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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9505724/ https://www.ncbi.nlm.nih.gov/pubmed/36146532 http://dx.doi.org/10.3390/vaccines10091452 |
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author | Soumia, Moujane Hajji, Halima El Mzibri, Mohamed Younes, Filali Zegzouti Mohammed, Bouachrine Mohamed, Benlyas Benaissa, Moualij |
author_facet | Soumia, Moujane Hajji, Halima El Mzibri, Mohamed Younes, Filali Zegzouti Mohammed, Bouachrine Mohamed, Benlyas Benaissa, Moualij |
author_sort | Soumia, Moujane |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-9505724 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-95057242022-09-24 In-Silico Molecular Modeling Studies to Identify Novel Potential Inhibitors of HPV E6 Protein Soumia, Moujane Hajji, Halima El Mzibri, Mohamed Younes, Filali Zegzouti Mohammed, Bouachrine Mohamed, Benlyas Benaissa, Moualij Vaccines (Basel) Article 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. MDPI 2022-09-02 /pmc/articles/PMC9505724/ /pubmed/36146532 http://dx.doi.org/10.3390/vaccines10091452 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Soumia, Moujane Hajji, Halima El Mzibri, Mohamed Younes, Filali Zegzouti Mohammed, Bouachrine Mohamed, Benlyas Benaissa, Moualij In-Silico Molecular Modeling Studies to Identify Novel Potential Inhibitors of HPV E6 Protein |
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 | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9505724/ https://www.ncbi.nlm.nih.gov/pubmed/36146532 http://dx.doi.org/10.3390/vaccines10091452 |
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