Journal Article

PUBDB-2022-04889

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Antiviral activity of natural phenolic compounds in complex at an allosteric site of SARS-CoV-2 papain-like protease

Srinivasan, V. (Corresponding author)Extern*EMBL* ; Brognaro, H.Extern*XFEL.EU*EMBL* ; Prabhu, P. R. ; de Souza, E. E. ; Guenther, S.CFEL*XFEL.EU*DESY* ; Reinke, P.CFEL*DESY* ; Lane, T.CFEL*DESY* ; Ginn, H.Extern*XFEL.EU* ; Han, H.XFEL.EU* ; Ewert, W.CFEL*DESY* ; Sprenger, J.CFEL*DESY* ; Koua, F. H. M.CFEL*XFEL.EU*DESY* ; Falke, S.CFEL*EMBL*DESY* ; Werner, N.EMBL* ; Andaleeb, H.Extern*XFEL.EU* ; Ullah, N.EMBL*DESY* ; Franca, B. A.XFEL.EU* ; Wang, M.CFEL*EMBL*DESY* ; Barra, A.Extern* ; Perbandt, M.Extern*XFEL.EU* ; Schwinzer, M.Extern*EMBL* ; Schmidt, C. ; Brings, L.XFEL.EU* ; Lorenzen, K.XFEL.EU* ; Schubert, R.XFEL.EU* ; Machado, R. R. G. ; Candido, E. D. ; Oliveira, D. B. L. ; Durigon, E. L. ; Niebling, S.CFEL*Extern*EMBL* ; Garcia, A. S. ; Yefanov, O.CFEL*XFEL.EU*DESY* ; Lieske, J.CFEL*XFEL.EU*DESY* ; Gelisio, L.CFEL*DESY* ; Domaracky, M.Extern*XFEL.EU* ; Middendorf, P.CFEL*DESY* ; Groessler, M.CFEL*DESY* ; Trost, F.CFEL*DESY* ; Galchenkova, M.CFEL*XFEL.EU*DESY* ; Mashhour, A. R.CFEL*DESY* ; Saouane, S.Extern*DESY* ; Hakanpää, J.DESY* ; Wolf, M.DESY* ; Alai, M. G. ; Turk, D.CFEL* ; Pearson, A.Extern*XFEL.EU*EMBL* ; Chapman, H. N.CFEL*XFEL.EU*DESY* ; Hinrichs, W.Extern* ; Wrenger, C.Extern* ; Meents, A.CFEL*XFEL.EU*DESY* ; Betzel, C. (Corresponding author)Extern*

2022
Springer Nature London

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Please use a persistent id in citations: doi:10.1038/s42003-022-03737-7  doi:10.3204/PUBDB-2022-04889

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.

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Contributing Institute(s):

1. FS-CFEL-1 Fachgruppe BMX (FS-CFEL-1-BMX)
2. CFEL-Coherent X-Ray Imaging (FS-CFEL-1)
3. FS-CFEL-1 Fachgruppe PBIO (FS-CFEL-1-PBIO)
4. Experimentebetreuung PETRA III (FS-PET-D)

Research Program(s):

1. 633 - Life Sciences – Building Blocks of Life: Structure and Function (POF4-633) (POF4-633)
2. 6G3 - PETRA III (DESY) (POF4-6G3) (POF4-6G3)
3. DFG project 390715994 - EXC 2056: CUI: Advanced Imaging of Matter (390715994) (390715994)
4. DFG project 194651731 - EXC 1074: Hamburger Zentrum für ultraschnelle Beobachtung (CUI): Struktur, Dynamik und Kontrolle von Materie auf atomarer Skala (194651731) (194651731)
5. HIDSS-0002 - DASHH: Data Science in Hamburg - Helmholtz Graduate School for the Structure of Matter (2019_IVF-HIDSS-0002) (2019_IVF-HIDSS-0002)

Experiment(s):

1. PETRA Beamline P11 (PETRA III)

Appears in the scientific report 2022

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