In-Silico Molecular Modeling Studies to Identify Novel Potential Inhibitors of HPV E6 Protein
The etiological agent of some anogenital tract cancers is infection with the high-risk human papillomavirus (HPV). Currently, prophylactic vaccines against HPV have been validated, but the presence of drug treatment directed against the infection and its oncogenic effects remain essential. Among the...
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MDPI AG
2022-09-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/10/9/1452 |
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| author | Moujane Soumia Halima Hajji Mohamed El Mzibri Filali Zegzouti Younes Bouachrine Mohammed Benlyas Mohamed Moualij Benaissa |
| author_facet | Moujane Soumia Halima Hajji Mohamed El Mzibri Filali Zegzouti Younes Bouachrine Mohammed Benlyas Mohamed Moualij Benaissa |
| author_sort | Moujane Soumia |
| collection | DOAJ |
| description | The etiological agent of some anogenital tract cancers is infection with the high-risk human papillomavirus (HPV). Currently, prophylactic vaccines against HPV have been validated, but the presence of drug treatment directed against the infection and its oncogenic effects remain essential. Among the best drug targets, viral oncoprotein E6 has been identified as a key factor in cell immortalization and tumor progression in HPV-positive cells. E6, through interaction with the cellular ubiquitin ligase E6AP, can promote the degradation of p53, a tumor suppressor protein. Therefore, suppression of the creation of the E6-E6AP complex is one of the essential strategies to inhibit the survival and proliferation of infected cells. In the present study, we proposed an in-silico approach for the discovery of small molecules with inhibitory activity on the E6-E6AP interaction. The first three compounds (F0679-0355, F33774-0275, and F3345-0326) were selected on the basis of virtual screening and prediction of the molecules’ ADMET properties and docking with E6 protein, these molecules were selected for further study by investigating their stability in the E6 complex and their inhibitory effect on the E6-E6AP interaction by molecular dynamics (MD) simulation. The identified molecules thus represent a good starting point for the development of anti-HPV drugs. |
| first_indexed | 2024-03-09T22:17:12Z |
| format | Article |
| id | doaj.art-5945eed73ea54c5f814c17c8cb2c6866 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-09T22:17:12Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-5945eed73ea54c5f814c17c8cb2c68662023-11-23T19:21:23ZengMDPI AGVaccines2076-393X2022-09-01109145210.3390/vaccines10091452In-Silico Molecular Modeling Studies to Identify Novel Potential Inhibitors of HPV E6 ProteinMoujane Soumia0Halima Hajji1Mohamed El Mzibri2Filali Zegzouti Younes3Bouachrine Mohammed4Benlyas Mohamed5Moualij Benaissa6Biochemistry of Natural Substances, Faculty of Science and Techniques, Moulay Ismail University, Errachdia 50003, MoroccoMolecular Chemistry and Natural Substances Laboratory, Faculty of Science, Moulay Ismail University, Meknes 52202, MoroccoBiology and Medical Research Unit, National Centre for Energy, Nuclear Sciences and Techniques (CNESTEN), Rabat 10001, MoroccoLABASE Laboratory, Faculty of Science of Meknes, Moulay Ismail University, Meknes 52202, MoroccoMolecular Chemistry and Natural Substances Laboratory, Faculty of Science, Moulay Ismail University, Meknes 52202, MoroccoBiochemistry of Natural Substances, Faculty of Science and Techniques, Moulay Ismail University, Errachdia 50003, MoroccoBiochemistry of Natural Substances, Faculty of Science and Techniques, Moulay Ismail University, Errachdia 50003, MoroccoThe etiological agent of some anogenital tract cancers is infection with the high-risk human papillomavirus (HPV). Currently, prophylactic vaccines against HPV have been validated, but the presence of drug treatment directed against the infection and its oncogenic effects remain essential. Among the best drug targets, viral oncoprotein E6 has been identified as a key factor in cell immortalization and tumor progression in HPV-positive cells. E6, through interaction with the cellular ubiquitin ligase E6AP, can promote the degradation of p53, a tumor suppressor protein. Therefore, suppression of the creation of the E6-E6AP complex is one of the essential strategies to inhibit the survival and proliferation of infected cells. In the present study, we proposed an in-silico approach for the discovery of small molecules with inhibitory activity on the E6-E6AP interaction. The first three compounds (F0679-0355, F33774-0275, and F3345-0326) were selected on the basis of virtual screening and prediction of the molecules’ ADMET properties and docking with E6 protein, these molecules were selected for further study by investigating their stability in the E6 complex and their inhibitory effect on the E6-E6AP interaction by molecular dynamics (MD) simulation. The identified molecules thus represent a good starting point for the development of anti-HPV drugs.https://www.mdpi.com/2076-393X/10/9/1452cervical cancerMD simulationsdockingvirtual screeningE6-E6APADMET properties |
| spellingShingle | Moujane Soumia Halima Hajji Mohamed El Mzibri Filali Zegzouti Younes Bouachrine Mohammed Benlyas Mohamed Moualij Benaissa In-Silico Molecular Modeling Studies to Identify Novel Potential Inhibitors of HPV E6 Protein Vaccines cervical cancer MD simulations docking virtual screening E6-E6AP ADMET properties |
| title | In-Silico Molecular Modeling Studies to Identify Novel Potential Inhibitors of HPV E6 Protein |
| title_full | In-Silico Molecular Modeling Studies to Identify Novel Potential Inhibitors of HPV E6 Protein |
| title_fullStr | In-Silico Molecular Modeling Studies to Identify Novel Potential Inhibitors of HPV E6 Protein |
| title_full_unstemmed | In-Silico Molecular Modeling Studies to Identify Novel Potential Inhibitors of HPV E6 Protein |
| title_short | In-Silico Molecular Modeling Studies to Identify Novel Potential Inhibitors of HPV E6 Protein |
| title_sort | in silico molecular modeling studies to identify novel potential inhibitors of hpv e6 protein |
| topic | cervical cancer MD simulations docking virtual screening E6-E6AP ADMET properties |
| url | https://www.mdpi.com/2076-393X/10/9/1452 |
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