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Zinc pyrithione is a potent inhibitor of PLPro and cathepsin L enzymes with ex vivo inhibition of SARS-CoV-2 entry and replication
Kladnik et al., Journal of Enzyme Inhibition and Medicinal Chemistry, doi:10.1080/14756366.2022.2108417 (Ex Vivo)
Kladnik et al., Zinc pyrithione is a potent inhibitor of PLPro and cathepsin L enzymes with ex vivo inhibition of SARS-CoV-2.., Journal of Enzyme Inhibition and Medicinal Chemistry, doi:10.1080/14756366.2022.2108417 (Ex Vivo)
Aug 2022   Source   PDF  
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Ex Vivo study showing zinc pyrithione to be a potent inhibitor of SARS-CoV-2 entry and replication.
Kladnik et al., 9 Aug 2022, peer-reviewed, 9 authors.
Ex Vivo studies are an important part of preclinical research, however results may be very different in vivo.
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Abstract: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY 2022, VOL. 37, NO. 1, 2158–2168 https://doi.org/10.1080/14756366.2022.2108417 RESEARCH PAPER Zinc pyrithione is a potent inhibitor of PLPro and cathepsin L enzymes with ex vivo inhibition of SARS-CoV-2 entry and replication sitob, Meritxell Genescab, Marko Jerneja Kladnika, Ana Dolinara, Jakob Kljuna, David Pereab, Judith Grau-Expo a b a Novinec , Maria J. Buzon and Iztok Turel a Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia; bInfectious Diseases Department, Vall d’Hebron Research Institute (VHIR), Hospital Universitari Vall d’Hebron, Universitat Autonoma de Barcelona, VHIR Task Force COVID-19, Barcelona, Spain ABSTRACT ARTICLE HISTORY Zinc pyrithione (1a), together with its analogues 1b–h and ruthenium pyrithione complex 2a, were synthesised and evaluated for the stability in biologically relevant media and anti-SARS-CoV-2 activity. Zinc pyrithione revealed potent in vitro inhibition of cathepsin L (IC50¼1.88 ± 0.49 mM) and PLPro (IC50¼0.50 ± 0.07 mM), enzymes involved in SARS-CoV-2 entry and replication, respectively, as well as antiviral entry and replication properties in an ex vivo system derived from primary human lung tissue. Zinc complexes 1b–h expressed comparable in vitro inhibition. On the contrary, ruthenium complex 2a and the ligand pyrithione a itself expressed poor inhibition in mentioned assays, indicating the importance of the selection of metal core and structure of metal complex for antiviral activity. Safe, effective, and preferably oral at-home therapeutics for COVID-19 are needed and as such zinc pyrithione, which is also commercially available, could be considered as a potential therapeutic agent against SARS-CoV-2. Received 21 June 2022 Revised 23 July 2022 Accepted 27 July 2022
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