tetano
Editor, Senior Moderator
Pharmaceuticals (Basel)
. 2020 Dec 4;13(12):E443.
doi: 10.3390/ph13120443.
FDA-Approved Drugs with Potent In Vitro Antiviral Activity against Severe Acute Respiratory Syndrome Coronavirus 2
Ahmed Mostafa[SUP] 1 [/SUP], Ahmed Kandeil[SUP] 1 [/SUP], Yaseen A M M Elshaier[SUP] 2 [/SUP], Omnia Kutkat[SUP] 1 [/SUP], Yassmin Moatasim[SUP] 1 [/SUP], Adel A Rashad[SUP] 3 [/SUP], Mahmoud Shehata[SUP] 1 [/SUP], Mokhtar R Gomaa[SUP] 1 [/SUP], Noura Mahrous[SUP] 1 [/SUP], Sara H Mahmoud[SUP] 1 [/SUP], Mohamed GabAllah[SUP] 1 [/SUP], Hisham Abbas[SUP] 4 [/SUP], Ahmed El Taweel[SUP] 1 [/SUP], Ahmed E Kayed[SUP] 1 [/SUP], Mina Nabil Kamel[SUP] 1 [/SUP], Mohamed El Sayes[SUP] 1 [/SUP], Dina B Mahmoud[SUP] 5 [/SUP], Rabeh El-Shesheny[SUP] 1 [/SUP], Ghazi Kayali[SUP] 6 7 [/SUP], Mohamed A Ali[SUP] 1 [/SUP]
Affiliations
Abstract
(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[SUB]50[/SUB] of 0.32, 0.16, and 1.29 ?M, 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.
Keywords: COVID-19; SARS-CoV-2; antiviral; drug repurposing; virtual screening.
. 2020 Dec 4;13(12):E443.
doi: 10.3390/ph13120443.
FDA-Approved Drugs with Potent In Vitro Antiviral Activity against Severe Acute Respiratory Syndrome Coronavirus 2
Ahmed Mostafa[SUP] 1 [/SUP], Ahmed Kandeil[SUP] 1 [/SUP], Yaseen A M M Elshaier[SUP] 2 [/SUP], Omnia Kutkat[SUP] 1 [/SUP], Yassmin Moatasim[SUP] 1 [/SUP], Adel A Rashad[SUP] 3 [/SUP], Mahmoud Shehata[SUP] 1 [/SUP], Mokhtar R Gomaa[SUP] 1 [/SUP], Noura Mahrous[SUP] 1 [/SUP], Sara H Mahmoud[SUP] 1 [/SUP], Mohamed GabAllah[SUP] 1 [/SUP], Hisham Abbas[SUP] 4 [/SUP], Ahmed El Taweel[SUP] 1 [/SUP], Ahmed E Kayed[SUP] 1 [/SUP], Mina Nabil Kamel[SUP] 1 [/SUP], Mohamed El Sayes[SUP] 1 [/SUP], Dina B Mahmoud[SUP] 5 [/SUP], Rabeh El-Shesheny[SUP] 1 [/SUP], Ghazi Kayali[SUP] 6 7 [/SUP], Mohamed A Ali[SUP] 1 [/SUP]
Affiliations
- PMID: 33291642
- DOI: 10.3390/ph13120443
Abstract
(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[SUB]50[/SUB] of 0.32, 0.16, and 1.29 ?M, 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.
Keywords: COVID-19; SARS-CoV-2; antiviral; drug repurposing; virtual screening.