Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia.
Infectious Diseases Department, Vall d'Hebron Research Institute (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, VHIR Task Force COVID-19, Barcelona, Spain.
J Enzyme Inhib Med Chem. 2022 Dec;37(1):2158-2168. doi: 10.1080/14756366.2022.2108417.
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.
吡啶硫酮锌（）及其类似物 - 和钌吡啶硫酮配合物，被合成并评估了在生物相关介质中的稳定性和抗 SARS-CoV-2 活性。吡啶硫酮锌对参与 SARS-CoV-2 进入和复制的组织蛋白酶 L（IC=1.88±0.49μM）和 PL（IC=0.50±0.07μM）表现出有效的抑制作用，同时在源自人原代肺组织的系统中表现出抗病毒进入和复制特性。锌配合物 - 表达出相当的抑制作用。相反，钌配合物 和配体吡啶硫酮 本身在上述测定中表现出较差的抑制作用，表明选择金属核和金属配合物的结构对于抗病毒活性的重要性。需要针对 COVID-19 的安全、有效且最好是在家中口服的治疗方法，因此，吡啶硫酮锌（也可商业获得）可被视为针对 SARS-CoV-2 的潜在治疗剂。
