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 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.
Keywords: Antiviral agents; SARS-CoV-2; inhibition; pyrithione; zinc.
【저자키워드】 SARS-CoV-2, inhibition, Antiviral agents, pyrithione, zinc., 【초록키워드】 COVID-19, Zinc, Antiviral, media, in vitro, antiviral activity, Replication, stability, Antiviral agents, therapeutic, ruthenium, therapeutic agent, Enzymes, pyrithione, Ligand, Anti-SARS-CoV-2 Activity, cathepsin L, Ex vivo, enzyme, SARS-CoV-2 entry, complex, contrary, human lung tissue, analogue, effective, Zinc complexes, Zinc pyrithione, involved, assays, evaluated, expressed, comparable, complexes, Pro, synthesised, 【제목키워드】 inhibitor, Ex vivo, enzyme, Pro,