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Srinivasan, Vasundara; Brognaro, Hévila; Prabhu, Prince R.; de Souza, Edmarcia Elisa; Günther, Sebastian; Reinke, Patrick Y. A.; Lane, Thomas J.; Ginn, Helen; Han, Huijong; Ewert, Wiebke; Sprenger, Janina; Koua, Faisal H. M.; Falke, Sven; Werner, Nadine; Andaleeb, Hina; Ullah, Najeeb; Franca, Bruno Alves; Wang, Mengying; Barra, Angélica Luana C.; Perbandt, Markus; Schwinzer, Martin; Schmidt, Christina; Brings, Lea; Lorenzen, Kristina; [...]

Antiviral activity of natural phenolic compounds in complex at an allosteric site of SARS-CoV-2 papain-like protease

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  • Media type: E-Article
  • Title: Antiviral activity of natural phenolic compounds in complex at an allosteric site of SARS-CoV-2 papain-like protease
  • Contributor: Srinivasan, Vasundara; Brognaro, Hévila; Prabhu, Prince R.; de Souza, Edmarcia Elisa; Günther, Sebastian; Reinke, Patrick Y. A.; Lane, Thomas J.; Ginn, Helen; Han, Huijong; Ewert, Wiebke; Sprenger, Janina; Koua, Faisal H. M.; Falke, Sven; Werner, Nadine; Andaleeb, Hina; Ullah, Najeeb; Franca, Bruno Alves; Wang, Mengying; Barra, Angélica Luana C.; Perbandt, Markus; Schwinzer, Martin; Schmidt, Christina; Brings, Lea; Lorenzen, Kristina; [...]
  • imprint: Springer Science and Business Media LLC, 2022
  • Published in: Communications Biology
  • Language: English
  • DOI: 10.1038/s42003-022-03737-7
  • ISSN: 2399-3642
  • Keywords: General Agricultural and Biological Sciences ; General Biochemistry, Genetics and Molecular Biology ; Medicine (miscellaneous)
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:p>SARS-CoV-2 papain-like protease (PLpro) covers multiple functions. Beside the cysteine-protease activity, facilitating cleavage of the viral polypeptide chain, PLpro has the additional and vital function of removing ubiquitin and ISG15 (Interferon-stimulated gene 15) from host-cell proteins to support coronaviruses in evading the host’s innate immune responses. We identified three phenolic compounds bound to PLpro, preventing essential molecular interactions to ISG15 by screening a natural compound library. The compounds identified by X-ray screening and complexed to PLpro demonstrate clear inhibition of PLpro in a deISGylation activity assay. Two compounds exhibit distinct antiviral activity in Vero cell line assays and one inhibited a cytopathic effect in non-cytotoxic concentration ranges. In the context of increasing PLpro mutations in the evolving new variants of SARS-CoV-2, the natural compounds we identified may also reinstate the antiviral immune response processes of the host that are down-regulated in COVID-19 infections.</jats:p>
  • Access State: Open Access