Abstract
Drug repositioning has been used extensively since the beginning of the COVID-19 pandemic in an attempt to identify antiviral molecules for use in human therapeutics. Hydroxychloroquine and azithromycin have shown inhibitory activity against SARS-CoV-2 replication in different cell lines. Based on such in vitro data and despite the weakness of preclinical assessment, many clinical trials were set up using these molecules. In the present study, we show that hydroxychloroquine and azithromycin alone or combined does not block SARS-CoV-2 replication in human bronchial airway epithelia. When tested in a Syrian hamster model, hydroxychloroquine and azithromycin administrated alone or combined displayed no significant effect on viral replication, clinical course of the disease and lung impairments, even at high doses. Hydroxychloroquine quantification in lung tissues confirmed strong exposure to the drug, above in vitro inhibitory concentrations. Overall, this study does not support the use of hydroxychloroquine and azithromycin as antiviral drugs for the treatment of SARS-CoV-2 infections.
Keywords: Antivirals; Azithromycin; COVID-19; Coronavirus; Ex vivo; Human airway epithelium; Hydroxychloroquine; In vivo; SARS-CoV-2; Syrian hamster.
【저자키워드】 COVID-19, SARS-CoV-2, coronavirus, Azithromycin, Hydroxychloroquine, antivirals, in vivo, Ex vivo, Human airway epithelium, Syrian hamster., 【초록키워드】 Treatment, clinical trial, COVID-19 pandemic, Human, lung, drug, in vitro, antiviral drug, airway, Clinical course, viral replication, quantification, SARS-CoV-2 infections, SARS-CoV-2 replication, cell lines, Support, no significant effect, lung tissue, weakness, doses, inhibitory activity, inhibitory, in vitro data, airway epithelia, concentrations, shown, tested, identify, the disease, antiviral molecule, use of hydroxychloroquine, 【제목키워드】 effective,