LAPSE:2023.2762
Published Article
LAPSE:2023.2762
Multi-Phase In Silico Discovery of Potential SARS-CoV-2 RNA-Dependent RNA Polymerase Inhibitors among 3009 Clinical and FDA-Approved Related Drugs
February 21, 2023
Abstract
Proceeding our prior studies of SARS-CoV-2, the inhibitory potential against SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) has been investigated for a collection of 3009 clinical and FDA-approved drugs. A multi-phase in silico approach has been employed in this study. Initially, a molecular fingerprint experiment of Remdesivir (RTP), the co-crystallized ligand of the examined protein, revealed the most similar 150 compounds. Among them, 30 compounds were selected after a structure similarity experiment. Subsequently, the most similar 30 compounds were docked against SARS-CoV-2 RNA-dependent RNA polymerase (PDB ID: 7BV2). Aloin 359, Baicalin 456, Cefadroxil 1273, Sophoricoside 1459, Hyperoside 2109, and Vitexin 2286 exhibited the most precise binding modes, as well as the best binding energies. To confirm the obtained results, MD simulations experiments have been conducted for Hyperoside 2109, the natural flavonoid glycoside that exhibited the best docking scores, against RdRp (PDB ID: 7BV2) for 100 ns. The achieved results authenticated the correct binding of 2109, showing low energy and optimum dynamics. Our team presents these outcomes for scientists all over the world to advance in vitro and in vivo examinations against COVID-19 for the promising compounds.
Proceeding our prior studies of SARS-CoV-2, the inhibitory potential against SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) has been investigated for a collection of 3009 clinical and FDA-approved drugs. A multi-phase in silico approach has been employed in this study. Initially, a molecular fingerprint experiment of Remdesivir (RTP), the co-crystallized ligand of the examined protein, revealed the most similar 150 compounds. Among them, 30 compounds were selected after a structure similarity experiment. Subsequently, the most similar 30 compounds were docked against SARS-CoV-2 RNA-dependent RNA polymerase (PDB ID: 7BV2). Aloin 359, Baicalin 456, Cefadroxil 1273, Sophoricoside 1459, Hyperoside 2109, and Vitexin 2286 exhibited the most precise binding modes, as well as the best binding energies. To confirm the obtained results, MD simulations experiments have been conducted for Hyperoside 2109, the natural flavonoid glycoside that exhibited the best docking scores, against RdRp (PDB ID: 7BV2) for 100 ns. The achieved results authenticated the correct binding of 2109, showing low energy and optimum dynamics. Our team presents these outcomes for scientists all over the world to advance in vitro and in vivo examinations against COVID-19 for the promising compounds.
Record ID
Keywords
FDA-approved drugs, MD simulations, molecular docking, molecular fingerprints, SARS-CoV-2 RNA-dependent RNA polymerase, structural similarity
Subject
Suggested Citation
Elkaeed EB, Elkady H, Belal A, Alsfouk BA, Ibrahim TH, Abdelmoaty M, Arafa RK, Metwaly AM, Eissa IH. Multi-Phase In Silico Discovery of Potential SARS-CoV-2 RNA-Dependent RNA Polymerase Inhibitors among 3009 Clinical and FDA-Approved Related Drugs. (2023). LAPSE:2023.2762
Author Affiliations
Elkaeed EB: Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, Riyadh 13713, Saudi Arabia [ORCID]
Elkady H: Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt [ORCID]
Belal A: Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia [ORCID]
Alsfouk BA: Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah Bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia [ORCID]
Ibrahim TH: Drug Design and Discovery Laboratory, Zewail City of Science and Technology, Cairo 12578, Egypt; Biomedical Sciences Program, University of Science and Technology, Zewail City of Science and Technology, Cairo 12578, Egypt
Abdelmoaty M: Drug Design and Discovery Laboratory, Zewail City of Science and Technology, Cairo 12578, Egypt
Arafa RK: Drug Design and Discovery Laboratory, Zewail City of Science and Technology, Cairo 12578, Egypt; Biomedical Sciences Program, University of Science and Technology, Zewail City of Science and Technology, Cairo 12578, Egypt [ORCID]
Metwaly AM: Pharmacognosy and Medicinal Plants Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt; Biopharmaceutical Products Research Department, Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and T [ORCID]
Eissa IH: Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt [ORCID]
Elkady H: Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt [ORCID]
Belal A: Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia [ORCID]
Alsfouk BA: Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah Bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia [ORCID]
Ibrahim TH: Drug Design and Discovery Laboratory, Zewail City of Science and Technology, Cairo 12578, Egypt; Biomedical Sciences Program, University of Science and Technology, Zewail City of Science and Technology, Cairo 12578, Egypt
Abdelmoaty M: Drug Design and Discovery Laboratory, Zewail City of Science and Technology, Cairo 12578, Egypt
Arafa RK: Drug Design and Discovery Laboratory, Zewail City of Science and Technology, Cairo 12578, Egypt; Biomedical Sciences Program, University of Science and Technology, Zewail City of Science and Technology, Cairo 12578, Egypt [ORCID]
Metwaly AM: Pharmacognosy and Medicinal Plants Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt; Biopharmaceutical Products Research Department, Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and T [ORCID]
Eissa IH: Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, Egypt [ORCID]
Journal Name
Processes
Volume
10
Issue
3
First Page
530
Year
2022
Publication Date
2022-03-07
ISSN
2227-9717
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PII: pr10030530, Publication Type: Journal Article
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LAPSE:2023.2762
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https://doi.org/10.3390/pr10030530
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