TY  - JOUR
AU  - Srinivasan, Vasundara
AU  - Brognaro, Hévila
AU  - Prabhu, Prince R.
AU  - de Souza, Edmarcia Elisa
AU  - Guenther, Sebastian
AU  - Reinke, Patrick
AU  - Lane, Thomas
AU  - Ginn, Helen
AU  - Han, Huijong
AU  - Ewert, Wiebke
AU  - Sprenger, Janina
AU  - Koua, Faisal H. M.
AU  - Falke, Sven
AU  - Werner, Nadine
AU  - Andaleeb, Hina
AU  - Ullah, Najeeb
AU  - Franca, Bruno Alves
AU  - Wang, Mengying
AU  - Barra, Angelica
AU  - Perbandt, Markus
AU  - Schwinzer, Martin
AU  - Schmidt, Christina
AU  - Brings, Lea
AU  - Lorenzen, Kristina
AU  - Schubert, Robin
AU  - Machado, Rafael Rahal Guaragna
AU  - Candido, Erika Donizette
AU  - Oliveira, Danielle Bruna Leal
AU  - Durigon, Edison Luiz
AU  - Niebling, Stephan
AU  - Garcia, Angelica Struve
AU  - Yefanov, Oleksandr
AU  - Lieske, Julia
AU  - Gelisio, Luca
AU  - Domaracky, Martin
AU  - Middendorf, Philipp
AU  - Groessler, Michael
AU  - Trost, Fabian
AU  - Galchenkova, Marina
AU  - Mashhour, Aida Rahmani
AU  - Saouane, Sofiane
AU  - Hakanpää, Johanna
AU  - Wolf, Markus
AU  - Alai, Maria Garcia
AU  - Turk, Dusan
AU  - Pearson, Arwen
AU  - Chapman, Henry N.
AU  - Hinrichs, Winfried
AU  - Wrenger, Carsten
AU  - Meents, Alke
AU  - Betzel, Christian
TI  - Antiviral activity of natural phenolic compounds in complex at an allosteric site of SARS-CoV-2 papain-like protease
JO  - Communications biology
VL  - 5
IS  - 1
SN  - 2399-3642
CY  - London
PB  - Springer Nature
M1  - PUBDB-2022-04889
SP  - 805
PY  - 2022
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:35953531
UR  - <Go to ISI:>//WOS:000839651500002
DO  - DOI:10.1038/s42003-022-03737-7
UR  - https://bib-pubdb1.desy.de/record/482648
ER  -