Structural and Functional Analysis of Female Sex Hormones against SARS-CoV-2 Cell Entry

Emerging evidence suggests that males are more susceptible to severe infection by the SARS-CoV-2 virus than females. A variety of mechanisms may underlie the observed gender-related disparities including differences in sex hormones. However, the precise mechanisms by which female sex hormones may pr...

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Autores principales:	Jorge Alberto Aguilar-Pineda, Mazen Albaghdadi, Wanlin Jiang, Karin J. Vera-Lopez, Rita Nieto-Montesinos, Karla Lucia F. Alvarez, Gonzalo Davila Del-Carpio, Badhin Gómez, Mark E. Lindsay, Rajeev Malhotra, Christian L. Lino Cardenas
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	COVID-19 ACE2 sex hormones estrogenes Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/2bb22b49e4aa49e3806b88ce407630ac
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spelling	oai:doaj.org-article:2bb22b49e4aa49e3806b88ce407630ac2021-11-11T16:58:14ZStructural and Functional Analysis of Female Sex Hormones against SARS-CoV-2 Cell Entry10.3390/ijms2221115081422-00671661-6596https://doaj.org/article/2bb22b49e4aa49e3806b88ce407630ac2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11508https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Emerging evidence suggests that males are more susceptible to severe infection by the SARS-CoV-2 virus than females. A variety of mechanisms may underlie the observed gender-related disparities including differences in sex hormones. However, the precise mechanisms by which female sex hormones may provide protection against SARS-CoV-2 infectivity remains unknown. Here we report new insights into the molecular basis of the interactions between the SARS-CoV-2 spike (S) protein and the human ACE2 receptor. We further report that glycosylation of the ACE2 receptor enhances SARS-CoV-2 infectivity. Importantly, estrogens can disrupt glycan–glycan interactions and glycan–protein interactions between the human ACE2 and the SARS-CoV-2 thereby blocking its entry into cells. In a mouse model of COVID-19, estrogens reduced ACE2 glycosylation and thereby alveolar uptake of the SARS-CoV-2 spike protein. These results shed light on a putative mechanism whereby female sex hormones may provide protection from developing severe infection and could inform the development of future therapies against COVID-19.Jorge Alberto Aguilar-PinedaMazen AlbaghdadiWanlin JiangKarin J. Vera-LopezRita Nieto-MontesinosKarla Lucia F. AlvarezGonzalo Davila Del-CarpioBadhin GómezMark E. LindsayRajeev MalhotraChristian L. Lino CardenasMDPI AGarticleCOVID-19ACE2sex hormonesestrogenesBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11508, p 11508 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	COVID-19 ACE2 sex hormones estrogenes Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	COVID-19 ACE2 sex hormones estrogenes Biology (General) QH301-705.5 Chemistry QD1-999 Jorge Alberto Aguilar-Pineda Mazen Albaghdadi Wanlin Jiang Karin J. Vera-Lopez Rita Nieto-Montesinos Karla Lucia F. Alvarez Gonzalo Davila Del-Carpio Badhin Gómez Mark E. Lindsay Rajeev Malhotra Christian L. Lino Cardenas Structural and Functional Analysis of Female Sex Hormones against SARS-CoV-2 Cell Entry
description	Emerging evidence suggests that males are more susceptible to severe infection by the SARS-CoV-2 virus than females. A variety of mechanisms may underlie the observed gender-related disparities including differences in sex hormones. However, the precise mechanisms by which female sex hormones may provide protection against SARS-CoV-2 infectivity remains unknown. Here we report new insights into the molecular basis of the interactions between the SARS-CoV-2 spike (S) protein and the human ACE2 receptor. We further report that glycosylation of the ACE2 receptor enhances SARS-CoV-2 infectivity. Importantly, estrogens can disrupt glycan–glycan interactions and glycan–protein interactions between the human ACE2 and the SARS-CoV-2 thereby blocking its entry into cells. In a mouse model of COVID-19, estrogens reduced ACE2 glycosylation and thereby alveolar uptake of the SARS-CoV-2 spike protein. These results shed light on a putative mechanism whereby female sex hormones may provide protection from developing severe infection and could inform the development of future therapies against COVID-19.
format	article
author	Jorge Alberto Aguilar-Pineda Mazen Albaghdadi Wanlin Jiang Karin J. Vera-Lopez Rita Nieto-Montesinos Karla Lucia F. Alvarez Gonzalo Davila Del-Carpio Badhin Gómez Mark E. Lindsay Rajeev Malhotra Christian L. Lino Cardenas
author_facet	Jorge Alberto Aguilar-Pineda Mazen Albaghdadi Wanlin Jiang Karin J. Vera-Lopez Rita Nieto-Montesinos Karla Lucia F. Alvarez Gonzalo Davila Del-Carpio Badhin Gómez Mark E. Lindsay Rajeev Malhotra Christian L. Lino Cardenas
author_sort	Jorge Alberto Aguilar-Pineda
title	Structural and Functional Analysis of Female Sex Hormones against SARS-CoV-2 Cell Entry
title_short	Structural and Functional Analysis of Female Sex Hormones against SARS-CoV-2 Cell Entry
title_full	Structural and Functional Analysis of Female Sex Hormones against SARS-CoV-2 Cell Entry
title_fullStr	Structural and Functional Analysis of Female Sex Hormones against SARS-CoV-2 Cell Entry
title_full_unstemmed	Structural and Functional Analysis of Female Sex Hormones against SARS-CoV-2 Cell Entry
title_sort	structural and functional analysis of female sex hormones against sars-cov-2 cell entry
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/2bb22b49e4aa49e3806b88ce407630ac
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Structural and Functional Analysis of Female Sex Hormones against SARS-CoV-2 Cell Entry

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