Zinc pyrithione is a potent inhibitor of PL$^{Pro}$ and cathepsin L enzymes with ex vivo inhibition of SARS-CoV-2 entry and replication

Kladnik, Jerneja (avtor), Dolinar, Ana (avtor), Kljun, Jakob (avtor), Perea, David (avtor), Grau-Expósito, Judith (avtor), Genescà, Meritxell (avtor), Novinec, Marko (avtor), Buzon, Maria J. (avtor), Turel, Iztok (avtor)

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.

• Jezik: Angleški jezik
• Ključne besede: antiviral agents, SARS-CoV-2, inhibition, pyrithione, zinc
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FKKT - Fakulteta za kemijo in kemijsko tehnologijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2022
• Št. strani: Str. 2158-2168
• Številčenje: Vol. 37, no. 1
• PID: 20.500.12556/RUL-145390
• UDK: 546.47:61:577
• ISSN pri članku: 1475-6366
• DOI: 10.1080/14756366.2022.2108417
• COBISS.SI-ID: 118456067
• Datum objave v RUL: 20.04.2023

Gradivo je del revije

• Naslov: Journal of enzyme inhibition and medicinal chemistry
• Skrajšan naslov: J. enzyme inhib. med. chem.
• Založnik: Taylor & Francis
• ISSN: 1475-6366
• COBISS.SI-ID: 512255001

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: protivirusna zdravila, SARS-COV-2, inhibicija, pirition, cink