Prediction of potential inhibitors of SARS-CoV-2 using 3D-QSAR, molecular docking modeling and ADMET properties
Coronavirus (COVID-19), an enveloped RNA virus, primarily affects human beings. It has been deemed by the World Health Organization (WHO) as a pandemic. For this reason, COVID-19 has become one of the most lethal viruses which the modern world has ever witnessed although some established pharmaceuti...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-03-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844021007064 |
| _version_ | 1819088792940707840 |
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| author | Ayoub Khaldan Soukaina Bouamrane Fatima En-Nahli Reda El-mernissi Khalil El khatabi Rachid Hmamouchi Hamid Maghat Mohammed Aziz Ajana Abdelouahid Sbai Mohammed Bouachrine Tahar Lakhlifi |
| author_facet | Ayoub Khaldan Soukaina Bouamrane Fatima En-Nahli Reda El-mernissi Khalil El khatabi Rachid Hmamouchi Hamid Maghat Mohammed Aziz Ajana Abdelouahid Sbai Mohammed Bouachrine Tahar Lakhlifi |
| author_sort | Ayoub Khaldan |
| collection | DOAJ |
| description | Coronavirus (COVID-19), an enveloped RNA virus, primarily affects human beings. It has been deemed by the World Health Organization (WHO) as a pandemic. For this reason, COVID-19 has become one of the most lethal viruses which the modern world has ever witnessed although some established pharmaceutical companies allege that they have come up with a remedy for COVID-19. To that end, a set of carboxamides sulfonamide derivatives has been under study using 3D-QSAR approach. CoMFA and CoMSIA are one of the most cardinal techniques used in molecular modeling to mold a worthwhile 3D-QSAR model. The expected predictability has been achieved using the CoMFA model (Q2 = 0.579; R2 = 0.989; R2test = 0.791) and the CoMSIA model (Q2 = 0.542; R2 = 0.975; R2test = 0.964). In a similar vein, the contour maps extracted from both CoMFA and CoMSIA models provide much useful information to determine the structural requirements impacting the activity; subsequently, these contour maps pave the way for proposing 8 compounds with important predicted activities. The molecular surflex-docking simulation has been adopted to scrutinize the interactions existing between potentially and used antimalarial molecule on a large scale, called Chloroquine (CQ) and the proposed carboxamides sulfonamide analogs with COVID-19 main protease (PDB: 6LU7). The outcomes of the molecular docking point out that the new molecule P1 has high stability in the active site of COVID-19 and an efficient binding affinity (total scoring) in relation with the Chloroquine. Last of all, the newly designed carboxamides sulfonamide molecules have been evaluated for their oral bioavailability and toxicity, the results point out that these scaffolds have cardinal ADMET properties and can be granted as reliable inhibitors against COVID-19. |
| first_indexed | 2024-12-21T21:57:41Z |
| format | Article |
| id | doaj.art-8a6d5c27d1d14ca2940d66faf7ae6b17 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-12-21T21:57:41Z |
| publishDate | 2021-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-8a6d5c27d1d14ca2940d66faf7ae6b172022-12-21T18:48:55ZengElsevierHeliyon2405-84402021-03-0173e06603Prediction of potential inhibitors of SARS-CoV-2 using 3D-QSAR, molecular docking modeling and ADMET propertiesAyoub Khaldan0Soukaina Bouamrane1Fatima En-Nahli2Reda El-mernissi3Khalil El khatabi4Rachid Hmamouchi5Hamid Maghat6Mohammed Aziz Ajana7Abdelouahid Sbai8Mohammed Bouachrine9Tahar Lakhlifi10Molecular Chemistry and Natural Substances Laboratory, Faculty of Science, Moulay Ismail University of Meknes, MoroccoMolecular Chemistry and Natural Substances Laboratory, Faculty of Science, Moulay Ismail University of Meknes, MoroccoMolecular Chemistry and Natural Substances Laboratory, Faculty of Science, Moulay Ismail University of Meknes, MoroccoMolecular Chemistry and Natural Substances Laboratory, Faculty of Science, Moulay Ismail University of Meknes, MoroccoMolecular Chemistry and Natural Substances Laboratory, Faculty of Science, Moulay Ismail University of Meknes, MoroccoMolecular Chemistry and Natural Substances Laboratory, Faculty of Science, Moulay Ismail University of Meknes, MoroccoMolecular Chemistry and Natural Substances Laboratory, Faculty of Science, Moulay Ismail University of Meknes, MoroccoMolecular Chemistry and Natural Substances Laboratory, Faculty of Science, Moulay Ismail University of Meknes, MoroccoMolecular Chemistry and Natural Substances Laboratory, Faculty of Science, Moulay Ismail University of Meknes, Morocco; Corresponding author.Molecular Chemistry and Natural Substances Laboratory, Faculty of Science, Moulay Ismail University of Meknes, Morocco; EST Khenifra, Sultan Moulay Sliman University, Benimellal, MoroccoMolecular Chemistry and Natural Substances Laboratory, Faculty of Science, Moulay Ismail University of Meknes, MoroccoCoronavirus (COVID-19), an enveloped RNA virus, primarily affects human beings. It has been deemed by the World Health Organization (WHO) as a pandemic. For this reason, COVID-19 has become one of the most lethal viruses which the modern world has ever witnessed although some established pharmaceutical companies allege that they have come up with a remedy for COVID-19. To that end, a set of carboxamides sulfonamide derivatives has been under study using 3D-QSAR approach. CoMFA and CoMSIA are one of the most cardinal techniques used in molecular modeling to mold a worthwhile 3D-QSAR model. The expected predictability has been achieved using the CoMFA model (Q2 = 0.579; R2 = 0.989; R2test = 0.791) and the CoMSIA model (Q2 = 0.542; R2 = 0.975; R2test = 0.964). In a similar vein, the contour maps extracted from both CoMFA and CoMSIA models provide much useful information to determine the structural requirements impacting the activity; subsequently, these contour maps pave the way for proposing 8 compounds with important predicted activities. The molecular surflex-docking simulation has been adopted to scrutinize the interactions existing between potentially and used antimalarial molecule on a large scale, called Chloroquine (CQ) and the proposed carboxamides sulfonamide analogs with COVID-19 main protease (PDB: 6LU7). The outcomes of the molecular docking point out that the new molecule P1 has high stability in the active site of COVID-19 and an efficient binding affinity (total scoring) in relation with the Chloroquine. Last of all, the newly designed carboxamides sulfonamide molecules have been evaluated for their oral bioavailability and toxicity, the results point out that these scaffolds have cardinal ADMET properties and can be granted as reliable inhibitors against COVID-19.http://www.sciencedirect.com/science/article/pii/S2405844021007064SARS-CoV-23D-QSARCarboxamides sulfonamideMolecular dockingDrug discoveryIn silico ADMET |
| spellingShingle | Ayoub Khaldan Soukaina Bouamrane Fatima En-Nahli Reda El-mernissi Khalil El khatabi Rachid Hmamouchi Hamid Maghat Mohammed Aziz Ajana Abdelouahid Sbai Mohammed Bouachrine Tahar Lakhlifi Prediction of potential inhibitors of SARS-CoV-2 using 3D-QSAR, molecular docking modeling and ADMET properties Heliyon SARS-CoV-2 3D-QSAR Carboxamides sulfonamide Molecular docking Drug discovery In silico ADMET |
| title | Prediction of potential inhibitors of SARS-CoV-2 using 3D-QSAR, molecular docking modeling and ADMET properties |
| title_full | Prediction of potential inhibitors of SARS-CoV-2 using 3D-QSAR, molecular docking modeling and ADMET properties |
| title_fullStr | Prediction of potential inhibitors of SARS-CoV-2 using 3D-QSAR, molecular docking modeling and ADMET properties |
| title_full_unstemmed | Prediction of potential inhibitors of SARS-CoV-2 using 3D-QSAR, molecular docking modeling and ADMET properties |
| title_short | Prediction of potential inhibitors of SARS-CoV-2 using 3D-QSAR, molecular docking modeling and ADMET properties |
| title_sort | prediction of potential inhibitors of sars cov 2 using 3d qsar molecular docking modeling and admet properties |
| topic | SARS-CoV-2 3D-QSAR Carboxamides sulfonamide Molecular docking Drug discovery In silico ADMET |
| url | http://www.sciencedirect.com/science/article/pii/S2405844021007064 |
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