RT Journal Article
SR Electronic
T1 Zinc pyrithione is a potent inhibitor of PL<sup>Pro</sup> and cathepsin L enzymes with <em>ex vivo</em> inhibition of SARS-CoV-2 entry and replication
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.03.03.482819
DO 10.1101/2022.03.03.482819
A1 Kladnik, Jerneja
A1 Dolinar, Ana
A1 Kljun, Jakob
A1 Perea, David
A1 Grau-Expósito, Judith
A1 Genescà, Meritxell
A1 Novinec, Marko
A1 Buzon, Maria J.
A1 Turel, Iztok
YR 2022
UL http://biorxiv.org/content/early/2022/03/04/2022.03.03.482819.abstract
AB As SARS-CoV-2 triggered a global health crisis, there is an urgent need to provide patients with safe, effective, accessible, and preferably oral therapeutics for COVID-19 that complement mRNA vaccines. Zinc compounds are widely known for their antiviral properties. Therefore, we have prepared a library of zinc complexes with pyrithione (1-hydroxy-2(1H)-pyridinethione) and its analogues, all of which showed promising in vitro inhibition of cathepsin L, an enzyme involved in SARS-CoV-2 entry, and PLPro, an enzyme involved in SARS-CoV-2 replication both in (sub)micromolar range. Zinc pyrithione 1a is a well-established, commercially available antimicrobial agent and was therefore selected for further evaluation of its SARS-CoV-2 entry and replication inhibition in an ex vivo system derived from primary human lung tissue. Our results suggest that zinc pyrithione complex 1a provides a multitarget approach to combat SARS-CoV-2 and should be considered for repurposing as a potential therapeutic against the insidious COVID-19 disease.Featured image In our study, we show that zinc pyrithione holds immense potential for the development of a possible out-patient treatment for SARS-CoV-2 due to its inhibition of viral entry and replication.Competing Interest StatementThe authors have declared no competing interest.