{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Falke S"],"funding":["Helmholtz-Gemeinschaft","Deutsche Forschungsgemeinschaft","Helmholtz Association","Javna Agencija za Raziskovalno Dejavnost RS","European Commission","Bundesministerium für Bildung und Forschung"],"pagination":["7048-7067"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11089505"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["67(9)"],"pubmed_abstract":["Emerging RNA viruses, including SARS-CoV-2, continue to be a major threat. Cell entry of SARS-CoV-2 particles via the endosomal pathway involves cysteine cathepsins. Due to ubiquitous expression, cathepsin L (CatL) is considered a promising drug target in the context of different viral and lysosome-related diseases. We characterized the anti-SARS-CoV-2 activity of a set of carbonyl- and succinyl epoxide-based inhibitors, which were previously identified as inhibitors of cathepsins or related cysteine proteases. Calpain inhibitor XII, MG-101, and CatL inhibitor IV possess antiviral activity in the very low nanomolar EC<sub>50</sub> range in Vero E6 cells and inhibit CatL in the picomolar <i>K<sub>i</sub></i> range. We show a relevant off-target effect of CatL inhibition by the coronavirus m"],"journal":["Journal of medicinal chemistry"],"pubmed_title":["Structural Elucidation and Antiviral Activity of Covalent Cathepsin L Inhibitors."],"pmcid":["PMC11089505"],"funding_grant_id":["P1-0048","SFragX","FISCOV","InternLabs-0011-HIR3X","16GW0277","KA1-Co-06 â??CORAEROâ?&#157;","EFRE-REACT","SFB-TRR353 (project 471011418)","031B0405D","IO-0048"],"pubmed_authors":["Falke S","Usenik A","Turk D","Loboda J","Dretnik K","Lieske J","Herrmann A","Sekirnik A","Meents A","Turk V","Reinke PYA","Ewert W","Hinrichs W","Lindic N","Tsuge H","Gunther S","Karnicar K","Chapman HN","Ebert G"],"additional_accession":[]},"is_claimable":false,"name":"Structural Elucidation and Antiviral Activity of Covalent Cathepsin L Inhibitors.","description":"Emerging RNA viruses, including SARS-CoV-2, continue to be a major threat. Cell entry of SARS-CoV-2 particles via the endosomal pathway involves cysteine cathepsins. Due to ubiquitous expression, cathepsin L (CatL) is considered a promising drug target in the context of different viral and lysosome-related diseases. We characterized the anti-SARS-CoV-2 activity of a set of carbonyl- and succinyl epoxide-based inhibitors, which were previously identified as inhibitors of cathepsins or related cysteine proteases. Calpain inhibitor XII, MG-101, and CatL inhibitor IV possess antiviral activity in the very low nanomolar EC<sub>50</sub> range in Vero E6 cells and inhibit CatL in the picomolar <i>K<sub>i</sub></i> range. We show a relevant off-target effect of CatL inhibition by the coronavirus m","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 May","modification":"2026-04-08T19:50:52.032Z","creation":"2026-04-08T14:33:23.408Z"},"accession":"S-EPMC11089505","cross_references":{"pubmed":["38630165"],"doi":["10.1021/acs.jmedchem.3c02351"]}}