While we wait for a vaccine against SARS-CoV-2, why not think about available drugs?
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...
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| Formato: | Artículo |
| Lenguaje: | Inglés |
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Frontiers Media
2022
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| Acceso en línea: | https://repositorio.uca.edu.ar/handle/123456789/14224 |
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| Sumario: | 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. |
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