Hydroxychloroquine Does Not Function as a Direct Zinc Ionophore.
COVID-19
clioquinol
hydroxychloroquine
ionophore
zinc
Journal
Pharmaceutics
ISSN: 1999-4923
Titre abrégé: Pharmaceutics
Pays: Switzerland
ID NLM: 101534003
Informations de publication
Date de publication:
20 Apr 2022
20 Apr 2022
Historique:
received:
18
03
2022
revised:
11
04
2022
accepted:
15
04
2022
entrez:
28
5
2022
pubmed:
29
5
2022
medline:
29
5
2022
Statut:
epublish
Résumé
Drug-mediated correction of abnormal biological zinc homeostasis could provide new routes to treating neurodegeneration, cancer, and viral infections. Designing therapeutics to facilitate zinc transport intracellularly is hampered by inadequate concentrations of endogenous zinc, which is often protein-bound in vivo. We found strong evidence that hydroxychloroquine, a drug used to treat malaria and employed as a potential treatment for COVID-19, does not bind and transport zinc across biological membranes through ionophoric mechanisms, contrary to recent claims. In vitro complexation studies and liposomal transport assays are correlated with cellular zinc assays in A549 lung epithelial cells to confirm the indirect mechanism of hydroxychloroquine-mediated elevation in intracellular zinc without ionophorism. Molecular simulations show hydroxychloroquine-triggered helix perturbation in zinc-finger protein without zinc chelation, a potential alternative non-ionophoric mechanism.
Identifiants
pubmed: 35631485
pii: pharmaceutics14050899
doi: 10.3390/pharmaceutics14050899
pmc: PMC9147311
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Science Foundation Ireland
ID : 12/RC/2275_P2
Pays : Ireland
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