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In Silico Screening of Drugs That Target Different Forms of E Protein for Potential Treatment of COVID-19
Recently the E protein of SARS-CoV-2 has become a very important target in the potential treatment of COVID-19 since it is known to regulate different stages of the viral cycle. There is biochemical evidence that E protein exists in two forms, as monomer and homopentamer. An in silico screening anal...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9958997/ https://www.ncbi.nlm.nih.gov/pubmed/37259437 http://dx.doi.org/10.3390/ph16020296 |
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author | Ramírez Salinas, Gema Lizbeth López Rincón, Alejandro García Machorro, Jazmín Correa Basurto, José Martínez Archundia, Marlet |
author_facet | Ramírez Salinas, Gema Lizbeth López Rincón, Alejandro García Machorro, Jazmín Correa Basurto, José Martínez Archundia, Marlet |
author_sort | Ramírez Salinas, Gema Lizbeth |
collection | PubMed |
description | Recently the E protein of SARS-CoV-2 has become a very important target in the potential treatment of COVID-19 since it is known to regulate different stages of the viral cycle. There is biochemical evidence that E protein exists in two forms, as monomer and homopentamer. An in silico screening analysis was carried out employing 5852 ligands (from Zinc databases), and performing an ADMET analysis, remaining a set of 2155 compounds. Furthermore, docking analysis was performed on specific sites and different forms of the E protein. From this study we could identify that the following ligands showed the highest binding affinity: nilotinib, dutasteride, irinotecan, saquinavir and alectinib. We carried out some molecular dynamics simulations and free energy MM–PBSA calculations of the protein–ligand complexes (with the mentioned ligands). Of worthy interest is that saquinavir, nilotinib and alectinib are also considered as a promising multitarget ligand because it seems to inhibit three targets, which play an important role in the viral cycle. On the other side, saquinavir was shown to be able to bind to E protein both in its monomeric as well as pentameric forms. Finally, further experimental assays are needed to probe our hypothesis derived from in silico studies. |
format | Online Article Text |
id | pubmed-9958997 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99589972023-02-26 In Silico Screening of Drugs That Target Different Forms of E Protein for Potential Treatment of COVID-19 Ramírez Salinas, Gema Lizbeth López Rincón, Alejandro García Machorro, Jazmín Correa Basurto, José Martínez Archundia, Marlet Pharmaceuticals (Basel) Article Recently the E protein of SARS-CoV-2 has become a very important target in the potential treatment of COVID-19 since it is known to regulate different stages of the viral cycle. There is biochemical evidence that E protein exists in two forms, as monomer and homopentamer. An in silico screening analysis was carried out employing 5852 ligands (from Zinc databases), and performing an ADMET analysis, remaining a set of 2155 compounds. Furthermore, docking analysis was performed on specific sites and different forms of the E protein. From this study we could identify that the following ligands showed the highest binding affinity: nilotinib, dutasteride, irinotecan, saquinavir and alectinib. We carried out some molecular dynamics simulations and free energy MM–PBSA calculations of the protein–ligand complexes (with the mentioned ligands). Of worthy interest is that saquinavir, nilotinib and alectinib are also considered as a promising multitarget ligand because it seems to inhibit three targets, which play an important role in the viral cycle. On the other side, saquinavir was shown to be able to bind to E protein both in its monomeric as well as pentameric forms. Finally, further experimental assays are needed to probe our hypothesis derived from in silico studies. MDPI 2023-02-14 /pmc/articles/PMC9958997/ /pubmed/37259437 http://dx.doi.org/10.3390/ph16020296 Text en © 2023 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 Ramírez Salinas, Gema Lizbeth López Rincón, Alejandro García Machorro, Jazmín Correa Basurto, José Martínez Archundia, Marlet In Silico Screening of Drugs That Target Different Forms of E Protein for Potential Treatment of COVID-19 |
title | In Silico Screening of Drugs That Target Different Forms of E Protein for Potential Treatment of COVID-19 |
title_full | In Silico Screening of Drugs That Target Different Forms of E Protein for Potential Treatment of COVID-19 |
title_fullStr | In Silico Screening of Drugs That Target Different Forms of E Protein for Potential Treatment of COVID-19 |
title_full_unstemmed | In Silico Screening of Drugs That Target Different Forms of E Protein for Potential Treatment of COVID-19 |
title_short | In Silico Screening of Drugs That Target Different Forms of E Protein for Potential Treatment of COVID-19 |
title_sort | in silico screening of drugs that target different forms of e protein for potential treatment of covid-19 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9958997/ https://www.ncbi.nlm.nih.gov/pubmed/37259437 http://dx.doi.org/10.3390/ph16020296 |
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