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Large-scale efforts have been persistently undertaken for medical prophylaxis and treatment of COVID-19 disasters worldwide. A variety of novel viral spike protein-targeted vaccines have been extensively distributed for global inoculation based on accelerated approval. With concerns of emerging spike protein mutations, we revisited the early but inconclusive clinical interest in the repurposed combination of azithromycin (AZT) and zinc supplements with safety advantages. The aim of this study is to provide in vitro proof of concept for IκBα associated rapid and synergistic suppression of angiotensin-converting enzymes 2 (ACE2) following combination treatments with AZT plus zinc sulfate in two human airway cells with ACE2 expression, Calu-3 and H322M, representative cells of the human upper and lower airway origin respectively. Clinical timing of AZT combined with zinc is indicated based on suppression of the key cellular entry molecule, ACE2, of SARS-CoV-2.

The Effect of Azithromycin Plus Zinc Sulfate on ACE2 Expression through IκBα of Human Respiratory Cells in SARS-CoV-2: In Vitro Study