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

• Príomhchruthaitheoirí: Ahmed Mostafa (Údar), Ahmed Kandeil (Údar), Yaseen A. M. M. Elshaier (Údar), Omnia Kutkat (Údar), Yassmin Moatasim (Údar), Adel A. Rashad (Údar), Mahmoud Shehata (Údar), Mokhtar R. Gomaa (Údar), Noura Mahrous (Údar), Sara H. Mahmoud (Údar), Mohamed GabAllah (Údar), Hisham Abbas (Údar), Ahmed El Taweel (Údar), Ahmed E. Kayed (Údar), Mina Nabil Kamel (Údar), Mohamed El Sayes (Údar), Dina B. Mahmoud (Údar), Rabeh El-Shesheny (Údar), Ghazi Kayali (Údar), Mohamed A. Ali (Údar)
• Formáid: LEABHAR
• Foilsithe / Cruthaithe: MDPI AG, 2020-12-01T00:00:00Z.
• Ábhair: article
• Rochtain ar líne: Connect to this object online.

Achoimre

(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.

Cur síos ar an mír

10.3390/ph13120443
1424-8247