Zinc supplement augments the suppressive effects of repurposed drugs of NF-kappa B inhibitor on ACE2 expression in human lung cell lines in vitro.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a vast number of infections and fatalities worldwide. As the development and safety validation of effective vaccines are ongoing, drug repurposing is most efficient approach to search FDA approved agents against coronavirus disease 2019 (COVID-19). In the present study, we found that endogenous ACE2 expressions could be detected in H322M and Calu-3 cell lines, as well as their ACE2 mRNA and protein expressions were suppressed by pyrrolidine dithiocarbamate (PDTC), a NF-kappa B inhibitor, in dose- and time-dependent manners. Moreover, N-acetyl-cysteine (NAC) pretreatment reversed PDTC-induced ACE2 suppression, as well as the combined treatment of hydrogen peroxide and knockdown of p50 subunit of NF-kappa B by siRNA reduced ACE2 expression in H322M cells. In addition, anthelmintic drug triclabendazole and antiprotozoal drug emetine, repurposed drugs of NF-kappa B inhibitor, also inhibited ACE2 mRNA and protein expressions in H322M cells. Moreover, zinc supplement augmented the suppressive effects of triclabendazole and emetine on ACE2 suppression in H322M and Calu-3 cells. Taken together, these results indicate that ACE2 expression is modulated by reactive oxygen species (ROS) and NF-kappa B signal in human lung cell lines, and zinc combination with triclabendazole or emetine has the clinical potential for the prevention and treatment of COVID-19.

Azithromycin Plus Zinc Sulfate Rapidly and Synergistically Suppresses IκBα-Mediated In Vitro Human Airway Cell ACE2 Expression for SARS-CoV-2 Entry

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 vaccine preparations have recently been clinically distributed based on accelerated approval. We revisited the early but inconclusive clinical interest in the combination of azithromycin and zinc sulfate repurposing with safety advantages. In vitro proof of concept was provided for rapid and synergistic suppression of ACE2 expression following treatments in human airway cells, Calu-3 and H322M. The two representative ACE2-expressing human airway cells indicate the upper and lower respiratory tracts. Prophylactic and early therapeutic roles of azithromycin combined with zinc are proposed for virus cellular entry prevention potential bridging to effective antibody production.