8C3D

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

これはPDB形式変換不可エントリーです。

8C3D の概要

• エントリーDOI: 10.2210/pdb8c3d/pdb
• 関連するBIRD辞書のPRD_ID: PRD_002387
• 分子名称: Cathepsin K, 3-PYRIDIN-4-YL-2,4-DIHYDRO-INDENO[1,2-.C.]PYRAZOLE, CALCIUM ION, ... (4 entities in total)
• 機能のキーワード: cathepsin, inhibitor, hydrolase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 23926.02

構造登録者

Loboda, J.,Karnicar, K.,Lindic, N.,Usenik, A.,Lieske, J.,Meents, A.,Guenther, S.,Reinke, P.Y.A.,Falke, S.,Ewert, W.,Turk, D. (登録日: 2022-12-23, 公開日: 2023-09-27, 最終更新日: 2023-11-15)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2 Å)