While we wait for a vaccine against SARS-CoV-2, why not think about available drugs?

Autores
Barrantes, Francisco José
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Fil: Barrantes, Francisco José. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Barrantes, Francisco José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Abstract: At the time of reception of this article (April 2, 2020), efforts to develop a specific vaccine against SARS-Cov-2, the causative agent of the coronavirus disease 2019 (COVID-19), had just begun trial phase 1, but full validation of this and other current developments is likely to take many more months to reach completion. The ongoing pandemic constitutes a major health burden of world proportions that is also having a devastating impact on whole economies worldwide, the knock-on effects of which could be catastrophic especially in poorer countries. Alternative measures to ameliorate the impact and hamper or minimally slow down disease progression are urgently called for. This review discusses past and currently evolving data on the etiological agent of the current pandemic, SARS-CoV-2, and its host cell receptors with a view to disclosing alternative drugs for palliative or therapeutic approaches. Firstly, SARS-CoV-2 exhibits marked tropism for cells that harbor the membrane-bound metalloprotease angiotensin-converting enzyme 2 (ACE2) at their plasmalemma, predominantly in cells lining the oral cavity, upper respiratory tract, and bronchoalveolar cells, making these epithelial mucosae the most likely viral receptor cell targets and entry routes. Secondly, the crystal structures of several coronavirus spike proteins in complex with their cell host target receptors, and of SARS-Cov-2 in complex with an inhibitor, are now available at atomic resolution through X-ray diffraction and cryo-electron microscopy studies. Thirdly, viral entry of other viruses has been successfully blocked by inhibiting viral endogenous proteases or clathrin/dynamin-dependent endocytosis, the same internalization pathway followed by ACE2 and some viruses. Fourthly, the target cell-surface receptor molecules and SARS-CoV-2 possess other putative sites for drugs potentially modulating receptor activity or virus processing. A multi-pronged pharmacological approach attacking more than one flank of the viral-receptor interactions is worth considering as a front-line strategy.
Fuente
Frontiers in Physiology. 2020, 11:820
Materia
COVID-19
VACUNACION
PROFILAXIS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
Repositorio Institucional (UCA)
Institución
Pontificia Universidad Católica Argentina
OAI Identificador
oai:ucacris:123456789/14224

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network_name_str Repositorio Institucional (UCA)
spelling While we wait for a vaccine against SARS-CoV-2, why not think about available drugs?Barrantes, Francisco JoséCOVID-19VACUNACIONPROFILAXISFil: Barrantes, Francisco José. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; ArgentinaFil: Barrantes, Francisco José. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaAbstract: At the time of reception of this article (April 2, 2020), efforts to develop a specific vaccine against SARS-Cov-2, the causative agent of the coronavirus disease 2019 (COVID-19), had just begun trial phase 1, but full validation of this and other current developments is likely to take many more months to reach completion. The ongoing pandemic constitutes a major health burden of world proportions that is also having a devastating impact on whole economies worldwide, the knock-on effects of which could be catastrophic especially in poorer countries. Alternative measures to ameliorate the impact and hamper or minimally slow down disease progression are urgently called for. This review discusses past and currently evolving data on the etiological agent of the current pandemic, SARS-CoV-2, and its host cell receptors with a view to disclosing alternative drugs for palliative or therapeutic approaches. Firstly, SARS-CoV-2 exhibits marked tropism for cells that harbor the membrane-bound metalloprotease angiotensin-converting enzyme 2 (ACE2) at their plasmalemma, predominantly in cells lining the oral cavity, upper respiratory tract, and bronchoalveolar cells, making these epithelial mucosae the most likely viral receptor cell targets and entry routes. Secondly, the crystal structures of several coronavirus spike proteins in complex with their cell host target receptors, and of SARS-Cov-2 in complex with an inhibitor, are now available at atomic resolution through X-ray diffraction and cryo-electron microscopy studies. Thirdly, viral entry of other viruses has been successfully blocked by inhibiting viral endogenous proteases or clathrin/dynamin-dependent endocytosis, the same internalization pathway followed by ACE2 and some viruses. Fourthly, the target cell-surface receptor molecules and SARS-CoV-2 possess other putative sites for drugs potentially modulating receptor activity or virus processing. A multi-pronged pharmacological approach attacking more than one flank of the viral-receptor interactions is worth considering as a front-line strategy.Frontiers Media2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttps://repositorio.uca.edu.ar/handle/123456789/142241664-042X10.3389/fphys.2020.0082032719619Barrantes, F.J. While we wait for a vaccine against SARS-CoV-2, why not think about available drugs? [en línea]. Frontiers in Physiology. 2020, 11:820 doi:10.3389/fphys.2020.00820 Disponible en: https://repositorio.uca.edu.ar/handle/123456789/14224Frontiers in Physiology. 2020, 11:820reponame:Repositorio Institucional (UCA)instname:Pontificia Universidad Católica Argentinaenginfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/4.0/2025-07-03T10:58:38Zoai:ucacris:123456789/14224instacron:UCAInstitucionalhttps://repositorio.uca.edu.ar/Universidad privadaNo correspondehttps://repositorio.uca.edu.ar/oaiclaudia_fernandez@uca.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:25852025-07-03 10:58:38.329Repositorio Institucional (UCA) - Pontificia Universidad Católica Argentinafalse
dc.title.none.fl_str_mv While we wait for a vaccine against SARS-CoV-2, why not think about available drugs?
title While we wait for a vaccine against SARS-CoV-2, why not think about available drugs?
spellingShingle While we wait for a vaccine against SARS-CoV-2, why not think about available drugs?
Barrantes, Francisco José
COVID-19
VACUNACION
PROFILAXIS
title_short While we wait for a vaccine against SARS-CoV-2, why not think about available drugs?
title_full While we wait for a vaccine against SARS-CoV-2, why not think about available drugs?
title_fullStr While we wait for a vaccine against SARS-CoV-2, why not think about available drugs?
title_full_unstemmed While we wait for a vaccine against SARS-CoV-2, why not think about available drugs?
title_sort While we wait for a vaccine against SARS-CoV-2, why not think about available drugs?
dc.creator.none.fl_str_mv Barrantes, Francisco José
author Barrantes, Francisco José
author_facet Barrantes, Francisco José
author_role author
dc.subject.none.fl_str_mv COVID-19
VACUNACION
PROFILAXIS
topic COVID-19
VACUNACION
PROFILAXIS
dc.description.none.fl_txt_mv Fil: Barrantes, Francisco José. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Barrantes, Francisco José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Abstract: At the time of reception of this article (April 2, 2020), efforts to develop a specific vaccine against SARS-Cov-2, the causative agent of the coronavirus disease 2019 (COVID-19), had just begun trial phase 1, but full validation of this and other current developments is likely to take many more months to reach completion. The ongoing pandemic constitutes a major health burden of world proportions that is also having a devastating impact on whole economies worldwide, the knock-on effects of which could be catastrophic especially in poorer countries. Alternative measures to ameliorate the impact and hamper or minimally slow down disease progression are urgently called for. This review discusses past and currently evolving data on the etiological agent of the current pandemic, SARS-CoV-2, and its host cell receptors with a view to disclosing alternative drugs for palliative or therapeutic approaches. Firstly, SARS-CoV-2 exhibits marked tropism for cells that harbor the membrane-bound metalloprotease angiotensin-converting enzyme 2 (ACE2) at their plasmalemma, predominantly in cells lining the oral cavity, upper respiratory tract, and bronchoalveolar cells, making these epithelial mucosae the most likely viral receptor cell targets and entry routes. Secondly, the crystal structures of several coronavirus spike proteins in complex with their cell host target receptors, and of SARS-Cov-2 in complex with an inhibitor, are now available at atomic resolution through X-ray diffraction and cryo-electron microscopy studies. Thirdly, viral entry of other viruses has been successfully blocked by inhibiting viral endogenous proteases or clathrin/dynamin-dependent endocytosis, the same internalization pathway followed by ACE2 and some viruses. Fourthly, the target cell-surface receptor molecules and SARS-CoV-2 possess other putative sites for drugs potentially modulating receptor activity or virus processing. A multi-pronged pharmacological approach attacking more than one flank of the viral-receptor interactions is worth considering as a front-line strategy.
description Fil: Barrantes, Francisco José. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://repositorio.uca.edu.ar/handle/123456789/14224
1664-042X
10.3389/fphys.2020.00820
32719619
Barrantes, F.J. While we wait for a vaccine against SARS-CoV-2, why not think about available drugs? [en línea]. Frontiers in Physiology. 2020, 11:820 doi:10.3389/fphys.2020.00820 Disponible en: https://repositorio.uca.edu.ar/handle/123456789/14224
url https://repositorio.uca.edu.ar/handle/123456789/14224
identifier_str_mv 1664-042X
10.3389/fphys.2020.00820
32719619
Barrantes, F.J. While we wait for a vaccine against SARS-CoV-2, why not think about available drugs? [en línea]. Frontiers in Physiology. 2020, 11:820 doi:10.3389/fphys.2020.00820 Disponible en: https://repositorio.uca.edu.ar/handle/123456789/14224
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/4.0/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/4.0/
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv Frontiers in Physiology. 2020, 11:820
reponame:Repositorio Institucional (UCA)
instname:Pontificia Universidad Católica Argentina
reponame_str Repositorio Institucional (UCA)
collection Repositorio Institucional (UCA)
instname_str Pontificia Universidad Católica Argentina
repository.name.fl_str_mv Repositorio Institucional (UCA) - Pontificia Universidad Católica Argentina
repository.mail.fl_str_mv claudia_fernandez@uca.edu.ar
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