Zinc pyrithione is a potent inhibitor of PL Pro and cathepsin L enzymes with ex vivo inhibition of SARS-CoV-2 entry and replication
Kladnik, Jerneja (Univerza V Ljubljani)
Dolinar, Ana (Univerza V Ljubljani)
Kljun, Jakob (Univerza V Ljubljani)
Perea, David (Vall d'Hebron Institut de Recerca (VHIR))
Grau Expósito, Judith (Vall d'Hebron Institut de Recerca (VHIR))
Genescà Ferrer, Meritxell (Vall d'Hebron Institut de Recerca (VHIR))
Novinec, Marko (Univerza V Ljubljani)
Buzón, Maria José (Vall d'Hebron Institut de Recerca (VHIR))
Turel, Iztok (Univerza V Ljubljani)
Universitat Autònoma de Barcelona

Date:	2022
Abstract:	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 (IC=1. 88 ± 0. 49 µM) and PL Pro (IC=0. 50 ± 0. 07 µM), 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.
Grants:	Instituto de Salud Carlos III CP17/00179 Fundació la Marató de TV3 202112FMTV3 Fundació la Marató de TV3 202104FMTV3
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Antiviral agents ; SARS-CoV-2 ; Inhibition ; Pyrithione ; Zinc
Published in:	Journal of Enzyme Inhibition and Medicinal Chemistry, Vol. 37 (august 2022) , p. 2158-2168, ISSN 1475-6374

DOI: 10.1080/14756366.2022.2108417
PMID: 35943189

11 p, 1.7 MB

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