| Autor: |
Patrick Reinke, Edmarcia de Souza, Sebastian Günther, Sven Falke, Julia Lieske, Wiebke Ewert, Jure Loboda, Alexander Herrmann, Aida Rahmani Mashhour, Katarina Karnicar, Aleksandra Usenik, Natasa Lindic, Andreja Sekirnik, Viviane Botosso, Gláucia Machado Santelli, Josana Kapronezai, Marcelo de Araújo, Taiana Silva-Pereira, Antonio Souza Filho, Mariana Tavares, Lizdany Flórez-Álvarez, Danielle Oliveira, Edison Durigon, Paula Giaretta, Marcos Heinemann, Maurice Hauser, Brandon Seychell, Hendrik Böhler, Wioletta Rut, Marcin Drag, Tobias Beck, Russell Cox, Henry Chapman, Christian Betzel, Wolfgang Brehm, Winfried Hinrichs, Gregor Ebert, Sharissa Latham, Ana Marcia Guimarães, Dušan Turk, Carsten Wrenger, Alke Meents |
| Rok vydání: |
2023 |
| Popis: |
Several drug screening campaigns identified Calpeptin as a drug candidate against SARS-CoV-2. Initially reported to target the viral main protease (Mpro), its moderate activity in Mpro 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 significantly reduces the viral load in the trachea. Our results show that the inhibition of cathepsins, a protein family of the host organism, is a promising approach for the treatment of SARS-CoV-2 and potentially other viral infections. An intrinsic advantage in targeting host proteins is their mutational stability in contrast to highly mutable viral targets. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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