9BRV

SARS-CoV-2 Papain-like Protease (PLpro) with Fragment 5

This is a non-PDB format compatible entry.

Summary for 9BRV

• Entry DOI: 10.2210/pdb9brv/pdb
• Descriptor: Papain-like protease nsp3, N-[2-(dimethylamino)ethyl]-N'-(3-methylphenyl)thiourea, ZINC ION, ... (6 entities in total)
• Functional Keywords: plpro, sars-cov-2, drug discovery, inhibitor, viral protein, hydrolase
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2)
• Total number of polymer chains: 2
• Total formula weight: 73482.88

Authors

Amporndanai, K.,Zhao, B.,Fesik, S.W. (deposition date: 2024-05-11, release date: 2024-07-31, Last modification date: 2024-09-04)

Primary citation

Taylor, A.J.,Amporndanai, K.,Rietz, T.A.,Zhao, B.,Thiruvaipati, A.,Wei, Q.,South, T.M.,Crow, M.M.,Apakama, C.,Sensintaffar, J.L.,Phan, J.,Lee, T.,Fesik, S.W.
Fragment-Based Screen of SARS-CoV-2 Papain-like Protease (PL pro ).
Acs Med.Chem.Lett., 15:1351-1357, 2024

PubMed Abstract: Coronaviruses have been responsible for numerous viral outbreaks in the past two decades due to the high transmission rate of this family of viruses. The deadliest outbreak is the recent Covid-19 pandemic, which resulted in over 7 million deaths worldwide. SARS-CoV-2 papain-like protease (PL) plays a key role in both viral replication and host immune suppression and is highly conserved across the coronavirus family, making it an ideal drug target. Herein we describe a fragment-based screen against PL using protein-observed NMR experiments, identifying 77 hit fragments. Analyses of NMR perturbation patterns and X-ray cocrystallized structures reveal fragments bind to two distinct regions of the protein. Importantly none of the fragments identified belong to the same chemical class as the few reported inhibitors, allowing for the discovery of a novel class of PL inhibitors.

PubMed: 39140055
DOI: 10.1021/acsmedchemlett.4c00238

Experimental method

X-RAY DIFFRACTION (2.6 Å)