%0 Journal Article
%A Srinivasan, Vasundara
%A Brognaro, Hévila
%A Prabhu, Prince R.
%A de Souza, Edmarcia Elisa
%A Guenther, Sebastian
%A Reinke, Patrick
%A Lane, Thomas
%A Ginn, Helen
%A Han, Huijong
%A Ewert, Wiebke
%A Sprenger, Janina
%A Koua, Faisal H. M.
%A Falke, Sven
%A Werner, Nadine
%A Andaleeb, Hina
%A Ullah, Najeeb
%A Franca, Bruno Alves
%A Wang, Mengying
%A Barra, Angelica
%A Perbandt, Markus
%A Schwinzer, Martin
%A Schmidt, Christina
%A Brings, Lea
%A Lorenzen, Kristina
%A Schubert, Robin
%A Machado, Rafael Rahal Guaragna
%A Candido, Erika Donizette
%A Oliveira, Danielle Bruna Leal
%A Durigon, Edison Luiz
%A Niebling, Stephan
%A Garcia, Angelica Struve
%A Yefanov, Oleksandr
%A Lieske, Julia
%A Gelisio, Luca
%A Domaracky, Martin
%A Middendorf, Philipp
%A Groessler, Michael
%A Trost, Fabian
%A Galchenkova, Marina
%A Mashhour, Aida Rahmani
%A Saouane, Sofiane
%A Hakanpää, Johanna
%A Wolf, Markus
%A Alai, Maria Garcia
%A Turk, Dusan
%A Pearson, Arwen
%A Chapman, Henry N.
%A Hinrichs, Winfried
%A Wrenger, Carsten
%A Meents, Alke
%A Betzel, Christian
%T Antiviral activity of natural phenolic compounds in complex at an allosteric site of SARS-CoV-2 papain-like protease
%J Communications biology
%V 5
%N 1
%@ 2399-3642
%C London
%I Springer Nature
%M PUBDB-2022-04889
%P 805
%D 2022
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:35953531
%U <Go to ISI:>//WOS:000839651500002
%R 10.1038/s42003-022-03737-7
%U https://bib-pubdb1.desy.de/record/482648