9puy | pdb_00009puy

SARS-CoV-2 Papain-like Protease (PLpro) in complex with Fragment 27

spinqualitylabelsall models 9puy, resolution 1.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9puy is a 4 chain structure with sequence from Severe acute respiratory syndrome coronavirus 2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.75Å Ligands: A1CLD, K, PO4, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed SARS-CoV-2 papain-like protease (PL(Pro)) plays a key role in viral replication and the host immune response and is a promising target for developing new antiviral treatments. We previously reported a fragment-based screen to identify hits that bind to SARS-CoV-2 PL(Pro). Here, we describe the discovery of potent PL(Pro) inhibitors by optimizing one of these hits via extensive medicinal chemistry guided by multiple X-ray structures of cocomplexes. Lead compound 46 is shown to bind to the S3 and S4 pockets with nanomolar affinity (0.4 muM) and exhibits robust cellular activity and resistance to mutation. This novel class of PL(Pro) inhibitors can potentially be used as a starting point for the development of inhibitors to combat the emergence of drug-resistant viral strains and future coronavirus outbreaks. Discovery of Fragment-Based Inhibitors of SARS-CoV-2 PL(Pro).,Wei Q, Taylor AJ, Barmade MA, Teuscher KB, Chowdhury S, Apakama C, Anderson-Daniels J, Yongqing Z, Schultz DC, Rietz TA, South TM, Crow MM, Zhao B, Amporndanai K, Sensintaffar JL, Phan J, Cherry S, Denison M, Lee T, Fesik SW J Med Chem. 2026 Jan 22;69(2):1419-1433. doi: 10.1021/acs.jmedchem.5c02832. Epub , 2026 Jan 11. PMID:41521555 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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