7Z3U

Crystal structure of SARS-CoV-2 Main Protease after incubation with Sulfo-Calpeptin

7Z3U の概要

• エントリーDOI: 10.2210/pdb7z3u/pdb
• 関連するPDBエントリー: 7QKA 7QKB 7QKC 7Z2K 7Z3T 7Z58
• 関連するBIRD辞書のPRD_ID: PRD_002387
• 分子名称: 3C-like proteinase nsp5, Calpetin, DIMETHYL SULFOXIDE, ... (6 entities in total)
• 機能のキーワード: main protease, mpro, cystein protease, drug development, drug target, peptide-like inhibitor, sars-cov-2, covid-19, hydrolase
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 68823.31

構造登録者

Reinke, P.Y.A.,Falke, S.,Lieske, J.,Ewert, W.,Loboda, J.,Rahmani Mashhour, A.,Hauser, M.,Karnicar, K.,Usenik, A.,Lindic, N.,Lach, M.,Boehler, H.,Beck, T.,Cox, R.,Chapman, H.N.,Hinrichs, W.,Turk, D.,Guenther, S.,Meents, A. (登録日: 2022-03-02, 公開日: 2023-03-22, 最終更新日: 2024-07-10)

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 (1.72 Å)