Antiviral activity of natural phenolic compounds in complex at an allosteric site of SARS-CoV-2 papain-like protease
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Published:2022-08-11
Issue:1
Volume:5
Page:
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ISSN:2399-3642
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Container-title:Communications Biology
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language:en
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Short-container-title:Commun Biol
Author:
Srinivasan VasundaraORCID, Brognaro Hévila, Prabhu Prince R., de Souza Edmarcia Elisa, Günther SebastianORCID, Reinke Patrick Y. A., Lane Thomas J.ORCID, Ginn Helen, Han Huijong, Ewert WiebkeORCID, Sprenger Janina, Koua Faisal H. M.ORCID, Falke Sven, Werner Nadine, Andaleeb Hina, Ullah NajeebORCID, Franca Bruno Alves, Wang Mengying, Barra Angélica Luana C.ORCID, Perbandt MarkusORCID, Schwinzer Martin, Schmidt ChristinaORCID, Brings Lea, Lorenzen Kristina, Schubert RobinORCID, Machado Rafael Rahal Guaragna, Candido Erika DonizetteORCID, Oliveira Danielle Bruna LealORCID, Durigon Edison Luiz, Niebling StephanORCID, Garcia Angelica Struve, Yefanov Oleksandr, Lieske JuliaORCID, Gelisio LucaORCID, Domaracky MartinORCID, Middendorf Philipp, Groessler Michael, Trost FabianORCID, Galchenkova Marina, Mashhour Aida Rahmani, Saouane SofianeORCID, Hakanpää Johanna, Wolf Markus, Alai Maria Garcia, Turk DusanORCID, Pearson Arwen R.ORCID, Chapman Henry N., Hinrichs WinfriedORCID, Wrenger CarstenORCID, Meents AlkeORCID, Betzel ChristianORCID
Abstract
AbstractSARS-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.
Publisher
Springer Science and Business Media LLC
Subject
General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)
Reference71 articles.
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