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Reinke, P.Y.A.* ; de Souza, E.E.* ; Gunther, S.* ; Falke, S.* ; Lieske, J.* ; Ewert, W.* ; Loboda, J.* ; Herrmann, A. ; Rahmani Mashhour, A.* ; Karničar, K.* ; Usenik, A.* ; Lindič, N.* ; Sekirnik, A.* ; Botosso, V.F.* ; Santelli, G.M.M.* ; Kapronezai, J.* ; de Araújo, M.V.* ; Silva-Pereira, T.T.* ; Filho, A.F.S.* ; Tavares, M.S.* ; Flórez-Álvarez, L.* ; de Oliveira, D.B.L.* ; Durigon, E.L.* ; Giaretta, P.R.* ; Heinemann, M.B.* ; Hauser, M.* ; Seychell, B.* ; Böhler, H.* ; Rut, W.* ; Drag, M.* ; Beck, T.* ; Cox, R.* ; Chapman, H.N.* ; Betzel, C.* ; Brehm, W.* ; Hinrichs, W.* ; Ebert, G. ; Latham, S.L.* ; Guimarães, A.M.S.* ; Turk, D.* ; Wrenger, C.* ; Meents, A.*

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

Comm. Biol. 6:1058 (2023)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
ISSN (print) / ISBN 2399-3642
e-ISSN 2399-3642
Zeitschrift Communications Biology
Quellenangaben Band: 6, Heft: 1, Seiten: , Artikelnummer: 1058 Supplement: ,
Verlag Springer
Verlagsort London
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Virology (VIRO)