7OFS

Structure of SARS-CoV-2 Papain-like protease PLpro in complex with 4-(2-hydroxyethyl)phenol

Summary for 7OFS

• Entry DOI: 10.2210/pdb7ofs/pdb
• Related: 7NFV 7OFT 7OFU
• Descriptor: Papain-like protease nsp3, ZINC ION, CHLORIDE ION, ... (7 entities in total)
• Functional Keywords: papain-like protease sars-cov-2 hydrolase zinc binding protein, hydrolase
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2)
• Total number of polymer chains: 1
• Total formula weight: 36168.50

Authors

Srinivasan, V.,Werner, N.,Falke, S.,Guenther, S.,Reinke, P.,Ewert, W.,Sprenger, J.,Koua, F.,Brognaro, H.,Ullah, N.,Andaleeb, H.,Perbandt, M.,Alves Franca, B.,Schwinzer, M.,Wang, M.,Lieske, J.,Ginn, H.,Lane, T.J.,Yefanov, O.,Gelisio, L.,Hakanpaeae, J.,Saouane, S.,Tolstikova, A.,Groessler, M.,Fleckenstein, H.,Trost, F.,Wolf, M.,Lorenzen, K.,Schubert, R.,Han, H.,Schmidt, C.,Brings, L.,Galchenkova, M.,Gevorkov, Y.,Li, C.,Perk, A.,Awel, S.,Wahab, A.,Choudary, I.,Turk, D.,Hinrichs, W.,Chapman, H.N.,Meents, A.,Betzel, C. (deposition date: 2021-05-05, release date: 2021-05-12, Last modification date: 2024-01-31)

Primary citation

Srinivasan, V.,Brognaro, H.,Prabhu, P.R.,de Souza, E.E.,Gunther, S.,Reinke, P.Y.A.,Lane, T.J.,Ginn, H.,Han, H.,Ewert, W.,Sprenger, J.,Koua, F.H.M.,Falke, S.,Werner, N.,Andaleeb, H.,Ullah, N.,Franca, B.A.,Wang, M.,Barra, A.L.C.,Perbandt, M.,Schwinzer, M.,Schmidt, C.,Brings, L.,Lorenzen, K.,Schubert, R.,Machado, R.R.G.,Candido, E.D.,Oliveira, D.B.L.,Durigon, E.L.,Niebling, S.,Garcia, A.S.,Yefanov, O.,Lieske, J.,Gelisio, L.,Domaracky, M.,Middendorf, P.,Groessler, M.,Trost, F.,Galchenkova, M.,Mashhour, A.R.,Saouane, S.,Hakanpaa, J.,Wolf, M.,Alai, M.G.,Turk, D.,Pearson, A.R.,Chapman, H.N.,Hinrichs, W.,Wrenger, C.,Meents, A.,Betzel, C.
Antiviral activity of natural phenolic compounds in complex at an allosteric site of SARS-CoV-2 papain-like protease.
Commun Biol, 5:805-805, 2022

PubMed 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.

PubMed: 35953531
DOI: 10.1038/s42003-022-03737-7

Experimental method

X-RAY DIFFRACTION (1.9 Å)