Crystal structure of SARS-CoV-2 papain-like protease.
Antiviral drug
Crystal structure
Drug design
PLpro
Proteinase inhibitor
SARS-CoV-2
Journal
Acta pharmaceutica Sinica. B
ISSN: 2211-3835
Titre abrégé: Acta Pharm Sin B
Pays: Netherlands
ID NLM: 101600560
Informations de publication
Date de publication:
Jan 2021
Jan 2021
Historique:
received:
31
07
2020
revised:
20
08
2020
accepted:
24
08
2020
pubmed:
9
9
2020
medline:
9
9
2020
entrez:
8
9
2020
Statut:
ppublish
Résumé
The pandemic of coronavirus disease 2019 (COVID-19) is changing the world like never before. This crisis is unlikely contained in the absence of effective therapeutics or vaccine. The papain-like protease (PLpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays essential roles in virus replication and immune evasion, presenting a charming drug target. Given the PLpro proteases of SARS-CoV-2 and SARS-CoV share significant homology, inhibitor developed for SARS-CoV PLpro is a promising starting point of therapeutic development. In this study, we sought to provide structural frameworks for PLpro inhibitor design. We determined the unliganded structure of SARS-CoV-2 PLpro mutant C111S, which shares many structural features of SARS-CoV PLpro. This crystal form has unique packing, high solvent content and reasonable resolution 2.5 Å, hence provides a good possibility for fragment-based screening using crystallographic approach. We characterized the protease activity of PLpro in cleaving synthetic peptide harboring nsp2/nsp3 juncture. We demonstrate that a potent SARS-CoV PLpro inhibitor GRL0617 is highly effective in inhibiting protease activity of SARS-CoV-2 with the IC
Identifiants
pubmed: 32895623
doi: 10.1016/j.apsb.2020.08.014
pii: S2211-3835(20)30698-5
pmc: PMC7467110
doi:
Types de publication
Journal Article
Langues
eng
Pagination
237-245Informations de copyright
© 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
Déclaration de conflit d'intérêts
The authors declare no conflicts of interest.
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