Novel adenosine derivatives against SARS-CoV-2 RNA-dependent RNA polymerase: an in silico perspective
Background SARS-CoV-2 is a newly emerged human coronavirus that severely affected human health and the economy. The viral RNA-dependent RNA polymerase (RdRp) is a crucial protein target to stop virus replication. The adenosine derivative, remdesivir, was authorized for emergency use 10 months ago by the United States FDA against COVID-19 despite its doubtful efficacy against SARS-CoV-2. Methods A dozen modifications based on remdesivir are tested against SARS-CoV-2 RdRp using combined molecular docking and dynamics simulation in this work. Results The results reveal a better binding affinity of 11 modifications compared to remdesivir. Compounds 8, 9, 10, and 11 show the best binding affinities against SARS-CoV-2 RdRp conformations gathered during 100 ns of the Molecular Dynamics Simulation (MDS) run (− 8.13 ± 0.45 kcal/mol, − 8.09 ± 0.67 kcal/mol, − 8.09 ± 0.64 kcal/mol, and − 8.07 ± 0.73 kcal/mol, respectively). Conclusions The present study suggests these four compounds as potential SARS-CoV-2 RdRp inhibitors, which need to be validated experimentally. Graphic abstract.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:73 |
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| Enthalten in: |
Pharmacological reports - 73(2021), 6 vom: 24. Juni, Seite 1754-1764 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sonousi, Amr [VerfasserIn] |
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| Links: |
Volltext [lizenzpflichtig] |
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| BKL: | |
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| Themen: |
Computational drug design |
| Anmerkungen: |
© Maj Institute of Pharmacology Polish Academy of Sciences 2021 |
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| doi: |
10.1007/s43440-021-00300-9 |
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| funding: |
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| 520 | |a Background SARS-CoV-2 is a newly emerged human coronavirus that severely affected human health and the economy. The viral RNA-dependent RNA polymerase (RdRp) is a crucial protein target to stop virus replication. The adenosine derivative, remdesivir, was authorized for emergency use 10 months ago by the United States FDA against COVID-19 despite its doubtful efficacy against SARS-CoV-2. Methods A dozen modifications based on remdesivir are tested against SARS-CoV-2 RdRp using combined molecular docking and dynamics simulation in this work. Results The results reveal a better binding affinity of 11 modifications compared to remdesivir. Compounds 8, 9, 10, and 11 show the best binding affinities against SARS-CoV-2 RdRp conformations gathered during 100 ns of the Molecular Dynamics Simulation (MDS) run (− 8.13 ± 0.45 kcal/mol, − 8.09 ± 0.67 kcal/mol, − 8.09 ± 0.64 kcal/mol, and − 8.07 ± 0.73 kcal/mol, respectively). Conclusions The present study suggests these four compounds as potential SARS-CoV-2 RdRp inhibitors, which need to be validated experimentally. Graphic abstract | ||
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| 700 | 1 | |a Mahran, Hanan A. |e verfasserin |4 aut | |
| 700 | 1 | |a Ibrahim, Ibrahim M. |e verfasserin |4 aut | |
| 700 | 1 | |a Ibrahim, Mohamed N. |e verfasserin |4 aut | |
| 700 | 1 | |a Elfiky, Abdo A. |e verfasserin |4 aut | |
| 700 | 1 | |a Elshemey, Wael M. |e verfasserin |4 aut | |
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