta
  • Ralf Bartenschlager
  • Bernd Engels
  • Tanja Schirmeister
  • Jochen Bodem
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000348610000042&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1128/AAC.03543-14
eISSN
1098-6596
Externe Identifier
  • Clarivate Analytics Document Solution ID: CA0LT
  • PubMed Identifier: 25487800
ISSN
0066-4804
Ausgabe der Veröffentlichung
2
Zeitschrift
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Paginierung
1100 - 1109
Datum der Veröffentlichung
2015
Status
Published
Titel
Novel Dengue Virus NS2B/NS3 Protease Inhibitors
Sub types
  • Article
Ausgabe der Zeitschrift
59

Datenquelle: Web of Science (Lite)

Abstract
<jats:title>ABSTRACT</jats:title> <jats:p> Dengue 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 <jats:italic>in vitro</jats:italic> and in cells by benzothiazole derivatives exhibiting 50% inhibitory concentrations (IC <jats:sub>50</jats:sub> s) 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 <jats:italic>in vitro</jats:italic> 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 IC <jats:sub>50</jats:sub> s in the low-micromolar or submicromolar range in cells. Furthermore, these novel PIs inhibit viral replication at submicromolar concentrations. </jats:p>
Autoren
  • Hongmei Wu
  • Stefanie Bock
  • Mariya Snitko
  • Thilo Berger
  • Thomas Weidner
  • Steven Holloway
  • Manuel Kanitz
  • Wibke E Diederich
  • Holger Steuber
  • Christof Walter
  • Daniela Hofmann
  • Benedikt Weißbrich
  • Ralf Spannaus
  • Eliana G Acosta
  • Ralf Bartenschlager
  • Bernd Engels
  • Tanja Schirmeister
  • Jochen Bodem
DOI
10.1128/aac.03543-14
eISSN
1098-6596
ISSN
0066-4804
Ausgabe der Veröffentlichung
2
Zeitschrift
Antimicrobial Agents and Chemotherapy
Sprache
en
Paginierung
1100 - 1109
Datum der Veröffentlichung
2015
Status
Published
Herausgeber
American Society for Microbiology
Herausgeber URL
http://dx.doi.org/10.1128/aac.03543-14
Datum der Datenerfassung
2022
Titel
Novel Dengue Virus NS2B/NS3 Protease Inhibitors
Ausgabe der Zeitschrift
59

Datenquelle: Crossref

Abstract
Dengue 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.
Addresses
  • Institut für Pharmazie und Biochemie, Johannes Gutenberg-Universität, Mainz, Germany.
Autoren
  • Hongmei Wu
  • Stefanie Bock
  • Mariya Snitko
  • Thilo Berger
  • Thomas Weidner
  • Steven Holloway
  • Manuel Kanitz
  • Wibke E Diederich
  • Holger Steuber
  • Christof Walter
  • Daniela Hofmann
  • Benedikt Weißbrich
  • Ralf Spannaus
  • Eliana G Acosta
  • Ralf Bartenschlager
  • Bernd Engels
  • Tanja Schirmeister
  • Jochen Bodem
DOI
10.1128/aac.03543-14
eISSN
1098-6596
Externe Identifier
  • PubMed Identifier: 25487800
  • PubMed Central ID: PMC4335830
Open access
false
ISSN
0066-4804
Ausgabe der Veröffentlichung
2
Zeitschrift
Antimicrobial agents and chemotherapy
Schlüsselwörter
  • Cell Line
  • Humans
  • Dengue Virus
  • HIV-1
  • Serine Endopeptidases
  • Viral Nonstructural Proteins
  • Protease Inhibitors
  • Antiviral Agents
  • Virus Replication
  • Molecular Docking Simulation
Sprache
eng
Medium
Print-Electronic
Online publication date
2014
Paginierung
1100 - 1109
Datum der Veröffentlichung
2015
Status
Published
Datum der Datenerfassung
2014
Titel
Novel dengue virus NS2B/NS3 protease inhibitors.
Sub types
  • Research Support, Non-U.S. Gov't
  • research-article
  • Journal Article
Ausgabe der Zeitschrift
59

Files

https://aac.asm.org/content/aac/59/2/1100.full.pdf https://europepmc.org/articles/PMC4335830?pdf=render

Datenquelle: Europe PubMed Central

Abstract
Dengue 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.
Autoren
  • Hongmei Wu
  • Stefanie Bock
  • Mariya Snitko
  • Thilo Berger
  • Thomas Weidner
  • Steven Holloway
  • Manuel Kanitz
  • Wibke E Diederich
  • Holger Steuber
  • Christof Walter
  • Daniela Hofmann
  • Benedikt Weißbrich
  • Ralf Spannaus
  • Eliana G Acosta
  • Ralf Bartenschlager
  • Bernd Engels
  • Tanja Schirmeister
  • Jochen Bodem
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/25487800
DOI
10.1128/AAC.03543-14
eISSN
1098-6596
Externe Identifier
  • PubMed Central ID: PMC4335830
Ausgabe der Veröffentlichung
2
Zeitschrift
Antimicrob Agents Chemother
Schlüsselwörter
  • Antiviral Agents
  • Cell Line
  • Dengue Virus
  • HIV-1
  • Humans
  • Molecular Docking Simulation
  • Protease Inhibitors
  • Serine Endopeptidases
  • Viral Nonstructural Proteins
  • Virus Replication
Sprache
eng
Country
United States
Paginierung
1100 - 1109
PII
AAC.03543-14
Datum der Veröffentlichung
2015
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2015
Titel
Novel dengue virus NS2B/NS3 protease inhibitors.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
59

Datenquelle: PubMed

Author's licence
InCopyright
Autoren
  • Hongmei Wu
  • Stefanie Bock
  • Mariya Snitko
  • Thilo Berger
  • Thomas Weidner
  • Steven Holloway
  • Manuel Kanitz
  • Wibke E Diederich
  • Holger Steuber
  • Christof Walter
  • Daniela Hofmann
  • Benedikt Weißbrich
  • Ralf Spannaus
  • Eliana G Acosta
  • Ralf Bartenschlager
  • Bernd Engels
  • Tanja Schirmeister
  • Jochen Bodem
Hosting institution
Universitätsbibliothek Mainz
Sammlungen
  • DFG-OA-Publizieren (2012 - 2017)
Resource version
Published version
DOI
10.1128/AAC.03543-14
Funding acknowledgements
  • DFG, Open Access-Publizieren Universität Mainz / Universitätsmedizin
File(s) embargoed
false
Open access
true
ISSN
1098-6596
Ausgabe der Veröffentlichung
2
Zeitschrift
Antimicrobial agents and chemotherapy
Schlüsselwörter
  • 570 Biowissenschaften
  • 570 Life sciences
Sprache
eng
Open access status
Open Access
Paginierung
1100 - 1109
Datum der Veröffentlichung
2015
Public URL
https://openscience.ub.uni-mainz.de/handle/20.500.12030/8506
Herausgeber
Soc.
Herausgeber URL
http://dx.doi.org/10.1128/AAC.03543-14
Datum der Datenerfassung
2022
Datum, an dem der Datensatz öffentlich gemacht wurde
2022
Zugang
Public
Titel
Novel dengue virus NS2B/NS3 protease inhibitors
Ausgabe der Zeitschrift
59

Files

novel_dengue_virus_ns2bns3_pr-20220913202020725.pdf

Datenquelle: OPENSCIENCE.UB

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