Studies on the selectivity of the SARS-CoV-2 papain-like protease reveal the importance of the P2′ proline of the viral polyprotein

Author:

Chan H. T. Henry1ORCID,Brewitz Lennart1ORCID,Lukacik Petra23ORCID,Strain-Damerell Claire23ORCID,Walsh Martin A.23ORCID,Schofield Christopher J.1ORCID,Duarte Fernanda1ORCID

Affiliation:

1. Chemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK

2. Diamond Light Source Ltd., Harwell Science and Innovation Campus, Didcot, OX11 0DE, UK

3. Research Complex at Harwell, Harwell Science and Innovation Campus, Didcot, OX11 0FA, UK

Abstract

Computational modeling of how SARS-CoV-2 PLpro binds viral polyprotein-derived oligopeptide substrates reveals that a proline located at the P2′ position promotes catalysis, validated by residue substitutions and mass spectrometry-based analyses.

Funder

Biotechnology and Biological Sciences Research Council

Cancer Research UK

Engineering and Physical Sciences Research Council

Wellcome Trust

King Abdulaziz University

Publisher

Royal Society of Chemistry (RSC)

Subject

Biochemistry, Genetics and Molecular Biology (miscellaneous),Molecular Biology,Biochemistry,Chemistry (miscellaneous)

Reference85 articles.

1. SARS-CoV-2 proteases PLpro and 3CLpro cleave IRF3 and critical modulators of inflammatory pathways (NLRP12 and TAB1): implications for disease presentation across species

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3. Targeting SARS-CoV-2 Proteases for COVID-19 Antiviral Development

4. An oral SARS-CoV-2 M pro inhibitor clinical candidate for the treatment of COVID-19

5. US Food & Drug Administration, Coronavirus (COVID-19) Update: FDA Authorizes First Oral Antiviral for Treatment of COVID-19, https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-first-oral-antiviral-treatment-covid-19 , (accessed 2021-12-22)

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