(1) Background: Drug repositioning is an unconventional drug discovery approach to explore new therapeutic benefits of existing drugs. Currently, it emerges as a rapid avenue to alleviate the COVID-19 pandemic disease. (2) Methods: Herein, we tested the antiviral activity of anti-microbial and anti-inflammatory Food and Drug Administration (FDA)-approved drugs, commonly prescribed to relieve respiratory symptoms, against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the viral causative agent of the COVID-19 pandemic. (3) Results: Of these FDA-approved antimicrobial drugs, Azithromycin, Niclosamide, and Nitazoxanide showed a promising ability to hinder the replication of a SARS-CoV-2 isolate, with IC 50 of 0.32, 0.16, and 1.29 µM, respectively. We provided evidence that several antihistamine and anti-inflammatory drugs could partially reduce SARS-CoV-2 replication in vitro. Furthermore, this study showed that Azithromycin can selectively impair SARS-CoV-2 replication, but not the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). A virtual screening study illustrated that Azithromycin, Niclosamide, and Nitazoxanide bind to the main protease of SARS-CoV-2 (Protein data bank (PDB) ID: 6lu7) in binding mode similar to the reported co-crystalized ligand. Also, Niclosamide displayed hydrogen bond (HB) interaction with the key peptide moiety GLN: 493A of the spike glycoprotein active site. (4) Conclusions: The results suggest that Piroxicam should be prescribed in combination with Azithromycin for COVID-19 patients.
【저자키워드】 COVID-19, Drug repurposing, SARS-CoV-2, Antiviral, Virtual screening, 【초록키워드】 Drug discovery, Azithromycin, Anti-inflammatory, COVID-19 pandemic, spike glycoprotein, peptide, drugs, drug, protease, in vitro, antiviral activity, MERS-CoV, coronavirus 2, Replication, nitazoxanide, respiratory, disease, SARS-CoV-2 replication, COVID-19 patients, binding, niclosamide, food, Evidence, Combination, Hydrogen bond, Ligand, Interaction, Middle East, respiratory symptoms, Therapeutic benefit, anti-inflammatory drug, PDB, approach, tested, reported, provided, reduce, impair, alleviate, antimicrobial drugs, Piroxicam, 【제목키워드】 drug, coronavirus 2, activity, respiratory, potent,