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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/21/11508 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T06:01:25Z |
| format | Article |
| id | doaj.art-2bb22b49e4aa49e3806b88ce407630ac |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T06:01:25Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2bb22b49e4aa49e3806b88ce407630ac2023-11-22T20:53:20ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-10-0122211150810.3390/ijms222111508Structural and Functional Analysis of Female Sex Hormones against SARS-CoV-2 Cell EntryJorge Alberto Aguilar-Pineda0Mazen Albaghdadi1Wanlin Jiang2Karin J. Vera-Lopez3Rita Nieto-Montesinos4Karla Lucia F. Alvarez5Gonzalo Davila Del-Carpio6Badhin Gómez7Mark E. Lindsay8Rajeev Malhotra9Christian L. Lino Cardenas10Laboratory of Genomics and Neurovascular Diseases, Vicerrectorado de Investigación, Universidad Católica de Santa María, Arequipa 04001, PeruCardiovascular Research Center, Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USACardiovascular Research Center, Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USALaboratory of Genomics and Neurovascular Diseases, Vicerrectorado de Investigación, Universidad Católica de Santa María, Arequipa 04001, PeruLaboratory of Genomics and Neurovascular Diseases, Vicerrectorado de Investigación, Universidad Católica de Santa María, Arequipa 04001, PeruLaboratory of Genomics and Neurovascular Diseases, Vicerrectorado de Investigación, Universidad Católica de Santa María, Arequipa 04001, PeruLaboratory of Genomics and Neurovascular Diseases, Vicerrectorado de Investigación, Universidad Católica de Santa María, Arequipa 04001, PeruLaboratory of Genomics and Neurovascular Diseases, Vicerrectorado de Investigación, Universidad Católica de Santa María, Arequipa 04001, PeruCardiovascular Research Center, Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USACardiovascular Research Center, Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USACardiovascular Research Center, Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USAEmerging 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.https://www.mdpi.com/1422-0067/22/21/11508COVID-19ACE2sex hormonesestrogenes |
| spellingShingle | 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 International Journal of Molecular Sciences COVID-19 ACE2 sex hormones estrogenes |
| title | 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_short | 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 |
| topic | COVID-19 ACE2 sex hormones estrogenes |
| url | https://www.mdpi.com/1422-0067/22/21/11508 |
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