Study of the Interaction of Zinc Cation with Azithromycin and its Significance in the COVID-19 Treatment: A Molecular Approach

Jacques H. Poupaert1, Blanche Aguida2, Codjo Hountondji2, *
1 Louvain Drug Research Institute, UCLouvain, Av. E. Mounier 73, B-1200 Brussels, Belgium
2 Sorbonne University; Pierre and Marie Curie Campus, “RNA Enzymology” Laboratory; SU-UR6; (Building B), 4, Place Jussieu, F-75252, Paris Cedex 05, France

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© 2020 Poupaert et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at Sorbonne University; Campus Pierre and Marie Curie, Laboratory “Enzymology of RNA” (Bât. B), SU-UR6; Case mail 60 - 7, Quai Saint-Bernard, F-75251, Paris, Cedex 05 France; E-mail:



On account of the current COVID-19 pandemic, we have explored the importance of azithromycin and zinc in the treatment of the coronavirus disease by studying the interaction between the cation Zn++ and azithromycin with the tools of the semi-empirical quantum mechanics PM3 method.


By this approach, the niche in which Zn++ is located was determined. Zn++ creates a strong clastic binding between an amine and a hydroxyl group located on the amino-hexose side-chain. Such an interaction serves as a shuttle and allows zinc cation to invade endocellular structures.


In this triple collaborative association, the role of hydroxychloroquine would be more that of a chaotropic agent at plasmic membranes, which facilitates access to the azithromycin-Zn++ equipage into key internal compartments.


Finally, we show that both azithromycin and Zn++ are susceptible to play a direct role against the replication and the assembly of SARS-CoV-2 particles.

Keywords: COVID-19, SARS-CoV-2, Coronavirus, Viral RNA, Antibiotic, Azithromycin, Erythromycin, Zn++.