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  1. AU="Melore, Schuyler"
  2. AU="Ardito, Alan A"
  3. AU=Meyer Jacob
  4. AU="Nataly Ruiz-Quiñones"
  5. AU="Núñez, Marcela"
  6. AU="Poilvache, Hervé"
  7. AU="Manavalan, Preeti"
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  9. AU=Kim Seong Eun
  10. AU=Leventoglu Sezai
  11. AU="Yang, Hengquan"
  12. AU="Champion, Patricia A DiGiuseppe"
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  14. AU="Charleston, Bryan"
  15. AU="Busch, Volker"
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  17. AU="Obrenović-Kirćanski Biljana"
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  20. AU="Saunders, Gary I"
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  37. AU="Midulla, Martina"
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  39. AU="Pritchard, Jonathan"
  40. AU="Memeo, Lorenzo"
  41. AU="Taylan, Gokay"
  42. AU="Tijssen, Robert J. W."
  43. AU="Silva, Marcelina Jasmine"
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  1. Artikel ; Online: Inhibitors of Coronavirus 3CL Proteases Protect Cells from Protease-Mediated Cytotoxicity.

    Resnick, Samuel J / Iketani, Sho / Hong, Seo Jung / Zask, Arie / Liu, Hengrui / Kim, Sungsoo / Melore, Schuyler / Lin, Fang-Yu / Nair, Manoj S / Huang, Yaoxing / Lee, Sumin / Tay, Nicholas E S / Rovis, Tomislav / Yang, Hee Won / Xing, Li / Stockwell, Brent R / Ho, David D / Chavez, Alejandro

    Journal of virology

    2021  Band 95, Heft 14, Seite(n) e0237420

    Abstract: We describe a mammalian cell-based assay to identify coronavirus 3CL protease (3CLpro) inhibitors. This assay is based on rescuing protease-mediated cytotoxicity and does not require live virus. By enabling the facile testing of compounds across a range ... ...

    Abstract We describe a mammalian cell-based assay to identify coronavirus 3CL protease (3CLpro) inhibitors. This assay is based on rescuing protease-mediated cytotoxicity and does not require live virus. By enabling the facile testing of compounds across a range of 15 distantly related coronavirus 3CLpro enzymes, we identified compounds with broad 3CLpro-inhibitory activity. We also adapted the assay for use in compound screening and in doing so uncovered additional severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3CLpro inhibitors. We observed strong concordance between data emerging from this assay and those obtained from live-virus testing. The reported approach democratizes the testing of 3CLpro inhibitors by developing a simplified method for identifying coronavirus 3CLpro inhibitors that can be used by the majority of laboratories, rather than the few with extensive biosafety infrastructure. We identified two lead compounds, GC376 and compound 4, with broad activity against all 3CL proteases tested, including 3CLpro enzymes from understudied zoonotic coronaviruses.
    Mesh-Begriff(e) COVID-19/drug therapy ; COVID-19/enzymology ; Coronavirus 3C Proteases/antagonists & inhibitors ; Coronavirus 3C Proteases/chemistry ; Coronavirus 3C Proteases/metabolism ; Cysteine Proteinase Inhibitors/chemistry ; Cysteine Proteinase Inhibitors/pharmacology ; HEK293 Cells ; Humans ; SARS-CoV-2/enzymology
    Chemische Substanzen Cysteine Proteinase Inhibitors ; Coronavirus 3C Proteases (EC 3.4.22.28)
    Sprache Englisch
    Erscheinungsdatum 2021-06-24
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80174-4
    ISSN 1098-5514 ; 0022-538X
    ISSN (online) 1098-5514
    ISSN 0022-538X
    DOI 10.1128/JVI.02374-20
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel: A simplified cell-based assay to identify coronavirus 3CL protease inhibitors.

    Resnick, Samuel J / Iketani, Sho / Hong, Seo Jung / Zask, Arie / Liu, Hengrui / Kim, Sungsoo / Melore, Schuyler / Nair, Manoj S / Huang, Yaoxing / Tay, Nicholas E S / Rovis, Tomislav / Yang, Hee Won / Stockwell, Brent R / Ho, David D / Chavez, Alejandro

    bioRxiv : the preprint server for biology

    2020  

    Abstract: We describe a mammalian cell-based assay capable of identifying coronavirus 3CL protease (3CLpro) inhibitors without requiring the use of live virus. By enabling the facile testing of compounds across a range of coronavirus 3CLpro enzymes, including the ... ...

    Abstract We describe a mammalian cell-based assay capable of identifying coronavirus 3CL protease (3CLpro) inhibitors without requiring the use of live virus. By enabling the facile testing of compounds across a range of coronavirus 3CLpro enzymes, including the one from SARS-CoV-2, we are able to quickly identify compounds with broad or narrow spectra of activity. We further demonstrate the utility of our approach by performing a curated compound screen along with structure-activity profiling of a series of small molecules to identify compounds with antiviral activity. Throughout these studies, we observed concordance between data emerging from this assay and from live virus assays. By democratizing the testing of 3CL inhibitors to enable screening in the majority of laboratories rather than the few with extensive biosafety infrastructure, we hope to expedite the search for coronavirus 3CL protease inhibitors, to address the current epidemic and future ones that will inevitably arise.
    Schlagwörter covid19
    Sprache Englisch
    Erscheinungsdatum 2020-08-29
    Erscheinungsland United States
    Dokumenttyp Preprint
    DOI 10.1101/2020.08.29.272864
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: A simplified cell-based assay to identify coronavirus 3CL protease inhibitors

    Resnick, Samuel J / Iketani, Sho / Hong, Seo Jung / Zask, Arie / Liu, Hengrui / Kim, Sungsoo / Melore, Schuyler / Nair, Manoj S / Huang, Yaoxing / Tay, Nicholas E S / Rovis, Tomislav / Yang, Hee Won / Stockwell, Brent R / Ho, David D / Chavez, Alejandro

    bioRxiv

    Abstract: We describe a mammalian cell-based assay capable of identifying coronavirus 3CL protease (3CLpro) inhibitors without requiring the use of live virus. By enabling the facile testing of compounds across a range of coronavirus 3CLpro enzymes, including the ... ...

    Abstract We describe a mammalian cell-based assay capable of identifying coronavirus 3CL protease (3CLpro) inhibitors without requiring the use of live virus. By enabling the facile testing of compounds across a range of coronavirus 3CLpro enzymes, including the one from SARS-CoV-2, we are able to quickly identify compounds with broad or narrow spectra of activity. We further demonstrate the utility of our approach by performing a curated compound screen along with structure-activity profiling of a series of small molecules to identify compounds with antiviral activity. Throughout these studies, we observed concordance between data emerging from this assay and from live virus assays. By democratizing the testing of 3CL inhibitors to enable screening in the majority of laboratories rather than the few with extensive biosafety infrastructure, we hope to expedite the search for coronavirus 3CL protease inhibitors, to address the current epidemic and future ones that will inevitably arise.
    Schlagwörter covid19
    Sprache Englisch
    Erscheinungsdatum 2020-08-29
    Verlag Cold Spring Harbor Laboratory
    Dokumenttyp Artikel ; Online
    DOI 10.1101/2020.08.29.272864
    Datenquelle COVID19

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