In-silico study: docking simulation and molecular dynamics of peptidomimetic fullerene-based derivatives against SARS-CoV-2 $ M^{pro} $
Abstract COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, has become a global pandemic resulting in significant morbidity and mortality. This study presents 12 new peptidomimetic fullerene-based derivatives in three groups that are investigated theoretically as SARS-CoV-2 $ M^{pro} $ inhibitors to increase the chance of treating COVID-19. Studied compounds are designed and optimized at B88-LYP/DZVP method. Molecular descriptors results show the stability and reactivity of the compounds with $ M^{pro} $, especially in the 3rd group (Ser compounds). However, Lipinski's Rule of Five values indicates that the compounds are not suitable as oral drugs. Furthermore, molecular docking simulations are carried out to investigate the binding affinity and interaction modes of the top five compounds (compounds 1, 9, 11, 2, and 10) with the $ M^{pro} $ protein, which have the lowest binding energy. Molecular dynamics simulations are also performed to evaluate the stability of the protein–ligand complexes with compounds 1 and 9 and compare them with natural substrate interaction. The analysis of RMSD, H-bonds, Rg, and SASA indicates that both compounds 1 (Gly-α acid) and 9 (Ser-α acid) have good stability and strong binding affinity with the $ M^{pro} $ protein. However, compound 9 shows slightly better stability and binding affinity compared to compound 1..
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
3 Biotech - 13(2023), 6 vom: 13. Mai |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Saleh, Noha A. [VerfasserIn] |
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| Links: |
Volltext [lizenzpflichtig] |
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| Themen: |
COVID-19 |
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| Anmerkungen: |
© King Abdulaziz City for Science and Technology 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
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| doi: |
10.1007/s13205-023-03608-w |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
OLC2143685947 |
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| 520 | |a Abstract COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, has become a global pandemic resulting in significant morbidity and mortality. This study presents 12 new peptidomimetic fullerene-based derivatives in three groups that are investigated theoretically as SARS-CoV-2 $ M^{pro} $ inhibitors to increase the chance of treating COVID-19. Studied compounds are designed and optimized at B88-LYP/DZVP method. Molecular descriptors results show the stability and reactivity of the compounds with $ M^{pro} $, especially in the 3rd group (Ser compounds). However, Lipinski's Rule of Five values indicates that the compounds are not suitable as oral drugs. Furthermore, molecular docking simulations are carried out to investigate the binding affinity and interaction modes of the top five compounds (compounds 1, 9, 11, 2, and 10) with the $ M^{pro} $ protein, which have the lowest binding energy. Molecular dynamics simulations are also performed to evaluate the stability of the protein–ligand complexes with compounds 1 and 9 and compare them with natural substrate interaction. The analysis of RMSD, H-bonds, Rg, and SASA indicates that both compounds 1 (Gly-α acid) and 9 (Ser-α acid) have good stability and strong binding affinity with the $ M^{pro} $ protein. However, compound 9 shows slightly better stability and binding affinity compared to compound 1. | ||
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