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

<div class='caption-title'>Cell entry pathways of SARS-CoV-2.</div>
<div class='caption-title'>Inhibitor binding to the active site of CatL.</div>
<div class='caption-title'>Calpeptin and S-Calpeptin inhibit SARS-CoV-2 infection.</div>
Reinke PYA, de Souza EE, Günther S, Falke S, Lieske J, Ewert W, Loboda J, Herrmann A, Rahmani Mashhour A, Karničar K, Usenik A, Lindič N, Sekirnik A, Botosso VF, Santelli GMM, Kapronezai J, de Araújo MV, Silva-Pereira TT, Filho AFS, Tavares MS, Flórez-Álvarez L, de Oliveira DBL, Durigon EL, Giaretta PR, Heinemann MB, Hauser M, Seychell B, Böhler H, Rut W, Drag M, Beck T, Cox R, Chapman HN, Betzel C, Brehm W, Hinrichs W, Ebert G, Latham SL, Guimarães AMS, Turk D, Wrenger C, Meents A
OpenAccess logo Commun Biol 6 1058 (2023)
Related entries: 7qgw, 7qka, 7qkb, 7z3t, 7z3u, 7z58, 8c3d

Cited: 1 times
EuropePMC logo PMID: 37853179

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.

Articles - 7qkc mentioned but not cited (1)

  1. Calpeptin is a potent cathepsin inhibitor and drug candidate for SARS-CoV-2 infections. Reinke PYA, de Souza EE, Günther S, Falke S, Lieske J, Ewert W, Loboda J, Herrmann A, Rahmani Mashhour A, Karničar K, Usenik A, Lindič N, Sekirnik A, Botosso VF, Santelli GMM, Kapronezai J, de Araújo MV, Silva-Pereira TT, Filho AFS, Tavares MS, Flórez-Álvarez L, de Oliveira DBL, Durigon EL, Giaretta PR, Heinemann MB, Hauser M, Seychell B, Böhler H, Rut W, Drag M, Beck T, Cox R, Chapman HN, Betzel C, Brehm W, Hinrichs W, Ebert G, Latham SL, Guimarães AMS, Turk D, Wrenger C, Meents A. Commun Biol 6 1058 (2023)




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