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

(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-...

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Published inPharmaceuticals (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
LanguageEnglish
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
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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 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.
AbstractList (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.(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.
(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.
(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 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.
(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.
Author Mahmoud, Dina B.
Taweel, Ahmed El
El-Shesheny, Rabeh
Kamel, Mina Nabil
Moatasim, Yassmin
A. M. M. Elshaier, Yaseen
Mahrous, Noura
Abbas, Hisham
Kayed, Ahmed E.
Shehata, Mahmoud
Kandeil, Ahmed
Gomaa, Mokhtar R.
Ali, Mohamed A.
Kutkat, Omnia
Mostafa, Ahmed
Mahmoud, Sara H.
Rashad, Adel A.
Sayes, Mohamed El
GabAllah, Mohamed
Kayali, Ghazi
AuthorAffiliation 5 Pharmaceutics Department, National Organization for Drug Control and Research, Giza 12654, Egypt; dina_bahaa2007@yahoo.com
7 Human Link, Baabda 1109, Lebanon
3 Department of Biochemistry & Molecular Biology, Drexel University College of Medicine, Philadelphia, PA 19102, USA; aaa396@drexel.edu
4 Department of Microbiology and Immunology, Zagazig University, Zagazig 44519, Egypt; hishamabbas2008@gmail.com
6 Department of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas, Houston, TX 77030, USA
1 Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza 12622, Egypt; Ahmed.Kandeil@human-link.org (A.K.); Omnia.Abdelaziz@human-link.org (O.K.); Yasmin.Moatasim@human-link.org (Y.M.); Mahmoud.Shehata@human-link.org (M.S.); Mokhtar.Rizk@human-link.org (M.R.G.); noura.mahrous1995@gmail.com (N.M.); Sarah.Hussein@human-link.org (S.H.M.); gaballah09@gmail.com (M.G.); Ahmed.Nageh@human-link.org (A.E.T.); Ahmed.Elsayed@human-link.org (A.E.K.); mina
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– name: 1 Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza 12622, Egypt; Ahmed.Kandeil@human-link.org (A.K.); Omnia.Abdelaziz@human-link.org (O.K.); Yasmin.Moatasim@human-link.org (Y.M.); Mahmoud.Shehata@human-link.org (M.S.); Mokhtar.Rizk@human-link.org (M.R.G.); noura.mahrous1995@gmail.com (N.M.); Sarah.Hussein@human-link.org (S.H.M.); gaballah09@gmail.com (M.G.); Ahmed.Nageh@human-link.org (A.E.T.); Ahmed.Elsayed@human-link.org (A.E.K.); minanabil56@yahoo.com (M.N.K.); mohameddiaaelsayes@outlook.com (M.E.S.); ra_eny@yahoo.com (R.E.-S.)
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/33291642$$D View this record in MEDLINE/PubMed
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Issue 12
Keywords COVID-19
SARS-CoV-2
drug repurposing
virtual screening
antiviral
Language English
License https://creativecommons.org/licenses/by/4.0
Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
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Contributed equally to this work.
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Snippet (1) Background: Drug repositioning is an unconventional drug discovery approach to explore new therapeutic benefits of existing drugs. Currently, it emerges as...
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SubjectTerms antiviral
COVID-19
drug repurposing
SARS-CoV-2
virtual screening
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Title FDA-Approved Drugs with Potent In Vitro Antiviral Activity against Severe Acute Respiratory Syndrome Coronavirus 2
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