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DOI 10.1038/s42003-022-03737-7

Медицинская библиотека · Communications biology · 2022

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

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, Schubert Robin, Machado Rafael Rahal Guaragna, Candido Erika Donizette, Oliveira Danielle Bruna Leal, Durigon Edison Luiz, Niebling Stephan, Garcia Angelica Struve, Yefanov Oleksandr, Lieske Julia, Gelisio Luca, Domaracky Martin, Middendorf Philipp, Groessler Michael, Trost Fabian, Galchenkova Marina, Mashhour Aida Rahmani, Saouane Sofiane, Hakanpää Johanna, Wolf Markus, Alai Maria Garcia, Turk Dusan, Pearson Arwen R, Chapman Henry N, Hinrichs Winfried, Wrenger Carsten, Meents Alke, Betzel Christian

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Аннотация

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.

Для цитирования: 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, Schubert Robin, Machado Rafael Rahal Guaragna, Candido Erika Donizette, Oliveira Danielle Bruna Leal, Durigon Edison Luiz, Niebling Stephan, Garcia Angelica Struve, Yefanov Oleksandr, Lieske Julia, Gelisio Luca, Domaracky Martin, Middendorf Philipp, Groessler Michael, Trost Fabian, Galchenkova Marina, Mashhour Aida Rahmani, Saouane Sofiane, Hakanpää Johanna, Wolf Markus, Alai Maria Garcia, Turk Dusan, Pearson Arwen R, Chapman Henry N, Hinrichs Winfried, Wrenger Carsten, Meents Alke, Betzel Christian. Antiviral activity of natural phenolic compounds in complex at an allosteric site of SARS-CoV-2 papain-like protease.. Communications biology. 2022. DOI: 10.1038/s42003-022-03737-7.

Предметные рубрики MeSH

Allosteric SiteAntiviral AgentsCoronavirus Papain-Like ProteasesHumansPapainPeptide HydrolasesSARS-CoV-2COVID-19 Drug Treatment
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