7z58

Crystal structure of human Cathepsin L in complex with covalently bound Calpeptin

spinqualitylabelsall models 7z58, resolution 1.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7z58 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.35Å Ligands: DMS, EDO, PEG, PGE, RN2 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CATL1_HUMAN Important for the overall degradation of proteins in lysosomes. Publication Abstract from PubMed Several drug screening campaigns identified Calpeptin as a drug candidate against SARS-CoV-2. Initially reported to target the viral main protease (M(pro)), its moderate activity in M(pro) inhibition assays hints at a second target. Indeed, we show that Calpeptin is an extremely potent cysteine cathepsin inhibitor, a finding additionally supported by X-ray crystallography. Cell infection assays proved Calpeptin's efficacy against SARS-CoV-2. Treatment of SARS-CoV-2-infected Golden Syrian hamsters with sulfonated Calpeptin at a dose of 1 mg/kg body weight reduces the viral load in the trachea. Despite a higher risk of side effects, an intrinsic advantage in targeting host proteins is their mutational stability in contrast to highly mutable viral targets. Here we show that the inhibition of cathepsins, a protein family of the host organism, by calpeptin is a promising approach for the treatment of SARS-CoV-2 and potentially other viral infections. Calpeptin is a potent cathepsin inhibitor and drug candidate for SARS-CoV-2 infections.,Reinke PYA, de Souza EE, Gunther S, Falke S, Lieske J, Ewert W, Loboda J, Herrmann A, Rahmani Mashhour A, Karnicar K, Usenik A, Lindic N, Sekirnik A, Botosso VF, Santelli GMM, Kapronezai J, de Araujo MV, Silva-Pereira TT, Filho AFS, Tavares MS, Florez-Alvarez L, de Oliveira DBL, Durigon EL, Giaretta PR, Heinemann MB, Hauser M, Seychell B, Bohler H, Rut W, Drag M, Beck T, Cox R, Chapman HN, Betzel C, Brehm W, Hinrichs W, Ebert G, Latham SL, Guimaraes AMS, Turk D, Wrenger C, Meents A Commun Biol. 2023 Oct 18;6(1):1058. doi: 10.1038/s42003-023-05317-9. PMID:37853179 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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