Zinc pyrithione is a potent inhibitor of PL and cathepsin L enzymes with inhibition of SARS-CoV-2 entry and replication.

Zinc pyrithione (), together with its analogues - and ruthenium pyrithione complex , were synthesised and evaluated for the stability in biologically relevant media and anti-SARS-CoV-2 activity. Zinc pyrithione revealed potent inhibition of cathepsin L (IC=1.88 ± 0.49 µM) and PL (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 system derived from primary human lung tissue. Zinc complexes - expressed comparable inhibition. On the contrary, ruthenium complex and the ligand pyrithione 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.