Características químicas, mecanismo de acción y actividad antiviral de etravirina
Chemical characteristics, mechanism of action and antiviral activity of etravirine
Federico García García
, Marta Álvarez Estévez, Vicente Guillot Suay
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Unidad de Microbiología Molecular, Servicio de Microbiología, Hospital Universitario San Cecilio, Granada, España
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Se trata de una molécula policíclica, constituida por 3 anillos aromáticos unidos por enlaces sencillos (C<span class="elsevierStyleInf">20</span>H<span class="elsevierStyleInf">15</span>BrN<span class="elsevierStyleInf">60</span>). Ejerce su acción mediante un mecanismo de inhibición no competitiva, al unirse a un bolsillo hidrofóbico <span class="elsevierStyleItalic">(binding pocket)</span>, muy cercano al centro activo de la enzima, provocando un cambio alostérico hacia una conformación que distorsiona su estructura e impide la polimerización del ADN. Al tratarse de 3 anillos unidos por enlaces sencillos, la molécula está dotada de una enorme fl exibilidad y capacidad de torsión. Debido a estas características, ETR puede “acomodarse” a cambios conformacionales en el <span class="elsevierStyleItalic">binding pocket</span>, incluidas un gran número de las conformaciones provocadas por las mutaciones de resistencia que aparecen tras el fracaso a regímenes que incluyen efavirenz o nevirapina. Esta particular estructura química explicará gran parte de sus peculiaridades y diferencias en cuanto a su potencia antiviral y su elevada barrera genética. ETR es una molécula muy activa frente a VIH-1. Presenta una elevada barrera genética y ha demostrado actividad antiviral frente a un amplio panel de virus recombinantes que incorporan mutaciones de resistencia a los no análogos de primera generación. De igual modo, ha demostrado ser eficaz frente a diversos subtipos del grupo M del virus de la inmunodeficiencia humana (VIH) 1 (A, B, C, D, F y H y formas recombinantes CRF01_AE, CRF02_AG, CRF05_ DF) y frente a aislados de VIH-1 grupo O. ETR, como el resto de no análogos, no ha demostrado actividad antiviral frente a VIH-2.</p>" ] "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<p class="elsevierStyleSimplePara elsevierViewall">Etravirine (ETR) is a diarylpyrimidine derivative with a polycyclic molecule composed of 3 aromatic rings with single bonds between the rings (C<span class="elsevierStyleInf">20</span>H<span class="elsevierStyleInf">15</span>BrN<span class="elsevierStyleInf">60</span>). The drug acts through a mechanism of noncompetitive inhibition on binding to a hydrophobic binding pocket, very close to the active center of the enzyme, provoking an allosteric transition to a conformation that distorts its structure and impedes DNA polymerization.</p><p class="elsevierStyleSimplePara elsevierViewall">The 3 rings with single bonds between the rings confer the molecule with great fl exibility and torsion. Because of these characteristics, etravirine can adapt to conformational changes in the binding pocket, including a large number of the conformations provoked by the resistance mutations that appear after failure to regimens that include efavirenz or nevirapine. This specific chemical structure largely explains the drug's distinguishing features in terms of its antiviral potency and high genetic barrier. ETR is a highly active molecule against HIV-1. This drug has a high genetic barrier to resistance and has demonstrated antiviral activity against a wide panel of recombinant viruses that incorporate resistance mutations to first-generation non-nucleoside analogues. Equally, ETR has demonstrated efficacy against several subtypes of the M group of HIV-1 (A, B, C, D, F and H, and recombinant forms CRF01_AE, CRF02_AG, CRF05_DF), as well as against isolates of HIV-1 group O. ETR, as the rest of non-nucleoside analogues, does not have demonstrated antiviral activity against HIV-2.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "Bibliografía" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:17 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Etravirine for the treatment of HIV infection" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "E. Seminari" 1 => "A. Castagna" 2 => "A. 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Nijs" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:3 [ "titulo" => "XVII HIV Drug Resistance Workshop" "conferencia" => "Sitges, Spain" "serieFecha" => "2008" ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib17" "etiqueta" => "17." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Raltegravir and etravirine are active against HIV type 1 group O" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "V. Briz" 1 => "C. Garrido" 2 => "E. Poveda" 3 => "J. Morello" 4 => "P. Barreiro" 5 => "C. De Mendoza" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1089/aid.2008.0222" "Revista" => array:6 [ "tituloSerie" => "AIDS Res Hum Retroviruses" "fecha" => "2009" "volumen" => "25" "paginaInicial" => "225" "paginaFinal" => "227" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19239363" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "es" "url" => "/0213005X/00000027000000S2/v1_201305090145/S0213005X09732124/v1_201305090145/es/main.assets" "Apartado" => null "PDF" => "https://static.elsevier.es/multimedia/0213005X/00000027000000S2/v1_201305090145/S0213005X09732124/v1_201305090145/es/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0213005X09732124?idApp=UINPBA00004N" ]
| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 1 | 0 | 1 |
| 2024 Octubre | 7 | 2 | 9 |
| 2024 Septiembre | 16 | 6 | 22 |
| 2024 Agosto | 9 | 4 | 13 |
| 2024 Julio | 9 | 8 | 17 |
| 2024 Junio | 8 | 5 | 13 |
| 2024 Mayo | 6 | 13 | 19 |
| 2024 Abril | 5 | 10 | 15 |
| 2024 Marzo | 12 | 8 | 20 |
| 2024 Febrero | 6 | 1 | 7 |
| 2024 Enero | 8 | 7 | 15 |
| 2023 Diciembre | 6 | 3 | 9 |
| 2023 Noviembre | 6 | 15 | 21 |
| 2023 Octubre | 7 | 16 | 23 |
| 2023 Septiembre | 15 | 4 | 19 |
| 2023 Agosto | 11 | 0 | 11 |
| 2023 Julio | 4 | 2 | 6 |
| 2023 Junio | 6 | 2 | 8 |
| 2023 Mayo | 10 | 2 | 12 |
| 2023 Abril | 9 | 0 | 9 |
| 2023 Marzo | 9 | 3 | 12 |
| 2023 Febrero | 5 | 5 | 10 |
| 2023 Enero | 13 | 3 | 16 |
| 2022 Diciembre | 17 | 4 | 21 |
| 2022 Noviembre | 14 | 7 | 21 |
| 2022 Octubre | 10 | 7 | 17 |
| 2022 Septiembre | 13 | 3 | 16 |
| 2022 Agosto | 10 | 5 | 15 |
| 2022 Julio | 11 | 8 | 19 |
| 2022 Junio | 12 | 8 | 20 |
| 2022 Mayo | 10 | 5 | 15 |
| 2022 Abril | 10 | 8 | 18 |
| 2022 Marzo | 21 | 9 | 30 |
| 2022 Febrero | 31 | 3 | 34 |
| 2022 Enero | 23 | 8 | 31 |
| 2021 Diciembre | 28 | 9 | 37 |
| 2021 Noviembre | 23 | 9 | 32 |
| 2021 Octubre | 26 | 12 | 38 |
| 2021 Septiembre | 14 | 8 | 22 |
| 2021 Agosto | 20 | 10 | 30 |
| 2021 Julio | 9 | 7 | 16 |
| 2021 Junio | 12 | 6 | 18 |
| 2021 Mayo | 10 | 11 | 21 |
| 2021 Abril | 10 | 19 | 29 |
| 2021 Marzo | 8 | 17 | 25 |
| 2021 Febrero | 8 | 10 | 18 |
| 2021 Enero | 8 | 10 | 18 |
| 2020 Diciembre | 9 | 11 | 20 |
| 2020 Noviembre | 12 | 3 | 15 |
| 2020 Octubre | 4 | 11 | 15 |
| 2020 Septiembre | 15 | 9 | 24 |
| 2020 Agosto | 16 | 7 | 23 |
| 2020 Julio | 11 | 7 | 18 |
| 2020 Junio | 9 | 6 | 15 |
| 2020 Mayo | 15 | 12 | 27 |
| 2020 Abril | 48 | 9 | 57 |
| 2020 Marzo | 26 | 11 | 37 |
| 2020 Febrero | 32 | 5 | 37 |
| 2020 Enero | 21 | 11 | 32 |
| 2019 Diciembre | 16 | 11 | 27 |
| 2019 Noviembre | 17 | 4 | 21 |
| 2019 Octubre | 13 | 6 | 19 |
| 2019 Septiembre | 16 | 7 | 23 |
| 2019 Agosto | 19 | 6 | 25 |
| 2019 Julio | 10 | 11 | 21 |
| 2019 Junio | 57 | 45 | 102 |
| 2019 Mayo | 114 | 69 | 183 |
| 2019 Abril | 34 | 37 | 71 |
| 2019 Marzo | 11 | 18 | 29 |
| 2019 Febrero | 15 | 23 | 38 |
| 2019 Enero | 7 | 23 | 30 |
| 2018 Diciembre | 6 | 6 | 12 |
| 2018 Noviembre | 11 | 11 | 22 |
| 2018 Octubre | 13 | 7 | 20 |
| 2018 Septiembre | 20 | 7 | 27 |
| 2018 Agosto | 4 | 4 | 8 |
| 2018 Julio | 8 | 9 | 17 |
| 2018 Junio | 6 | 14 | 20 |
| 2018 Mayo | 3 | 12 | 15 |
| 2018 Abril | 7 | 6 | 13 |
| 2018 Marzo | 2 | 4 | 6 |
| 2018 Febrero | 3 | 2 | 5 |
| 2018 Enero | 1 | 2 | 3 |
| 2017 Diciembre | 4 | 0 | 4 |
| 2017 Noviembre | 4 | 3 | 7 |
| 2017 Octubre | 5 | 5 | 10 |
| 2017 Septiembre | 7 | 6 | 13 |
| 2017 Agosto | 6 | 2 | 8 |
| 2017 Julio | 8 | 2 | 10 |
| 2017 Junio | 14 | 21 | 35 |
| 2017 Mayo | 27 | 5 | 32 |
| 2017 Abril | 13 | 3 | 16 |
| 2017 Marzo | 21 | 4 | 25 |
| 2017 Febrero | 22 | 2 | 24 |
| 2017 Enero | 20 | 2 | 22 |
| 2016 Diciembre | 28 | 4 | 32 |
| 2016 Noviembre | 30 | 5 | 35 |
| 2016 Octubre | 45 | 11 | 56 |
| 2016 Septiembre | 49 | 6 | 55 |
| 2016 Agosto | 25 | 8 | 33 |
| 2016 Julio | 17 | 3 | 20 |
| 2016 Junio | 17 | 7 | 24 |
| 2016 Mayo | 20 | 25 | 45 |
| 2016 Abril | 20 | 4 | 24 |
| 2016 Marzo | 17 | 10 | 27 |
| 2016 Febrero | 18 | 9 | 27 |
| 2016 Enero | 18 | 11 | 29 |
| 2015 Diciembre | 11 | 8 | 19 |
| 2015 Noviembre | 21 | 6 | 27 |
| 2015 Octubre | 20 | 11 | 31 |
| 2015 Septiembre | 17 | 7 | 24 |
| 2015 Agosto | 18 | 6 | 24 |
| 2015 Julio | 18 | 3 | 21 |
| 2015 Junio | 14 | 4 | 18 |
| 2015 Mayo | 11 | 1 | 12 |
| 2015 Abril | 12 | 3 | 15 |
| 2015 Marzo | 12 | 5 | 17 |
| 2015 Febrero | 9 | 5 | 14 |
| 2015 Enero | 25 | 6 | 31 |
| 2014 Diciembre | 28 | 6 | 34 |
| 2014 Noviembre | 22 | 1 | 23 |
| 2014 Octubre | 20 | 3 | 23 |
| 2014 Septiembre | 15 | 3 | 18 |
| 2014 Agosto | 22 | 2 | 24 |
| 2014 Julio | 21 | 1 | 22 |
| 2014 Junio | 34 | 4 | 38 |
| 2014 Mayo | 17 | 3 | 20 |
| 2014 Abril | 9 | 3 | 12 |
| 2014 Marzo | 23 | 3 | 26 |
| 2014 Febrero | 20 | 1 | 21 |
| 2014 Enero | 23 | 3 | 26 |
| 2013 Diciembre | 15 | 7 | 22 |
| 2013 Noviembre | 24 | 2 | 26 |
| 2013 Octubre | 21 | 3 | 24 |
| 2013 Septiembre | 14 | 3 | 17 |
| 2013 Agosto | 19 | 4 | 23 |
| 2013 Julio | 19 | 1 | 20 |
| 2009 Diciembre | 674 | 0 | 674 |
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