학술논문
Calpeptin is a potent cathepsin inhibitor and drug candidate for SARS-CoV-2 infections
Document Type
Original Paper
Author
Reinke, Patrick Y. A.; de Souza, Edmarcia Elisa; Günther, Sebastian; Falke, Sven; Lieske, Julia; Ewert, Wiebke; Loboda, Jure; Herrmann, Alexander; Rahmani Mashhour, Aida; Karničar, Katarina; Usenik, Aleksandra; Lindič, Nataša; Sekirnik, Andreja; Botosso, Viviane Fongaro; Santelli, Gláucia Maria Machado; Kapronezai, Josana; de Araújo, Marcelo Valdemir; Silva-Pereira, Taiana Tainá; Filho, Antônio Francisco de Souza; Tavares, Mariana Silva; Flórez-Álvarez, Lizdany; de Oliveira, Danielle Bruna Leal; Durigon, Edison Luiz; Giaretta, Paula Roberta; Heinemann, Marcos Bryan; Hauser, Maurice; Seychell, Brandon; Böhler, Hendrik; Rut, Wioletta; Drag, Marcin; Beck, Tobias; Cox, Russell; Chapman, Henry N.; Betzel, Christian; Brehm, Wolfgang; Hinrichs, Winfried; Ebert, Gregor; Latham, Sharissa L.; Guimarães, Ana Marcia de Sá; Turk, Dusan; Wrenger, Carsten; Meents, Alke
Source
Communications Biology. 6(1)
Subject
Language
English
ISSN
2399-3642
Abstract
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 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.
Reinke et. al. show that targeting host proteins like cathepsins is a promising strategy for treating SARS-CoV-2 and other viral infections due to their mutational stability in contrast to highly mutable viral targets.
Reinke et. al. show that targeting host proteins like cathepsins is a promising strategy for treating SARS-CoV-2 and other viral infections due to their mutational stability in contrast to highly mutable viral targets.