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Identification of host receptors for viral entry and beyond: a perspective from the spike of SARS-CoV-2

Identification of the interaction between the host membrane receptor and viral receptor-binding domain (RBD) represents a crucial step for understanding viral pathophysiology and for developing drugs against pathogenic viruses. While all membrane receptors and carbohydrate chains could potentially b...

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Autor principal: Xia, Xuhua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10407229/
https://www.ncbi.nlm.nih.gov/pubmed/37560522
http://dx.doi.org/10.3389/fmicb.2023.1188249
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author Xia, Xuhua
author_facet Xia, Xuhua
author_sort Xia, Xuhua
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description Identification of the interaction between the host membrane receptor and viral receptor-binding domain (RBD) represents a crucial step for understanding viral pathophysiology and for developing drugs against pathogenic viruses. While all membrane receptors and carbohydrate chains could potentially be used as receptors for viruses, prioritized searches focus typically on membrane receptors that are known to have been used by the relatives of the pathogenic virus, e.g., ACE2 used as a receptor for SARS-CoV is a prioritized candidate receptor for SARS-CoV-2. An ideal receptor protein from a viral perspective is one that is highly expressed in epithelial cell surface of mammalian respiratory or digestive tracts, strongly conserved in evolution so many mammalian species can serve as potential hosts, and functionally important so that its expression cannot be readily downregulated by the host in response to the infection. Experimental confirmation of host receptors includes (1) infection studies with cell cultures/tissues/organs with or without candidate receptor expression, (2) experimental determination of protein structure of the complex between the putative viral RDB and the candidate host receptor, and (3) experiments with mutant candidate receptor or homologues of the candidate receptor in other species. Successful identification of the host receptor opens the door for mechanism-based development of candidate drugs and vaccines and facilitates the inference of what other animal species are vulnerable to the viral pathogen. I illustrate these approaches with research on identification of the receptor and co-factors for SARS-CoV-2.
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spelling pubmed-104072292023-08-09 Identification of host receptors for viral entry and beyond: a perspective from the spike of SARS-CoV-2 Xia, Xuhua Front Microbiol Microbiology Identification of the interaction between the host membrane receptor and viral receptor-binding domain (RBD) represents a crucial step for understanding viral pathophysiology and for developing drugs against pathogenic viruses. While all membrane receptors and carbohydrate chains could potentially be used as receptors for viruses, prioritized searches focus typically on membrane receptors that are known to have been used by the relatives of the pathogenic virus, e.g., ACE2 used as a receptor for SARS-CoV is a prioritized candidate receptor for SARS-CoV-2. An ideal receptor protein from a viral perspective is one that is highly expressed in epithelial cell surface of mammalian respiratory or digestive tracts, strongly conserved in evolution so many mammalian species can serve as potential hosts, and functionally important so that its expression cannot be readily downregulated by the host in response to the infection. Experimental confirmation of host receptors includes (1) infection studies with cell cultures/tissues/organs with or without candidate receptor expression, (2) experimental determination of protein structure of the complex between the putative viral RDB and the candidate host receptor, and (3) experiments with mutant candidate receptor or homologues of the candidate receptor in other species. Successful identification of the host receptor opens the door for mechanism-based development of candidate drugs and vaccines and facilitates the inference of what other animal species are vulnerable to the viral pathogen. I illustrate these approaches with research on identification of the receptor and co-factors for SARS-CoV-2. Frontiers Media S.A. 2023-07-25 /pmc/articles/PMC10407229/ /pubmed/37560522 http://dx.doi.org/10.3389/fmicb.2023.1188249 Text en Copyright © 2023 Xia. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Xia, Xuhua
Identification of host receptors for viral entry and beyond: a perspective from the spike of SARS-CoV-2
title Identification of host receptors for viral entry and beyond: a perspective from the spike of SARS-CoV-2
title_full Identification of host receptors for viral entry and beyond: a perspective from the spike of SARS-CoV-2
title_fullStr Identification of host receptors for viral entry and beyond: a perspective from the spike of SARS-CoV-2
title_full_unstemmed Identification of host receptors for viral entry and beyond: a perspective from the spike of SARS-CoV-2
title_short Identification of host receptors for viral entry and beyond: a perspective from the spike of SARS-CoV-2
title_sort identification of host receptors for viral entry and beyond: a perspective from the spike of sars-cov-2
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10407229/
https://www.ncbi.nlm.nih.gov/pubmed/37560522
http://dx.doi.org/10.3389/fmicb.2023.1188249
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