Journal
PHARMACEUTICS
Volume 14, Issue 5, Pages -Publisher
MDPI
DOI: 10.3390/pharmaceutics14050899
Keywords
hydroxychloroquine; COVID-19; ionophore; zinc; clioquinol
Categories
Funding
- Janssen Pharmaceuticals
- Science Foundation Ireland [12/RC/2275_P2]
- Science Foundation Ireland (SFI) [12/RC/2275_P2] Funding Source: Science Foundation Ireland (SFI)
Ask authors/readers for more resources
Drug-mediated correction of abnormal biological zinc homeostasis is important for treating neurodegeneration, cancer, and viral infections. Our study provides evidence that hydroxychloroquine, a potential treatment for COVID-19, does not bind and transport zinc through ionophoric mechanisms as previously claimed.
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available