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  1. AU="Bardiot, Dorothée"
  2. AU="Kaastra"
  3. AU="Marianne Debré"
  4. AU="Zugasti, Ana"
  5. AU="Zhou, Xunjian"
  6. AU="Montero-Vergara, Jetsy"
  7. AU="Pryce, David"
  8. AU="Stabel, Judith R"
  9. AU=Badgley C E AU=Badgley C E
  10. AU=Riback Joshua A.
  11. AU="Sethi, Ansh"
  12. AU="Tibbo, Meagan E"
  13. AU="Prechtl, Stefan"
  14. AU="Kuanyshbek, Alibek"
  15. AU="Annukka Pasanen"
  16. AU="Yi, Ling Ka"
  17. AU="Kong, Hyejin"
  18. AU="Bilio, João"
  19. AU=Hill Stephen J
  20. AU="Hatayama, Sho"
  21. AU="Ruuskanen, Suvi K"
  22. AU="Kim, Song-Rae"
  23. AU="Mizia-Stec, Katarzyna"
  24. AU="Helen V. Firth"
  25. AU=Giroux Leprieur Etienne
  26. AU="Xinhui Gao"
  27. AU="Christoph Schlapbach"
  28. AU="Akbar, Shayista"
  29. AU="Butler, Eboneé N"
  30. AU="Moura-Alves, Márcio"
  31. AU="Marcet, Ismael"
  32. AU=Eichfelder Sebastian
  33. AU=Timins M E
  34. AU="Weber, Stephan"
  35. AU=Galuska David
  36. AU="Carrieri, Mariella"
  37. AU="Hafkamp, Frederique J"
  38. AU="Jessica M. Perkins"
  39. AU="Tariq, Syeda Sumayya"
  40. AU="Meehan, Rebecca"

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  1. Artikel ; Online: Discovery of JNJ-1802, a First-in-Class Pan-Serotype Dengue Virus NS4B Inhibitor.

    Kesteleyn, Bart / Bonfanti, Jean-François / Bardiot, Dorothée / De Boeck, Benoît / Goethals, Olivia / Kaptein, Suzanne J F / Stoops, Bart / Coesemans, Erwin / Fortin, Jérôme / Muller, Philippe / Doublet, Frédéric / Carlens, Gunter / Koukni, Mohamed / Smets, Wim / Raboisson, Pierre / Chaltin, Patrick / Simmen, Kenny / Loock, Marnix Van / Neyts, Johan /
    Marchand, Arnaud / Jonckers, Tim H M

    Journal of medicinal chemistry

    2024  Band 67, Heft 5, Seite(n) 4063–4082

    Abstract: Dengue is a global public health threat, with about half of the world's population at risk of contracting this mosquito-borne viral disease. Climate change, urbanization, and global travel accelerate the spread of dengue virus (DENV) to new areas, ... ...

    Abstract Dengue is a global public health threat, with about half of the world's population at risk of contracting this mosquito-borne viral disease. Climate change, urbanization, and global travel accelerate the spread of dengue virus (DENV) to new areas, including southern parts of Europe and the US. Currently, no dengue-specific small-molecule antiviral for prophylaxis or treatment is available. Here, we report the discovery of
    Mesh-Begriff(e) Mice ; Humans ; Animals ; Dengue Virus ; Serogroup ; Dengue/drug therapy ; Hydrocarbons, Halogenated ; Indoles
    Chemische Substanzen JNJ-1802 ; Hydrocarbons, Halogenated ; Indoles
    Sprache Englisch
    Erscheinungsdatum 2024-02-28
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/acs.jmedchem.3c02336
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: The Substitutions L50F, E166A, and L167F in SARS-CoV-2 3CLpro Are Selected by a Protease Inhibitor

    Jochmans, Dirk / Liu, Cheng / Donckers, Kim / Stoycheva, Antitsa / Boland, Sandro / Stevens, Sarah K / De Vita, Chloe / Vanmechelen, Bert / Maes, Piet / Trüeb, Bettina / Ebert, Nadine / Thiel, Volker / De Jonghe, Steven / Vangeel, Laura / Bardiot, Dorothée / Jekle, Andreas / Blatt, Lawrence M / Beigelman, Leonid / Symons, Julian A /
    Raboisson, Pierre / Chaltin, Patrick / Marchand, Arnaud / Neyts, Johan / Deval, Jerome / Vandyck, Koen

    mBio

    2023  Band 14, Heft 1, Seite(n) e0281522

    Abstract: The SARS-CoV-2 main protease (3CLpro) has an indispensable role in the viral life cycle and is a therapeutic target for the treatment of COVID-19. The potential of 3CLpro-inhibitors to select for drug-resistant variants needs to be established. Therefore, ...

    Abstract The SARS-CoV-2 main protease (3CLpro) has an indispensable role in the viral life cycle and is a therapeutic target for the treatment of COVID-19. The potential of 3CLpro-inhibitors to select for drug-resistant variants needs to be established. Therefore, SARS-CoV-2 was passaged
    Mesh-Begriff(e) Humans ; Antiviral Agents/pharmacology ; Antiviral Agents/chemistry ; COVID-19 ; Enzyme Inhibitors ; Protease Inhibitors/pharmacology ; Protease Inhibitors/chemistry ; SARS-CoV-2/genetics
    Chemische Substanzen Antiviral Agents ; ensitrelvir (PX665RAA3H) ; Enzyme Inhibitors ; nirmatrelvir and ritonavir drug combination ; Protease Inhibitors ; 3C-like proteinase, SARS-CoV-2 (EC 3.4.22.-)
    Sprache Englisch
    Erscheinungsdatum 2023-01-10
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 2557172-2
    ISSN 2150-7511 ; 2161-2129
    ISSN (online) 2150-7511
    ISSN 2161-2129
    DOI 10.1128/mbio.02815-22
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: Discovery of Acyl-Indole Derivatives as Pan-Serotype Dengue Virus NS4B Inhibitors.

    Kesteleyn, Bart / Bardiot, Dorothée / Bonfanti, Jean-François / De Boeck, Benoît / Goethals, Olivia / Kaptein, Suzanne J F / Stoops, Bart / Coesemans, Erwin / Fortin, Jérôme / Muller, Philippe / Doublet, Frédéric / Carlens, Gunter / Koukni, Mohamed / Smets, Wim / Raboisson, Pierre / Chaltin, Patrick / Simmen, Kenny / Van Loock, Marnix / Neyts, Johan /
    Marchand, Arnaud / Jonckers, Tim H M

    Journal of medicinal chemistry

    2023  Band 66, Heft 13, Seite(n) 8808–8821

    Abstract: In the absence of any approved dengue-specific treatment, the discovery and development of a novel small-molecule antiviral for the prevention or treatment of dengue are critical. We previously reported the identification of a novel series of 3-acyl- ... ...

    Abstract In the absence of any approved dengue-specific treatment, the discovery and development of a novel small-molecule antiviral for the prevention or treatment of dengue are critical. We previously reported the identification of a novel series of 3-acyl-indole derivatives as potent and pan-serotype dengue virus inhibitors. We herein describe our optimization efforts toward preclinical candidates
    Mesh-Begriff(e) Mice ; Animals ; Dengue Virus ; Serogroup ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Dengue/drug therapy ; Indoles/pharmacology ; Indoles/therapeutic use
    Chemische Substanzen Antiviral Agents ; Indoles
    Sprache Englisch
    Erscheinungsdatum 2023-06-30
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/acs.jmedchem.3c00403
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: Dual inhibition of SARS-CoV-2 and human rhinovirus with protease inhibitors in clinical development.

    Liu, Cheng / Boland, Sandro / Scholle, Michael D / Bardiot, Dorothee / Marchand, Arnaud / Chaltin, Patrick / Blatt, Lawrence M / Beigelman, Leonid / Symons, Julian A / Raboisson, Pierre / Gurard-Levin, Zachary A / Vandyck, Koen / Deval, Jerome

    Antiviral research

    2021  Band 187, Seite(n) 105020

    Abstract: The 3-chymotrypsin-like cysteine protease (3CLpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is considered a major target for the discovery of direct antiviral agents. We previously reported the evaluation of SARS-CoV-2 3CLpro ... ...

    Abstract The 3-chymotrypsin-like cysteine protease (3CLpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is considered a major target for the discovery of direct antiviral agents. We previously reported the evaluation of SARS-CoV-2 3CLpro inhibitors in a novel self-assembled monolayer desorption ionization mass spectrometry (SAMDI-MS) enzymatic assay (Gurard-Levin et al., 2020). The assay was further improved by adding the rhinovirus HRV3C protease to the same well as the SARS-CoV-2 3CLpro enzyme. High substrate specificity for each enzyme allowed the proteases to be combined in a single assay reaction without interfering with their individual activities. This novel duplex assay was used to profile a diverse set of reference protease inhibitors. The protease inhibitors were grouped into three categories based on their relative potency against 3CLpro and HRV3C including those that are: equipotent against 3CLpro and HRV3C (GC376 and calpain inhibitor II), selective for 3CLpro (PF-00835231, calpain inhibitor XII, boceprevir), and selective for HRV3C (rupintrivir). Structural analysis showed that the combination of minimal interactions, conformational flexibility, and limited bulk allows GC376 and calpain inhibitor II to potently inhibit both enzymes. In contrast, bulkier compounds interacting more tightly with pockets P2, P3, and P4 due to optimization for a specific target display a more selective inhibition profile. Consistently, the most selective viral protease inhibitors were relatively weak inhibitors of human cathepsin L. Taken together, these results can guide the design of cysteine protease inhibitors that are either virus-specific or retain a broad antiviral spectrum against coronaviruses and rhinoviruses.
    Mesh-Begriff(e) Antiviral Agents/chemistry ; Antiviral Agents/pharmacology ; Binding Sites ; Cathepsin L/metabolism ; Coronavirus 3C Proteases/antagonists & inhibitors ; Drug Discovery ; Glycoproteins/pharmacology ; Humans ; Kinetics ; Models, Molecular ; Protease Inhibitors/chemistry ; Protease Inhibitors/pharmacology ; Pyrrolidines/pharmacology ; Rhinovirus/drug effects ; SARS-CoV-2/drug effects ; Sulfonic Acids
    Chemische Substanzen Antiviral Agents ; Glycoproteins ; Protease Inhibitors ; Pyrrolidines ; Sulfonic Acids ; calpain inhibitors ; CTSL protein, human (EC 3.4.22.15) ; Cathepsin L (EC 3.4.22.15) ; Coronavirus 3C Proteases (EC 3.4.22.28) ; GC376 (H1NMJ5XDG5)
    Sprache Englisch
    Erscheinungsdatum 2021-01-27
    Erscheinungsland Netherlands
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 306628-9
    ISSN 1872-9096 ; 0166-3542
    ISSN (online) 1872-9096
    ISSN 0166-3542
    DOI 10.1016/j.antiviral.2021.105020
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: Differential antiviral activities of respiratory syncytial virus (RSV) inhibitors in human airway epithelium.

    Mirabelli, Carmen / Jaspers, Martine / Boon, Mieke / Jorissen, Mark / Koukni, Mohamed / Bardiot, Dorothée / Chaltin, Patrick / Marchand, Arnaud / Neyts, Johan / Jochmans, Dirk

    The Journal of antimicrobial chemotherapy

    2018  Band 73, Heft 7, Seite(n) 1823–1829

    Abstract: Objectives: We report the use of reconstituted 3D human airway epithelium cells (HuAECs) of bronchial origin in an air-liquid interface to study respiratory syncytial virus (RSV) infection and to assess the efficacy of RSV inhibitors in (pre-)clinical ... ...

    Abstract Objectives: We report the use of reconstituted 3D human airway epithelium cells (HuAECs) of bronchial origin in an air-liquid interface to study respiratory syncytial virus (RSV) infection and to assess the efficacy of RSV inhibitors in (pre-)clinical development.
    Methods: HuAECs were infected with RSV-A Long strain (0.01 CCID50/cell, where CCID50 represents 50% cell culture infectious dose in HEp2 cells) on the apical compartment of the culture. At the time of infection or at 1 or 3 days post-infection, selected inhibitors were added and refreshed daily on the basal compartment of the culture. Viral shedding was followed up by apical washes collected daily and quantifying viral RNA by RT-qPCR.
    Results: RSV-A replicates efficiently in HuAECs and viral RNA is shed for weeks after infection. RSV infection reduces the ciliary beat frequency of the ciliated cells as of 4 days post-infection, with complete ciliary dyskinesia observed by day 10. Treatment with RSV fusion inhibitors resulted in an antiviral effect only when added at the time of infection. In contrast, the use of replication inhibitors (both nucleoside and non-nucleoside) elicited a marked antiviral effect even when the start of treatment was delayed until 1 day or even 3 days after infection. Levels of the inflammation marker RANTES (mRNA) increased ∼200-fold in infected, untreated cultures (at 3 weeks post-infection), but levels were comparable to those of uninfected cultures in the presence of PC786, an RSV replication inhibitor, suggesting that an efficient antiviral treatment might inhibit virus-induced inflammation in this model.
    Conclusions: Overall, HuAECs offer a robust and physiologically relevant model to study RSV replication and to assess the efficacy of antiviral compounds.
    Mesh-Begriff(e) Antiviral Agents/pharmacology ; Cell Culture Techniques ; Drug Evaluation, Preclinical ; Epithelial Cells/virology ; Humans ; Organ Culture Techniques ; RNA, Viral/genetics ; Respiratory Mucosa/virology ; Respiratory Syncytial Virus Infections/drug therapy ; Respiratory Syncytial Virus, Human/drug effects ; Respiratory Syncytial Virus, Human/genetics ; Spiro Compounds/pharmacology ; Virus Replication/drug effects
    Chemische Substanzen Antiviral Agents ; RNA, Viral ; Spiro Compounds ; PC786 (MC0MD9J0F4)
    Sprache Englisch
    Erscheinungsdatum 2018-03-05
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 191709-2
    ISSN 1460-2091 ; 0305-7453
    ISSN (online) 1460-2091
    ISSN 0305-7453
    DOI 10.1093/jac/dky089
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; Online: Publisher Correction: A pan-serotype dengue virus inhibitor targeting the NS3-NS4B interaction.

    Kaptein, Suzanne J F / Goethals, Olivia / Kiemel, Dominik / Marchand, Arnaud / Kesteleyn, Bart / Bonfanti, Jean-François / Bardiot, Dorothée / Stoops, Bart / Jonckers, Tim H M / Dallmeier, Kai / Geluykens, Peggy / Thys, Kim / Crabbe, Marjolein / Chatel-Chaix, Laurent / Münster, Max / Querat, Gilles / Touret, Franck / de Lamballerie, Xavier / Raboisson, Pierre /
    Simmen, Kenny / Chaltin, Patrick / Bartenschlager, Ralf / Van Loock, Marnix / Neyts, Johan

    Nature

    2021  Band 599, Heft 7883, Seite(n) E2

    Sprache Englisch
    Erscheinungsdatum 2021-10-20
    Erscheinungsland England
    Dokumenttyp Published Erratum
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/s41586-021-04123-9
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  7. Artikel ; Online: A pan-serotype dengue virus inhibitor targeting the NS3-NS4B interaction.

    Kaptein, Suzanne J F / Goethals, Olivia / Kiemel, Dominik / Marchand, Arnaud / Kesteleyn, Bart / Bonfanti, Jean-François / Bardiot, Dorothée / Stoops, Bart / Jonckers, Tim H M / Dallmeier, Kai / Geluykens, Peggy / Thys, Kim / Crabbe, Marjolein / Chatel-Chaix, Laurent / Münster, Max / Querat, Gilles / Touret, Franck / de Lamballerie, Xavier / Raboisson, Pierre /
    Simmen, Kenny / Chaltin, Patrick / Bartenschlager, Ralf / Van Loock, Marnix / Neyts, Johan

    Nature

    2021  Band 598, Heft 7881, Seite(n) 504–509

    Abstract: Dengue virus causes approximately 96 million symptomatic infections annually, manifesting as dengue fever or occasionally as severe ... ...

    Abstract Dengue virus causes approximately 96 million symptomatic infections annually, manifesting as dengue fever or occasionally as severe dengue
    Mesh-Begriff(e) Animals ; Antiviral Agents/pharmacokinetics ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Dengue/drug therapy ; Dengue/virology ; Dengue Virus/classification ; Dengue Virus/drug effects ; Dengue Virus/genetics ; Dengue Virus/metabolism ; Disease Models, Animal ; Female ; Male ; Membrane Proteins/antagonists & inhibitors ; Membrane Proteins/metabolism ; Mice ; RNA Helicases/antagonists & inhibitors ; RNA Helicases/metabolism ; Serine Endopeptidases/metabolism ; Viral Load/drug effects ; Viral Nonstructural Proteins/antagonists & inhibitors ; Viral Nonstructural Proteins/metabolism ; Viremia/drug therapy ; Viremia/virology ; Virus Replication/drug effects
    Chemische Substanzen Antiviral Agents ; Membrane Proteins ; NS3 protein, flavivirus ; NS4B protein, Dengue virus ; Viral Nonstructural Proteins ; Serine Endopeptidases (EC 3.4.21.-) ; RNA Helicases (EC 3.6.4.13)
    Sprache Englisch
    Erscheinungsdatum 2021-10-06
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/s41586-021-03990-6
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  8. Artikel ; Online: ALG-097111, a potent and selective SARS-CoV-2 3-chymotrypsin-like cysteine protease inhibitor exhibits in vivo efficacy in a Syrian Hamster model.

    Vandyck, Koen / Abdelnabi, Rana / Gupta, Kusum / Jochmans, Dirk / Jekle, Andreas / Deval, Jerome / Misner, Dinah / Bardiot, Dorothée / Foo, Caroline S / Liu, Cheng / Ren, Suping / Beigelman, Leonid / Blatt, Lawrence M / Boland, Sandro / Vangeel, Laura / Dejonghe, Steven / Chaltin, Patrick / Marchand, Arnaud / Serebryany, Vladimir /
    Stoycheva, Antitsa / Chanda, Sushmita / Symons, Julian A / Raboisson, Pierre / Neyts, Johan

    Biochemical and biophysical research communications

    2021  Band 555, Seite(n) 134–139

    Abstract: There is an urgent need for antivirals targeting the SARS-CoV-2 virus to fight the current COVID-19 pandemic. The SARS-CoV-2 main protease (3CLpro) represents a promising target for antiviral therapy. The lack of selectivity for some of the reported ... ...

    Abstract There is an urgent need for antivirals targeting the SARS-CoV-2 virus to fight the current COVID-19 pandemic. The SARS-CoV-2 main protease (3CLpro) represents a promising target for antiviral therapy. The lack of selectivity for some of the reported 3CLpro inhibitors, specifically versus cathepsin L, raises potential safety and efficacy concerns. ALG-097111 potently inhibited SARS-CoV-2 3CLpro (IC
    Mesh-Begriff(e) Amides/pharmacokinetics ; Amides/pharmacology ; Animals ; COVID-19/drug therapy ; COVID-19/virology ; Cathepsin L/antagonists & inhibitors ; Cell Line ; Coronavirus 3C Proteases/antagonists & inhibitors ; Cricetinae ; Cysteine Proteinase Inhibitors/pharmacokinetics ; Cysteine Proteinase Inhibitors/pharmacology ; Disease Models, Animal ; Female ; Humans ; Inhibitory Concentration 50 ; Male ; Mesocricetus/virology ; Reproducibility of Results ; SARS-CoV-2/drug effects ; SARS-CoV-2/enzymology ; SARS-CoV-2/growth & development ; Serine Endopeptidases ; Substrate Specificity ; Virus Replication/drug effects
    Chemische Substanzen ALG-097111 ; Amides ; Cysteine Proteinase Inhibitors ; Serine Endopeptidases (EC 3.4.21.-) ; TMPRSS2 protein, human (EC 3.4.21.-) ; Cathepsin L (EC 3.4.22.15) ; Coronavirus 3C Proteases (EC 3.4.22.28)
    Sprache Englisch
    Erscheinungsdatum 2021-03-26
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 205723-2
    ISSN 1090-2104 ; 0006-291X ; 0006-291X
    ISSN (online) 1090-2104 ; 0006-291X
    ISSN 0006-291X
    DOI 10.1016/j.bbrc.2021.03.096
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  9. Artikel ; Online: Discovery of Indole Derivatives as Novel and Potent Dengue Virus Inhibitors.

    Bardiot, Dorothée / Koukni, Mohamed / Smets, Wim / Carlens, Gunter / McNaughton, Michael / Kaptein, Suzanne / Dallmeier, Kai / Chaltin, Patrick / Neyts, Johan / Marchand, Arnaud

    Journal of medicinal chemistry

    2018  Band 61, Heft 18, Seite(n) 8390–8401

    Abstract: 3-Acyl-indole derivative 1 was identified as a novel dengue virus (DENV) inhibitor from a DENV serotype 2 (DENV-2) phenotypic antiviral screen. Extensive SAR studies led to the discovery of new derivatives with improved DENV-2 potency as well as activity ...

    Abstract 3-Acyl-indole derivative 1 was identified as a novel dengue virus (DENV) inhibitor from a DENV serotype 2 (DENV-2) phenotypic antiviral screen. Extensive SAR studies led to the discovery of new derivatives with improved DENV-2 potency as well as activity in nanomolar to micromolar range against the other DENV serotypes. In addition to the potency, physicochemical properties and metabolic stability in rat and human microsomes were improved during the optimization process. Chiral separation of the racemic mixtures showed a clear preference for one of the two enantiomers. Furthermore, rat pharmacokinetics of two compounds will be discussed in more detail, demonstrating the potential of this new series of pan-serotype-DENV inhibitors.
    Mesh-Begriff(e) Animals ; Antiviral Agents/chemistry ; Antiviral Agents/pharmacology ; Cercopithecus aethiops ; Dengue/drug therapy ; Dengue/virology ; Dengue Virus/classification ; Dengue Virus/drug effects ; Drug Design ; Drug Discovery ; Humans ; Indoles/chemistry ; Microsomes, Liver/drug effects ; Microsomes, Liver/metabolism ; Models, Molecular ; Molecular Structure ; Protein Conformation ; Rats ; Structure-Activity Relationship ; Vero Cells
    Chemische Substanzen Antiviral Agents ; Indoles
    Sprache Englisch
    Erscheinungsdatum 2018-09-12
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/acs.jmedchem.8b00913
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  10. Artikel ; Online: Synthesis, Structure-Activity Relationships, and Antiviral Profiling of 1-Heteroaryl-2-Alkoxyphenyl Analogs as Inhibitors of SARS-CoV-2 Replication.

    Bardiot, Dorothée / Vangeel, Laura / Koukni, Mohamed / Arzel, Philippe / Zwaagstra, Marleen / Lyoo, Heyrhyoung / Wanningen, Patrick / Ahmad, Shamshad / Zhang, Linlin / Sun, Xinyuanyuan / Delpal, Adrien / Eydoux, Cecilia / Guillemot, Jean-Claude / Lescrinier, Eveline / Klaassen, Hugo / Leyssen, Pieter / Jochmans, Dirk / Castermans, Karolien / Hilgenfeld, Rolf /
    Robinson, Colin / Decroly, Etienne / Canard, Bruno / Snijder, Eric J / van Hemert, Martijn J / van Kuppeveld, Frank / Chaltin, Patrick / Neyts, Johan / De Jonghe, Steven / Marchand, Arnaud

    Molecules (Basel, Switzerland)

    2022  Band 27, Heft 3

    Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has led to a pandemic, that continues to be a huge public health burden. Despite the availability of vaccines, there is still a need for small-molecule ... ...

    Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has led to a pandemic, that continues to be a huge public health burden. Despite the availability of vaccines, there is still a need for small-molecule antiviral drugs. In an effort to identify novel and drug-like hit matter that can be used for subsequent hit-to-lead optimization campaigns, we conducted a high-throughput screening of a 160 K compound library against SARS-CoV-2, yielding a 1-heteroaryl-2-alkoxyphenyl analog as a promising hit. Antiviral profiling revealed this compound was active against various beta-coronaviruses and preliminary mode-of-action experiments demonstrated that it interfered with viral entry. A systematic structure-activity relationship (SAR) study demonstrated that a 3- or 4-pyridyl moiety on the oxadiazole moiety is optimal, whereas the oxadiazole can be replaced by various other heteroaromatic cycles. In addition, the alkoxy group tolerates some structural diversity.
    Mesh-Begriff(e) Animals ; Antiviral Agents/chemistry ; Antiviral Agents/pharmacology ; Chlorocebus aethiops ; Heterocyclic Compounds/pharmacology ; High-Throughput Screening Assays ; Microbial Sensitivity Tests ; SARS-CoV-2/drug effects ; Structure-Activity Relationship ; Vero Cells ; Virus Replication/drug effects
    Chemische Substanzen Antiviral Agents ; Heterocyclic Compounds
    Sprache Englisch
    Erscheinungsdatum 2022-02-04
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules27031052
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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