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Review
. 2020 Sep 1;13(9):228.
doi: 10.3390/ph13090228.

Zinc(II)-The Overlooked Éminence Grise of Chloroquine's Fight against COVID-19?

Aleksandra Hecel  1 , Małgorzata Ostrowska  1 , Kamila Stokowa-Sołtys  1 , Joanna Wątły  1 , Dorota Dudek  1 , Adriana Miller  1 , Sławomir Potocki  1 , Agnieszka Matera-Witkiewicz  2 , Alicia Dominguez-Martin  3 , Henryk Kozłowski  1   4 , Magdalena Rowińska-Żyrek  1
Affiliations
Review

Zinc(II)-The Overlooked Éminence Grise of Chloroquine's Fight against COVID-19?

Aleksandra Hecel et al. Pharmaceuticals (Basel). .

Abstract

Zn(II) is an inhibitor of SARS-CoV-2's RNA-dependent RNA polymerase, and chloroquine and hydroxychloroquine are Zn(II) ionophores-this statement gives a curious mind a lot to think about. We show results of the first clinical trials on chloroquine (CQ) and hydroxychloroquine (HCQ) in the treatment of COVID-19, as well as earlier reports on the anticoronaviral properties of these two compounds and of Zn(II) itself. Other FDA-approved Zn(II) ionophores are given a decent amount of attention and are thought of as possible COVID-19 therapeutics.

Keywords: 2019-nCoV; COVID-19; SARS-CoV-2; Zn(II) ionophores; chloroquine; hydroxy- chloroquine.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
(a) Diagram and structure of the SARS-CoV nsp12 protein indicating protein domains (NiRAN, interface, fingers, thumb and palm), conserved motifs (AN, BN, CN, G, F, A, B, C, D) and zinc(II) binding sites (red spheres). Enlarged zinc(II) binding sites of nsp12 protein placed in: (b) interface region and (c) fingers region. The figure was generated using PyMOL [41]. PDB entry: 7BTF [42]. Figures based on [21,22].
Figure 2
Figure 2
Classification of chosen coronaviruses. Species described in this section were marked in red.
Figure 3
Figure 3
Potential drugs involved in clinical trials against COVID-19 classified in individual categories [60].
Figure 4
Figure 4
An overview of zinc(II) ionophores discussed in this work: chloroquine (CQ), hydroxychloroquine (HCQ), hinokitol (HK), dithiocarbamates (DTCs), pyrrolidine dithiocarbamate (PDTC), pyrithione (PT), 8-hydroxyquinoline (PBT2), clioquinol, quercetin and zincophorin.
See this image and copyright information in PMC

References

    1. Te Velthuis A.J.W., van den Worm S.H.E., Sims A.C., Baric R.S., Snijder E.J., van Hemert M.J. Zn2+ Inhibits Coronavirus and Arterivirus RNA Polymerase Activity In Vitro and Zinc Ionophores Block the Replication of These Viruses in Cell Culture. PLoS Pathog. 2010;6:e1001176. doi: 10.1371/journal.ppat.1001176. - DOI - PMC - PubMed
    1. Xue J., Moyer A., Peng B., Wu J., Hannafon B.N., Ding W.-Q. Chloroquine Is a Zinc Ionophore. PLoS ONE. 2014;9:e109180. doi: 10.1371/journal.pone.0109180. - DOI - PMC - PubMed
    1. Gao J., Tian Z., Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci. Trends. 2020;14:72–73. doi: 10.5582/bst.2020.01047. - DOI - PubMed
    1. Gautret P., Lagier J.-C., Parola P., van Hoang T., Meddeb L., Mailhe M., Doudier B., Courjon J., Giordanengo V., Vieira V.E., et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: Results of an open-label non-randomized clinical trial. Int. J. Antimicrob. Agents. 2020;56:105949. doi: 10.1016/j.ijantimicag.2020.105949. - DOI - PMC - PubMed
    1. Yu B., Li C., Chen P., Zhou N., Wang L., Li J., Jiang H., Wang D.-W. Erratum to: Low dose of hydroxychloroquine reduces fatality of critically ill patients with COVID-19. Sci. China Life Sci. 2020 doi: 10.1007/s11427-020-1751-3. - DOI - PMC - PubMed

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