tetano
Editor, Senior Moderator
Commun Biol
. 2022 Aug 11;5(1):805.
doi: 10.1038/s42003-022-03737-7.
Antiviral activity of natural phenolic compounds in complex at an allosteric site of SARS-CoV-2 papain-like protease
Vasundara Srinivasan[SUP] 1 [/SUP], Hévila Brognaro[SUP] 2 [/SUP], Prince R Prabhu[SUP] 2 3 [/SUP], Edmarcia Elisa de Souza[SUP] 4 [/SUP], Sebastian Günther[SUP] 5 [/SUP], Patrick Y A Reinke[SUP] 5 [/SUP], Thomas J Lane[SUP] 3 5 [/SUP], Helen Ginn[SUP] 6 [/SUP], Huijong Han[SUP] 7 [/SUP], Wiebke Ewert[SUP] 5 [/SUP], Janina Sprenger[SUP] 5 [/SUP], Faisal H M Koua[SUP] 5 [/SUP], Sven Falke[SUP] 2 5 [/SUP], Nadine Werner[SUP] 2 [/SUP], Hina Andaleeb[SUP] 2 8 [/SUP], Najeeb Ullah[SUP] 2 8 [/SUP], Bruno Alves Franca[SUP] 2 [/SUP], Mengying Wang[SUP] 2 [/SUP], Angélica Luana C Barra[SUP] 2 9 [/SUP], Markus Perbandt[SUP] 2 [/SUP], Martin Schwinzer[SUP] 2 [/SUP], Christina Schmidt[SUP] 7 [/SUP], Lea Brings[SUP] 7 [/SUP], Kristina Lorenzen[SUP] 7 [/SUP], Robin Schubert[SUP] 7 [/SUP], Rafael Rahal Guaragna Machado[SUP] 10 [/SUP], Erika Donizette Candido[SUP] 10 [/SUP], Danielle Bruna Leal Oliveira[SUP] 10 11 [/SUP], Edison Luiz Durigon[SUP] 10 12 [/SUP], Stephan Niebling[SUP] 13 [/SUP], Angelica Struve Garcia[SUP] 13 [/SUP], Oleksandr Yefanov[SUP] 5 [/SUP], Julia Lieske[SUP] 5 [/SUP], Luca Gelisio[SUP] 5 [/SUP], Martin Domaracky[SUP] 5 [/SUP], Philipp Middendorf[SUP] 5 [/SUP], Michael Groessler[SUP] 5 [/SUP], Fabian Trost[SUP] 5 [/SUP], Marina Galchenkova[SUP] 5 [/SUP], Aida Rahmani Mashhour[SUP] 5 [/SUP], Sofiane Saouane[SUP] 14 [/SUP], Johanna Hakanpää[SUP] 14 [/SUP], Markus Wolf[SUP] 15 [/SUP], Maria Garcia Alai[SUP] 13 [/SUP], Dusan Turk[SUP] 16 17 [/SUP], Arwen R Pearson[SUP] 3 18 [/SUP], Henry N Chapman[SUP] 3 5 19 [/SUP], Winfried Hinrichs[SUP] 20 [/SUP], Carsten Wrenger[SUP] 4 [/SUP], Alke Meents[SUP] 5 [/SUP], Christian Betzel[SUP] 21 22 [/SUP]
Affiliations
Abstract
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.
. 2022 Aug 11;5(1):805.
doi: 10.1038/s42003-022-03737-7.
Antiviral activity of natural phenolic compounds in complex at an allosteric site of SARS-CoV-2 papain-like protease
Vasundara Srinivasan[SUP] 1 [/SUP], Hévila Brognaro[SUP] 2 [/SUP], Prince R Prabhu[SUP] 2 3 [/SUP], Edmarcia Elisa de Souza[SUP] 4 [/SUP], Sebastian Günther[SUP] 5 [/SUP], Patrick Y A Reinke[SUP] 5 [/SUP], Thomas J Lane[SUP] 3 5 [/SUP], Helen Ginn[SUP] 6 [/SUP], Huijong Han[SUP] 7 [/SUP], Wiebke Ewert[SUP] 5 [/SUP], Janina Sprenger[SUP] 5 [/SUP], Faisal H M Koua[SUP] 5 [/SUP], Sven Falke[SUP] 2 5 [/SUP], Nadine Werner[SUP] 2 [/SUP], Hina Andaleeb[SUP] 2 8 [/SUP], Najeeb Ullah[SUP] 2 8 [/SUP], Bruno Alves Franca[SUP] 2 [/SUP], Mengying Wang[SUP] 2 [/SUP], Angélica Luana C Barra[SUP] 2 9 [/SUP], Markus Perbandt[SUP] 2 [/SUP], Martin Schwinzer[SUP] 2 [/SUP], Christina Schmidt[SUP] 7 [/SUP], Lea Brings[SUP] 7 [/SUP], Kristina Lorenzen[SUP] 7 [/SUP], Robin Schubert[SUP] 7 [/SUP], Rafael Rahal Guaragna Machado[SUP] 10 [/SUP], Erika Donizette Candido[SUP] 10 [/SUP], Danielle Bruna Leal Oliveira[SUP] 10 11 [/SUP], Edison Luiz Durigon[SUP] 10 12 [/SUP], Stephan Niebling[SUP] 13 [/SUP], Angelica Struve Garcia[SUP] 13 [/SUP], Oleksandr Yefanov[SUP] 5 [/SUP], Julia Lieske[SUP] 5 [/SUP], Luca Gelisio[SUP] 5 [/SUP], Martin Domaracky[SUP] 5 [/SUP], Philipp Middendorf[SUP] 5 [/SUP], Michael Groessler[SUP] 5 [/SUP], Fabian Trost[SUP] 5 [/SUP], Marina Galchenkova[SUP] 5 [/SUP], Aida Rahmani Mashhour[SUP] 5 [/SUP], Sofiane Saouane[SUP] 14 [/SUP], Johanna Hakanpää[SUP] 14 [/SUP], Markus Wolf[SUP] 15 [/SUP], Maria Garcia Alai[SUP] 13 [/SUP], Dusan Turk[SUP] 16 17 [/SUP], Arwen R Pearson[SUP] 3 18 [/SUP], Henry N Chapman[SUP] 3 5 19 [/SUP], Winfried Hinrichs[SUP] 20 [/SUP], Carsten Wrenger[SUP] 4 [/SUP], Alke Meents[SUP] 5 [/SUP], Christian Betzel[SUP] 21 22 [/SUP]
Affiliations
- PMID: 35953531
- DOI: 10.1038/s42003-022-03737-7
Abstract
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.