Mucoactive drugs block SARS-CoV-2 infection Coronavirus Disease COVID DrugDiscovery Mucoactive Mucociliary biorxivpreprint UofAlabama
By Pooja Toshniwal PahariaFeb 7 2023Reviewed by Benedette Cuffari, M.Sc. In a recent study published on the bioRxiv* preprint server, researchers evaluate the effects of mucociliary active molecules on severe acute respiratory syndrome coronavirus 2 infection in vitro.
SARS-CoV-2 infection destroys ciliated respiratory cells and disrupts mucociliary transport functions. Altered MCT could prolong COVID-19 and increase the risk of secondary long-term complications due to dysregulated immune responses and pulmonary damage. Thus, MCT-augmenting drugs could improve airway epithelial barrier functions, reduce SARS-CoV-2 replication, and ultimately improve COVID-19 outcomes.
To explore these agents' mechanistic and functional aspects, human bronchial epithelial cells were grown and differentiated in an air-liquid interface . Among the tested drugs, ARINA-1, the most effective, was investigated further using donor cell lines referred to as WT-128, WT-148, WT-152, WT-158, and WT-210.
The cytotoxicity of all mucociliary active molecules, except ARINA-1, was measured using non-radioactive cytotoxicity assays based on lactate dehydrogenase release. ARINA-1 cytotoxicity was assessed using cell viability assays measuring intracellular adenosine triphosphate levels.Study findings To some extent, all mucociliary active compounds inhibited SARS-CoV-2 proliferation in HBECs, among which camostat mesylate, ARINA-1, and HA conferred the greatest degree of protection.
Drug Discovery eBook Compilation of the top interviews, articles, and news in the last year. Download a free copy Anti-SARS-CoV-2 activity of the mucoactive agents tested in well-differentiated primary HBE cells. A) Effect on the viral copy number measured by the RT-qPCR caused by ivacaftor at the concentrations shown on the graph. B) Data from graph in A) were converted to percent of viral inhibition. C-D), E-F) and G-H) As in , but using the compounds PAAG, HA and ARINA-1, respectively.
Histopathology studies showed that ARINA-1 protects primary HBE cells from SARS-CoV-2-mediated cytopathology. A-L) Representative photo micrographs of HBEC cross-sections with the immunohistochemistry and treatments. Each row corresponds to the immunohistochemistry using the antibody against the cell marker shown at the left, and each column corresponds to the treatment shown above the upper pictures. SARS-CoV-2 caused cilia shortening and loss in saline-treated cells .
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