TY  - JOUR
A1  - Doijen, Jordi
A1  - Temmerman, Koen
A1  - Eynde, Christel van der
A1  - Diels, Annick
A1  - Broeck, Nick van der
A1  - Gool, Michiel van
A1  - Heo, Inha
A1  - Jaensch, Steffen
A1  - Zwaagstra, Marleen
A1  - Diosa Toro, Mayra
A1  - Chiu, Winston
A1  - De Jonghe, Steven
A1  - Leyssen, Pieter
A1  - Bojkova, Denisa
A1  - Ciesek, Sandra
A1  - Cinatl, Jindrich
A1  - Verschueren, Lore
A1  - Buyck, Christophe
A1  - Kuppeveld, Franciscus Johannes Maria van
A1  - Neyts, Johan
A1  - Loock, Marnix van
A1  - Damme, Ellen van
T1  - Identification of Z-Tyr-Ala-CHN2, a cathepsin L inhibitor with broad-spectrum cell-specific activity against coronaviruses, including SARS-CoV-2
T2  - Microorganisms
N2  - The ongoing COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is partly under control by vaccination. However, highly potent and safe antiviral drugs for SARS-CoV-2 are still needed to avoid development of severe COVID-19. We report the discovery of a small molecule, Z-Tyr-Ala-CHN2, which was identified in a cell-based antiviral screen. The molecule exerts sub-micromolar antiviral activity against SARS-CoV-2, SARS-CoV-1, and human coronavirus 229E. Time-of-addition studies reveal that Z-Tyr-Ala-CHN2 acts at the early phase of the infection cycle, which is in line with the observation that the molecule inhibits cathepsin L. This results in antiviral activity against SARS-CoV-2 in VeroE6, A549-hACE2, and HeLa-hACE2 cells, but not in Caco-2 cells or primary human nasal epithelial cells since the latter two cell types also permit entry via transmembrane protease serine subtype 2 (TMPRSS2). Given their cell-specific activity, cathepsin L inhibitors still need to prove their value in the clinic; nevertheless, the activity profile of Z-Tyr-Ala-CHN2 makes it an interesting tool compound for studying the biology of coronavirus entry and replication.
KW  - cathepsin L inhibitor
KW  - coronavirus
KW  - in vitro
KW  - phenotypic screening;
KW  - SARS-CoV-2
Y1  - 2023
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/79545
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-795457
SN  - 2076-2607
VL  - 11
IS  - 3, art. 717
PB  - MDPI
CY  - Basel
ER  -