Zinc pyrithione is a potent inhibitor of PLPro 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 (IC50=1.88?±?0.49 µM) and PLPro (IC50=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.
Mesh Terms:
Antiviral Agents, COVID-19 Drug Treatment, Cathepsin L, Humans, Organometallic Compounds, Pyridines, Ruthenium, SARS-CoV-2
J Enzyme Inhib Med Chem
Date: Dec. 01, 2022
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