Biochemical characterization of protease activity of Nsp3 from SARS-CoV-2 and its inhibition by nanobodies

Lee A. Armstrong; Sven M. Lange; Virginia Dee Cesare; Stephen P. Matthews; Raja Sekhar Nirujogi; Isobel Cole; Anthony Hope; Fraser Cunningham; Rachel Toth; Rukmini Mukherjee; Denisa Bojkova; Franz Gruber; David Gray; Paul G. Wyatt; Jindrich Cinatl; Ivan Dikic; Paul Davies; Yogesh Kulathu

doi:10.1371/journal.pone.0253364

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Open Access

Peer-reviewed

Research Article

Biochemical characterization of protease activity of Nsp3 from SARS-CoV-2 and its inhibition by nanobodies

Lee A. Armstrong ,

Contributed equally to this work with: Lee A. Armstrong, Sven M. Lange

Roles Conceptualization, Investigation, Writing – review & editing

Affiliation MRC Protein Phosphorylation and Ubiquitylation Unit, Sir James Black Centre, School of Life Sciences, University of Dundee, Dundee, Scotland, United Kingdom

https://orcid.org/0000-0001-7036-625X

⨯
Sven M. Lange ,

Contributed equally to this work with: Lee A. Armstrong, Sven M. Lange

Roles Conceptualization, Investigation, Methodology, Writing – review & editing

Affiliation MRC Protein Phosphorylation and Ubiquitylation Unit, Sir James Black Centre, School of Life Sciences, University of Dundee, Dundee, Scotland, United Kingdom

https://orcid.org/0000-0002-6011-8647

⨯
Virginia Dee Cesare,

Roles Formal analysis, Investigation, Writing – review & editing

Affiliation MRC Protein Phosphorylation and Ubiquitylation Unit, Sir James Black Centre, School of Life Sciences, University of Dundee, Dundee, Scotland, United Kingdom

https://orcid.org/0000-0002-2640-6389

⨯
Stephen P. Matthews,

Roles Conceptualization, Formal analysis, Investigation

Affiliation MRC Protein Phosphorylation and Ubiquitylation Unit, Sir James Black Centre, School of Life Sciences, University of Dundee, Dundee, Scotland, United Kingdom
⨯
Raja Sekhar Nirujogi,

Roles Formal analysis, Investigation, Writing – review & editing

Affiliation MRC Protein Phosphorylation and Ubiquitylation Unit, Sir James Black Centre, School of Life Sciences, University of Dundee, Dundee, Scotland, United Kingdom
⨯
Isobel Cole,

Roles Investigation

Affiliation MRC Protein Phosphorylation and Ubiquitylation Unit, Sir James Black Centre, School of Life Sciences, University of Dundee, Dundee, Scotland, United Kingdom
⨯
Anthony Hope †,

† Deceased.

Roles Formal analysis

Affiliation Drug Discovery Unit, School of Life Sciences, University of Dundee, Dundee, Scotland, United Kingdom
⨯
Fraser Cunningham,

Roles Formal analysis, Writing – review & editing

Affiliation Drug Discovery Unit, School of Life Sciences, University of Dundee, Dundee, Scotland, United Kingdom
⨯
Rachel Toth,

Roles Investigation, Resources

Affiliation MRC Reagents and Services, University of Dundee, Dundee, Scotland, United Kingdom
⨯
Rukmini Mukherjee,

Roles Investigation

Affiliations Institute of Biochemistry II, Goethe University Frankfurt Medical Faculty, University Hospital, Frankfurt am Main, Germany, Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt, Frankfurt am Main, Germany
⨯
Denisa Bojkova,

Roles Investigation

Affiliation Institute of Medical Virology, University Hospital Frankfurt, Frankfurt am Main, Germany
⨯
Franz Gruber,

Roles Resources

Affiliation National Phenotypic Screening Centre, University of Dundee, Dundee, Scotland, United Kingdom
⨯
David Gray,

Roles Funding acquisition, Supervision, Writing – review & editing

Affiliation Drug Discovery Unit, School of Life Sciences, University of Dundee, Dundee, Scotland, United Kingdom

https://orcid.org/0000-0001-9512-3828

⨯
Paul G. Wyatt,

Roles Writing – review & editing

Affiliation Drug Discovery Unit, School of Life Sciences, University of Dundee, Dundee, Scotland, United Kingdom
⨯
Jindrich Cinatl,

Roles Supervision

Affiliation Institute of Medical Virology, University Hospital Frankfurt, Frankfurt am Main, Germany
⨯
Ivan Dikic,

Roles Funding acquisition, Supervision, Writing – review & editing

Affiliations Institute of Biochemistry II, Goethe University Frankfurt Medical Faculty, University Hospital, Frankfurt am Main, Germany, Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt, Frankfurt am Main, Germany, Max Planck Institute of Biophysics, Frankfurt am Main, Germany
⨯
Paul Davies,

Roles Project administration, Writing – review & editing

Affiliation MRC Protein Phosphorylation and Ubiquitylation Unit, Sir James Black Centre, School of Life Sciences, University of Dundee, Dundee, Scotland, United Kingdom
⨯
[ ... ],
Yogesh Kulathu

Roles Conceptualization, Formal analysis, Funding acquisition, Supervision, Writing – original draft, Writing – review & editing

* E-mail: y.kulathu@dundee.ac.uk

Affiliation MRC Protein Phosphorylation and Ubiquitylation Unit, Sir James Black Centre, School of Life Sciences, University of Dundee, Dundee, Scotland, United Kingdom

https://orcid.org/0000-0002-3274-1642

⨯
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Biochemical characterization of protease activity of Nsp3 from SARS-CoV-2 and its inhibition by nanobodies

Lee A. Armstrong,
Sven M. Lange,
Virginia Dee Cesare,
Stephen P. Matthews,
Raja Sekhar Nirujogi,
Isobel Cole,
Anthony Hope,
Fraser Cunningham,
Rachel Toth,
Rukmini Mukherjee

Published: July 16, 2021
https://doi.org/10.1371/journal.pone.0253364

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