7QGW

Sulfonated Calpeptin is a promising drug candidate against SARS-CoV-2 infections

Summary for 7QGW

• Entry DOI: 10.2210/pdb7qgw/pdb
• Related PRD ID: PRD_002386
• Descriptor: Cathepsin L2, CHLORIDE ION, (4S)-2-METHYL-2,4-PENTANEDIOL, ... (6 entities in total)
• Functional Keywords: cathepsin, inhibitor, hydrolase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 50193.11

Authors

Loboda, J.,Karnicar, K.,Lindic, N.,Usenik, A.,Lieske, J.,Meents, A.,Guenther, S.,Reinke, P.Y.A.,Falke, S.,Ewert, W.,Turk, D. (deposition date: 2021-12-10, release date: 2022-12-21, Last modification date: 2024-10-23)

Primary citation

Reinke, P.Y.A.,de Souza, E.E.,Gunther, S.,Falke, S.,Lieske, J.,Ewert, W.,Loboda, J.,Herrmann, A.,Rahmani Mashhour, A.,Karnicar, K.,Usenik, A.,Lindic, N.,Sekirnik, A.,Botosso, V.F.,Santelli, G.M.M.,Kapronezai, J.,de Araujo, M.V.,Silva-Pereira, T.T.,Filho, A.F.S.,Tavares, M.S.,Florez-Alvarez, L.,de Oliveira, D.B.L.,Durigon, E.L.,Giaretta, P.R.,Heinemann, M.B.,Hauser, M.,Seychell, B.,Bohler, H.,Rut, W.,Drag, M.,Beck, T.,Cox, R.,Chapman, H.N.,Betzel, C.,Brehm, W.,Hinrichs, W.,Ebert, G.,Latham, S.L.,Guimaraes, A.M.S.,Turk, D.,Wrenger, C.,Meents, A.
Calpeptin is a potent cathepsin inhibitor and drug candidate for SARS-CoV-2 infections.
Commun Biol, 6:1058-1058, 2023

PubMed Abstract: Several drug screening campaigns identified Calpeptin as a drug candidate against SARS-CoV-2. Initially reported to target the viral main protease (M), its moderate activity in M 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.

PubMed: 37853179
DOI: 10.1038/s42003-023-05317-9

Experimental method

X-RAY DIFFRACTION (1.3 Å)