Details

Autor(en) / Beteiligte

• Osipiuk, Jerzy
• Azizi, Saara-Anne
• Dvorkin, Steve
• Endres, Michael
• Jedrzejczak, Robert
• Jones, Krysten A.
• Kang, Soowon
• Kathayat, Rahul S.
• Kim, Youngchang
• Lisnyak, Vladislav G.
• Maki, Samantha L.
• Nicolaescu, Vlad
• Taylor, Cooper A.
• Tesar, Christine
• Zhang, Yu-An
• Zhou, Zhiyao
• Randall, Glenn
• Michalska, Karolina
• Snyder, Scott A.
• Dickinson, Bryan C.
• Joachimiak, Andrzej

Titel

Structure of papain-like protease from SARS-CoV-2 and its complexes with non-covalent inhibitors

Ist Teil von

• Nature communications, 2021-02, Vol.12 (1), p.743-9, Article 743

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• The pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to expand. Papain-like protease (PLpro) is one of two SARS-CoV-2 proteases potentially targetable with antivirals. PLpro is an attractive target because it plays an essential role in cleavage and maturation of viral polyproteins, assembly of the replicase-transcriptase complex, and disruption of host responses. We report a substantive body of structural, biochemical, and virus replication studies that identify several inhibitors of the SARS-CoV-2 enzyme. We determined the high resolution structure of wild-type PLpro, the active site C111S mutant, and their complexes with inhibitors. This collection of structures details inhibitors recognition and interactions providing fundamental molecular and mechanistic insight into PLpro. All compounds inhibit the peptidase activity of PLpro in vitro, some block SARS-CoV-2 replication in cell culture assays. These findings will accelerate structure-based drug design efforts targeting PLpro to identify high-affinity inhibitors of clinical value. The SARS-CoV-2 papain-like protease (PLpro) is of interest as an antiviral drug target. Here, the authors synthesize and characterise naphthalene-based inhibitors for PLpro and present the crystal structures of PLpro in its apo state and with the bound inhibitors, which is of interest for further structure-based drug design efforts.