FDA-Approved Drugs with Potent In Vitro Antiviral Activity against Severe Acute Respiratory Syndrome Coronavirus 2

• Published in: Pharmaceuticals (Basel, Switzerland) Vol. 13; no. 12; p. 443
• Main Authors: Mostafa, Ahmed, Kandeil, Ahmed, A. M. M. Elshaier, Yaseen, Kutkat, Omnia, Moatasim, Yassmin, Rashad, Adel A., Shehata, Mahmoud, Gomaa, Mokhtar R., Mahrous, Noura, Mahmoud, Sara H., GabAllah, Mohamed, Abbas, Hisham, Taweel, Ahmed El, Kayed, Ahmed E., Kamel, Mina Nabil, Sayes, Mohamed El, Mahmoud, Dina B., El-Shesheny, Rabeh, Kayali, Ghazi, Ali, Mohamed A.
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 04.12.2020; MDPI AG
• Subjects: antiviral; COVID-19; drug repurposing; SARS-CoV-2; virtual screening; COVID-19; SARS-CoV-2; drug repurposing; virtual screening; antiviral
• ISSN: 1424-8247; 1424-8247
• DOI: 10.3390/ph13120443

(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 IC50 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.