Calpeptin is a potent cathepsin inhibitor and drug candidate for SARS-CoV-2 infections. Academic Article uri icon

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 1mg/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.

published proceedings

  • Commun Biol

author list (cited authors)

  • Reinke, P., de Souza, E. E., Gnther, S., Falke, S., Lieske, J., Ewert, W., ... Meents, A.

complete list of authors

  • Reinke, Patrick YA||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

publication date

  • October 2023