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Cited by 485

The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.

Mechanism and inhibition of the papain‐like protease, PLpro, of SARS‐CoV‐2

Open access
Klemm, Theresa, Ebert, Gregor, Calleja, Dale J, Allison, Cody C, Richardson, Lachlan W, Bernardini, Jonathan P, Lu, Bernadine GC, Kuchel, Nathan W, Grohmann, Christoph, Shibata, Yuri, Gan, Zhong Yan, Cooney, James P, Doerflinger, Marcel, Au, Amanda E, Blackmore, Timothy R, van der Heden van Noort, Gerbrand J, Geurink, Paul P, Ovaa, Huib, Newman, Janet, Riboldi‐Tunnicliffe, Alan, Czabotar, Peter E, Mitchell, Jeffrey P, Feltham, Rebecca, Lechtenberg, Bernhard C, Lowes, Kym N, Dewson, Grant, Pellegrini, Marc, Lessene, Guillaume, Komander, David·2020·The EMBO Journal

Abstract

The SARS‐CoV‐2 coronavirus encodes an essential papain‐like protease domain as part of its non‐structural protein (nsp)‐3, namely SARS2 PLpro, that cleaves the viral polyprotein, but also removes ubiquitin‐like ISG15 protein modifications as well as, with lower activity, Lys48‐linked polyubiquitin. Structures of PLpro bound to ubiquitin and ISG15 reveal that the S1 ubiquitin‐binding site is responsible for high ISG15 activity, while the S2 binding site provides Lys48 chain specificity and cleavage efficiency. To identify PLpro inhibitors in a repurposing approach, screening of 3,727 unique approved drugs and clinical compounds against SARS2 PLpro identified no compounds that inhibited PLpro consistently or that could be validated in counterscreens. More promisingly, non‐covalent small molecule SARS PLpro inhibitors also target SARS2 PLpro, prevent self‐processing of nsp3 in cells and display high potency and excellent antiviral activity in a SARS‐CoV‐2 infection model.

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Metadata

Authors
Klemm, T., Ebert, G., Calleja, D. J., Allison, C. C., Richardson, L. W., Bernardini, J. P., Lu, B. G., Kuchel, N. W., Grohmann, C., Shibata, Y., Gan, Z. Y., Cooney, J. P., Doerflinger, M., Au, A. E., Blackmore, T. R., van der Heden van Noort, G. J., Geurink, P. P., Ovaa, H., Newman, J., Riboldi‐Tunnicliffe, A., Czabotar, P. E., Mitchell, J. P., Feltham, R., Lechtenberg, B. C., Lowes, K. N., Dewson, G., Pellegrini, M., Lessene, G., & Komander, D.
Venue
The EMBO Journal
Published
2020-08-26
Volume
39
Issue
18
Pages
e106275-e106275
ISSN
  • 0261-4189 (ISSN-L)
  • 1460-2075
OpenAlex
W3080855264
Cited by
485
References
8
FWCI
9.87
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Mechanism and inhibition of the papain‐like protease, PLpro, of SARS‐CoV‐2. https://app.cochat.ai/papers/10.15252/embj.2020106275
The paper
Klemm, T., Ebert, G., Calleja, D. J., Allison, C. C., Richardson, L. W., Bernardini, J. P., Lu, B. G., Kuchel, N. W., Grohmann, C., Shibata, Y., Gan, Z. Y., Cooney, J. P., Doerflinger, M., Au, A. E., Blackmore, T. R., van der Heden van Noort, G. J., Geurink, P. P., Ovaa, H., Newman, J., . . . Komander, D. (2020). Mechanism and inhibition of the papain‐like protease, PLpro, of SARS‐CoV‐2. The EMBO Journal. https://doi.org/10.15252/embj.2020106275

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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