6mo1 | pdb_00006mo1

Structure of dengue virus protease with an allosteric Inhibitor that blocks replication

spinqualitylabelsall models 6mo1, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6mo1 is a 2 chain structure with sequence from Dengue virus 2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: I16 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Flaviviruses, including dengue, West Nile and recently emerged Zika virus, are important human pathogens, but there are no drugs to prevent or treat these viral infections. The highly conserved Flavivirus NS2B-NS3 protease is essential for viral replication and therefore a drug target. Compound screening followed by medicinal chemistry yielded a series of drug-like, broadly active inhibitors of Flavivirus proteases with IC50 as low as 120 nM. The inhibitor exhibited significant antiviral activities in cells (EC68: 300-600 nM) and in a mouse model of Zika virus infection. X-ray studies reveal that the inhibitors bind to an allosteric, mostly hydrophobic pocket of dengue NS3 and hold the protease in an open, catalytically inactive conformation. The inhibitors and their binding structures would be useful for rational drug development targeting Zika, dengue and other Flaviviruses. Discovery, X-ray Crystallography and Antiviral Activity of Allosteric Inhibitors of Flavivirus NS2B-NS3 Protease.,Yao Y, Huo T, Lin YL, Nie S, Wu F, Hua Y, Wu J, Kneubehl AR, Vogt MB, Rico-Hesse R, Song Y J Am Chem Soc. 2019 May 1;141(17):6832-6836. doi: 10.1021/jacs.9b02505. Epub 2019, Apr 23. PMID:31017399 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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