20.500.12556/RUL-145390 Zinc pyrithione is a potent inhibitor of PL$^{Pro}$ and cathepsin L enzymes with ex vivo inhibition of SARS-CoV-2 entry and replication 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$_{50}$=1.88 ± 0.49 µM) and PL$^{Pro}$ (IC$_{50}$=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. antiviral agents SARS-CoV-2 inhibition pyrithione zinc protivirusna zdravila SARS-COV-2 inhibicija pirition cink true false true Angleški jezik Slovenski jezik Članek v reviji 2023-04-20 12:31:00 2023-04-20 12:31:02 2023-04-21 03:31:57 0000-00-00 00:00:00 2022 0 0 Str. 2158-2168 no. 1 Vol. 37 2022 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 546.47:61:577 1475-6366 10.1080/14756366.2022.2108417 118456067 Zinc_pyrithione_is_a_potent_inhibitor_of_PLPro_and_cathepsin_L_enzymes_with_ex_vivo_inhibition_of_SARS_CoV_2_entry_and_replication.pdf Zinc_pyrithione_is_a_potent_inhibitor_of_PLPro_and_cathepsin_L_enzymes_with_ex_vivo_inhibition_of_SARS_CoV_2_entry_and_replication.pdf 1 DA088CD61DFA54A238FA99B4E3C69B68 1007ba7c8d1cdd93ca79b6ae14195181c152daca2d629e59bd3f634936798789 cea6a488-df66-11ed-a314-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=168291 https://www.tandfonline.com/doi/full/10.1080/14756366.2022.2108417 1 48d9f5de-df66-11ed-a314-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=168290 Fakulteta za kemijo in kemijsko tehnologijo 0 0 0