In Silico Evaluation of Sesquiterpenes and Benzoxazinoids Phytotoxins against M<sup>pro</sup>, RNA Replicase and Spike Protein of SARS-CoV-2 by Molecular Dynamics. Inspired by Nature
In the work described here, a number of sesquiterpenes and benzoxazinoids from natural sources, along with their easily accessible derivatives, were evaluated against the main protease, RNA replicase and spike glycoprotein of SARS-CoV-2 by molecular docking. These natural products and their derivati...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-08-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/14/9/599 |
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| author | Francisco J. R. Mejías Alexandra G. Durán Nuria Chinchilla Rosa M. Varela José A. Álvarez José M. G. Molinillo Francisco García-Cozar Francisco A. Macías |
| author_facet | Francisco J. R. Mejías Alexandra G. Durán Nuria Chinchilla Rosa M. Varela José A. Álvarez José M. G. Molinillo Francisco García-Cozar Francisco A. Macías |
| author_sort | Francisco J. R. Mejías |
| collection | DOAJ |
| description | In the work described here, a number of sesquiterpenes and benzoxazinoids from natural sources, along with their easily accessible derivatives, were evaluated against the main protease, RNA replicase and spike glycoprotein of SARS-CoV-2 by molecular docking. These natural products and their derivatives have previously shown remarkable antiviral activities. The most relevant compounds were the 4-fluoro derivatives of santamarine, reynosin and 2-amino-3<i>H</i>-phenoxazin-3-one in terms of the docking score. Those compounds fulfill the Lipinski’s rule, so they were selected for the analysis by molecular dynamics, and the kinetic stabilities of the complexes were assessed. The addition of the 4-fluorobenzoate fragment to the natural products enhances their potential against all of the proteins tested, and the complex stability after 50 ns validates the inhibition calculated. The derivatives prepared from reynosin and 2-amino-3<i>H</i>-phenoxazin-3-one are able to generate more hydrogen bonds with the M<sup>pro</sup>, thus enhancing the stability of the protein–ligand and generating a long-term complex for inhibition. The 4-fluoro derivate of santamarine and reynosin shows to be really active against the spike protein, with the RMSD site fluctuation lower than 1.5 Å. Stabilization is mainly achieved by the hydrogen-bond interactions, and the stabilization is improved by the 4-fluorobenzoate fragment being added. Those compounds tested in silico reach as candidates from natural sources to fight this virus, and the results concluded that the addition of the 4-fluorobenzoate fragment to the natural products enhances their inhibition potential against the main protease, RNA replicase and spike protein of SARS-CoV-2. |
| first_indexed | 2024-03-09T22:20:31Z |
| format | Article |
| id | doaj.art-c6758285cdfb4266b267392856bec2e5 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-09T22:20:31Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-c6758285cdfb4266b267392856bec2e52023-11-23T19:16:28ZengMDPI AGToxins2072-66512022-08-0114959910.3390/toxins14090599In Silico Evaluation of Sesquiterpenes and Benzoxazinoids Phytotoxins against M<sup>pro</sup>, RNA Replicase and Spike Protein of SARS-CoV-2 by Molecular Dynamics. Inspired by NatureFrancisco J. R. Mejías0Alexandra G. Durán1Nuria Chinchilla2Rosa M. Varela3José A. Álvarez4José M. G. Molinillo5Francisco García-Cozar6Francisco A. Macías7Allelopathy Group, Department of Organic Chemistry, Institute of Biomolecules (INBIO), Campus CEIA3, School of Science, University of Cádiz, C/República Saharaui, 7, 11510 Puerto Real, SpainAllelopathy Group, Department of Organic Chemistry, Institute of Biomolecules (INBIO), Campus CEIA3, School of Science, University of Cádiz, C/República Saharaui, 7, 11510 Puerto Real, SpainAllelopathy Group, Department of Organic Chemistry, Institute of Biomolecules (INBIO), Campus CEIA3, School of Science, University of Cádiz, C/República Saharaui, 7, 11510 Puerto Real, SpainAllelopathy Group, Department of Organic Chemistry, Institute of Biomolecules (INBIO), Campus CEIA3, School of Science, University of Cádiz, C/República Saharaui, 7, 11510 Puerto Real, SpainDepartment of Physical Chemistry, Faculty of Sciences, INBIO, University of Cádiz, 11510 Puerto Real, SpainAllelopathy Group, Department of Organic Chemistry, Institute of Biomolecules (INBIO), Campus CEIA3, School of Science, University of Cádiz, C/República Saharaui, 7, 11510 Puerto Real, SpainDepartment of Biomedicine, Biotechnology and Public Health, University of Cádiz and Institute of Biomedical Research Cádiz (INIBICA), 11009 Cádiz, SpainAllelopathy Group, Department of Organic Chemistry, Institute of Biomolecules (INBIO), Campus CEIA3, School of Science, University of Cádiz, C/República Saharaui, 7, 11510 Puerto Real, SpainIn the work described here, a number of sesquiterpenes and benzoxazinoids from natural sources, along with their easily accessible derivatives, were evaluated against the main protease, RNA replicase and spike glycoprotein of SARS-CoV-2 by molecular docking. These natural products and their derivatives have previously shown remarkable antiviral activities. The most relevant compounds were the 4-fluoro derivatives of santamarine, reynosin and 2-amino-3<i>H</i>-phenoxazin-3-one in terms of the docking score. Those compounds fulfill the Lipinski’s rule, so they were selected for the analysis by molecular dynamics, and the kinetic stabilities of the complexes were assessed. The addition of the 4-fluorobenzoate fragment to the natural products enhances their potential against all of the proteins tested, and the complex stability after 50 ns validates the inhibition calculated. The derivatives prepared from reynosin and 2-amino-3<i>H</i>-phenoxazin-3-one are able to generate more hydrogen bonds with the M<sup>pro</sup>, thus enhancing the stability of the protein–ligand and generating a long-term complex for inhibition. The 4-fluoro derivate of santamarine and reynosin shows to be really active against the spike protein, with the RMSD site fluctuation lower than 1.5 Å. Stabilization is mainly achieved by the hydrogen-bond interactions, and the stabilization is improved by the 4-fluorobenzoate fragment being added. Those compounds tested in silico reach as candidates from natural sources to fight this virus, and the results concluded that the addition of the 4-fluorobenzoate fragment to the natural products enhances their inhibition potential against the main protease, RNA replicase and spike protein of SARS-CoV-2.https://www.mdpi.com/2072-6651/14/9/599molecular dynamicsdockingSARS-CoV-2COVID-19sesquiterpenebenzoxazinoid |
| spellingShingle | Francisco J. R. Mejías Alexandra G. Durán Nuria Chinchilla Rosa M. Varela José A. Álvarez José M. G. Molinillo Francisco García-Cozar Francisco A. Macías In Silico Evaluation of Sesquiterpenes and Benzoxazinoids Phytotoxins against M<sup>pro</sup>, RNA Replicase and Spike Protein of SARS-CoV-2 by Molecular Dynamics. Inspired by Nature Toxins molecular dynamics docking SARS-CoV-2 COVID-19 sesquiterpene benzoxazinoid |
| title | In Silico Evaluation of Sesquiterpenes and Benzoxazinoids Phytotoxins against M<sup>pro</sup>, RNA Replicase and Spike Protein of SARS-CoV-2 by Molecular Dynamics. Inspired by Nature |
| title_full | In Silico Evaluation of Sesquiterpenes and Benzoxazinoids Phytotoxins against M<sup>pro</sup>, RNA Replicase and Spike Protein of SARS-CoV-2 by Molecular Dynamics. Inspired by Nature |
| title_fullStr | In Silico Evaluation of Sesquiterpenes and Benzoxazinoids Phytotoxins against M<sup>pro</sup>, RNA Replicase and Spike Protein of SARS-CoV-2 by Molecular Dynamics. Inspired by Nature |
| title_full_unstemmed | In Silico Evaluation of Sesquiterpenes and Benzoxazinoids Phytotoxins against M<sup>pro</sup>, RNA Replicase and Spike Protein of SARS-CoV-2 by Molecular Dynamics. Inspired by Nature |
| title_short | In Silico Evaluation of Sesquiterpenes and Benzoxazinoids Phytotoxins against M<sup>pro</sup>, RNA Replicase and Spike Protein of SARS-CoV-2 by Molecular Dynamics. Inspired by Nature |
| title_sort | in silico evaluation of sesquiterpenes and benzoxazinoids phytotoxins against m sup pro sup rna replicase and spike protein of sars cov 2 by molecular dynamics inspired by nature |
| topic | molecular dynamics docking SARS-CoV-2 COVID-19 sesquiterpene benzoxazinoid |
| url | https://www.mdpi.com/2072-6651/14/9/599 |
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